Pharmacy Practice News - March 2022 by McMahon Group

The Best-Read Pharmacist’s News Source

pharmacypracticenews.com

OPERATIONS & MGMT

TJC: hospitals still tripping over titration orders ...................................

ASHP acts on burnout, certification ........................ 6 CLINICAL

Cracks in COVID-19 trials still showing ........

Opioid use disorder doesn’t have to be an emergency ......................

Ignoring a common cause of rabies proves deadly ...............

POLICY

Why are we not still billing for drug waste? ...............................

Can CAR T-Cell Rx Be Moved Outside Hospital?

The ‘OG’ Women of Specialty Pharmacy

By Gina Shaw

How a cadre of visionary female leaders broke through the market’s glass ceiling

lthough most people who are prescribed chimeric antigen receptor (CAR) T-cell therapy receive it entirely as inpatients, there is growing interest in delivering at least part of the revolutionary treatment in the outpatient setting. One major factor is reimbursement. As the revenue cycle team knows, payment terms often are more favorable when medications are administered outside the hospital. But it’s not just about money, according to Mary McGann, PharmD, BCOP, a clinical pharmacy specialist in blood and marrow transplantation and cellular therapy at the Hollings Cancer Center, Medical University of South Carolina (MUSC), in Charleston. Several other benefits have boosted interest in outpatient CAR T-cell

New CAR-T Data, Other Lymphoma Therapy Insights

ompeting in the specialty pharmacy space is no easy task, given its intensive data reporting requirements, cold chain logistics and closed-door payor contracts, to name just a few challenges. But if you were a female pharmacy leader eyeing market entry in the early days, there was yet another roadblock to overcome: a traditionally maledominated business that didn’t always embrace the idea that women belonged in the specialty space. Thanks to the efforts of a cadre of visionary female leaders, those barriers are not nearly as iron-clad as in years past. Indeed, these pioLeft to right: Rebecca Anguiano, PharmD (seated), neers have helped build highly sucpharmacy technician Elba Sertuche, Nehrin Khamo, cessful health-system specialty PharmD, and JoAnn Stubbings, BSPharm.

Continued on page 8

Software a Big Time-Saver In Drug Diversion Detection By Adam Leitenberger

By Ted Bosworth

Parenteral Nutrition Therapy See insert after page 16.

Pharmacist’s Role in the Management of Chronic GVHD See insert after page 24.

n advanced forms of lymphoma, a barrage of new data with chimeric antigen receptor (CAR) T cells was presented at the 2021 annual meeting of the American Society of Hematology (ASH), offering clinicians key guidance on safety and efficacy. Coupled with new findings on promising new “off-the-shelf,” allogeneic targeted agents that avoid some of the logistical challenges of obtaining autologous CAR T cells for infusions, the ASH meeting yielded important information for guiding Continued on page 16

By Gina Shaw

Continued on page 18

REVIEW ARTICLES

Volume 49 • Number 3 • March 2022

software-based analytics tool that enhances monitoring and auditing improved the effectiveness of a healthcare system’s drug diversion surveillance program, according to a presentation at the ASHP 2021 Midyear Clinical Meeting and Exhibition, held virtually. Within six months, the application led to an increase in document reconciliation and significant reductions in time spent to complete audits and investigations, JoAnne Myhre, CPhT, FMSHP, the drug diversion program manager at Allina Health System in Minneapolis, and her colleagues reported. “With this new automated documentation audit process, our staff can now focus on

Focus On

Oncology More coverage begins on page 17.

potential practice concerns sooner, because they are not spending time analyzing data and looking for the issues,” Ms. Myhre told Pharmacy Practice News. “The issues are now presented to them, whereas before they had to spend time analyzing the data, performing manual audits and then collating the data to try and see the anomalies.” Having such a tool on hand is an important advance, given the serious hazards drug diversion poses to patients, hospital staff and the general public, Ms. Myrhe noted. She added that the illegal activity also carries potential liability and financial risks for hospital systems. For example, patients may have inadequate pain relief if their prescribed opioids Continued on page 26

True containment. True comfort. Right in the palm of your hand. True drug containment that offers comfort and peace of mind, HALO® CSTD is your complete solution for hazardous drug preparation and administration. • Airtight and Leak-proof1 • Ergonomically designed for hand comfort2 • Strong and secure attachment3 • No internal ﬁlter to maximize vial extraction4 Make the HALO system your standard of care for enhanced protection of patients and caregivers. To request a demonstration or to order the HALO System, call 1-888-386-1300 or visit us at www.HALO-CSTD.com.

Your Containment and Protection Ally

HALO® is a registered trademark of Corvida Medical, Inc.

1. Health and Human Services, Federal Drug Administration, 510(k) Clearance Letter, July 24, 2015. 2. Ergonomics: The Study of Work. U.S. Department of Labor Occupational Safety and Health Administration. OSHA 3125 2000 (Revised). 3. Internal study, data on ﬁle. 4. Internal study, data on ﬁle.

Up Front

Pharmacy Practice News • March 2022

Digital

Liked/

CORRECTION

Retweeted

@PharmPracNews

In the article, “Time to Switch to Race-Free eGFR Renal Test?,” which appeared on page 1 of the February 2022 issue, there is an error in a sentence describing the history of eGFR equations. The sentence should have read as follows: According to Dr. St. Peter, the problem of race in kidney disease evaluation goes back for decades. The first eGFR equation—the Cockcroft-Gault equation— was developed in 1976 using a homogeneously white population, leading the equation to overestimate measured GFR in Blacks, when total body weight is used in the equation. We apologize for the error.

Video Exclusive

Sign up for our e-Newsletters! To receive breaking news, multimedia content and PPN digital editions, sign up for our twice-weekly e-Newsletter at pharmacypracticenews.com/ Registration.

Lisa Yamagishi, BS, PharmD, BCPS, CTTS, a clinical pharmacist—opioid stewardship, discusses a pharmacy-led program to increase the distribution of naloxone to patients at discharge from NYC Health + Hospitals|Kings County, in Brooklyn, NY. Watch the video at www.pharmacypracticenews.com/Multimedia

EDITORIAL BOARD ADMINISTRATION Robert Adamson, PharmD, Livingston, NJ

2021 Silver Award Winner

ART/PRODUCTION STAFF

How-to Feature

Frank Tagarello, Senior Art Director/Managing Director MAX Graphics

James A. Jorgenson, MS, RPh, St. Paul, MN

Volume 49 • Number 3 • March 2022 • pharmacypracticenews.com

Indu Lew, PharmD, Livingston, NJ

Michele McMahon Velle, MAX Graphics/Creative Director

James O’Neill, Senior Systems Manager Marty Barbieri, Associate Director of Production

AMBULATORY CARE Meghan D. Swarthout, PharmD, MBA, BCPS, Sallston, MD ANESTHESIOLOGY/PAIN Julie A. Golembiewski, PharmD, Chicago, IL

NUTRITION Beverly Holcombe, PharmD, BCNSP, FASHP, FASPEN Chapel Hill, NC

EDITORIAL STAFF

Leona Smith, Production Associate

David Bronstein, Editorial Director davidb@mcmahonmed.com

Rob Sinclair, Circulation Manager

Marie Rosenthal, MS, Senior Editor mrosenthal@mcmahonmed.com

Van Velle, President, Partner

McMAHON PUBLISHING

Vanessa Kumpf, PharmD, BCNSP, Nashville, TN

David S. Craig, PharmD, BCPS, Tampa, FL

ONCOLOGY Cindy O’Bryant, PharmD, Aurora, CO

Robert L. Barkin, MBA, PharmD, Chicago, IL CARDIOLOGY C. Michael White, PharmD, Storrs, CT

Lisa Holle, PharmD, Farmington, CT

Matthew McMahon, General Manager, Partner Lauren Smith, Michael McMahon, Michele McMahon Velle, Partners

Dave Doolittle, Associate Editor ddoolittle@mcmahonmed.com

Ali McBride, PharmD, MS, BCPS, Phoenix, AZ

CNS/PSYCHIATRY Lawrence Cohen, PharmD, FASHP, FCCP, Fort Worth, TX COMPLEMENTARY AND ALTERNATIVE MEDICINE Cathy Rosenbaum, PharmD, Cincinnati, OH CRITICAL CARE Judi Jacobi, PharmD, FCCM, Indianapolis, IN

Sara S. Kim, PharmD, BCOP, New York, NY

Kevin Horty, Don Pizzi Contributing Editors

ORGAN TRANSPLANT PHARMACY Eric Tichy, PharmD, BCPS, Rochester, MN

James Prudden, Group Editorial Director

PEDIATRICS Gretchen Brummel, PharmD, BCPS, Hudson, OH

Ray and Rosanne McMahon, Co-founders

THE McMAHON GROUP, LLC McMAHON PUBLISHING, McMAHONMED.COM Sales, Production and Editorial Offices: 545 West 45th Street, 8th Floor, New York, NY 10036 Telephone: (212) 957-5300 CT Office: 83 Peaceable Street, Redding, CT 06896

Elizabeth Zhong, Senior Copy Editor Kristin Jannacone, Copy Editor

PHARMACOGENOMICS Henry “Mark” Dunnenberger, PharmD, Evanston, IL

SALES

REIMBURSEMENT Bonnie E. Kirschenbaum, MS, FASHP, Breckenridge, CO

David Kaplan, Group Publication Director dkaplan@mcmahonmed.com

SPECIALTY PHARMACY JoAnn Stubbings, BSPharm, MHCA, Chicago, IL

Sarah Rezvani, Account Manager srezvani@mcmahonmed.com

Elaine Strauss, PharmD, MS, Atlanta, GA

STERILE COMPOUNDING Kristina N. Bryowsky, PharmD, MBA, BCPS, Fenton, MO

Joe Malichio, Director, Medical Education jmalichio@mcmahonmed.com

NUCLEAR PHARMACY Jeffrey Norenberg, PharmD, Albuquerque, NM

TECHNOLOGY Thomas Van Hassel, RPh, Yuma, AZ

Craig Wilson, Sales Associate, Classified Advertising cwilson@mcmahonmed.com

INFECTIOUS DISEASES Steven J. Martin, PharmD, BCPS, FCCM, Toledo, OH David P. Nicolau, PharmD, Hartford, CT Jason Pogue, PharmD, Detroit, MI LEADERSHIP Ernest R. Anderson Jr., MS, RPh, Boston, MA

WANT TO SUBSCRIBE? CHANGE YOUR ADDRESS? HERE’S HOW Selected U.S. hospital pharmacists and healthcare personnel receive Pharmacy Practice News free of charge. If you are a hospital pharmacist and do not receive the publication, you must add your professional address or make your address change directly with Pharmacy Practice News Circulation Dept., 545 W. 45th St.,

A family-owned medical publishing and medical education company. McMahon publishes seven clinical newspapers and several annual or semiannual Special Editions.

8th Floor, New York, NY 10036. You can also fax your request to (815) 366–8297, or send it via email, circulation@mcmahonmed.com. If you are not a hospital pharmacist but would like to receive Pharmacy Practice News, please send a check for $105.00 (U.S.) or $130.00 (outside U.S.) for a year’s subscription payable to Pharmacy Practice News to McMahon Publishing, 545 West 45th St., 8th

Copyright © 2022 McMahon Publishing, New York, NY 10036. All rights reserved. Pharmacy Practice News (ISSN 0886-988x) is published monthly by McMahon Publishing. Periodicals postage paid at New York, NY, and at additional mailing offices. POSTMASTER: Send address changes to Pharmacy Practice News, Circulation Dept., 545 W. 45th St., 8th Floor, New York, NY 10036. We endeavor to obtain relevant financial disclosures from all interviewees and rely on our sources to accurately provide this information.

Floor, New York, NY 10036. Please allow 8 to 12 weeks for delivery of the first issue. Individual issues are $10.00 (U.S.) or $13.00 (outside U.S.). Founded in 1972, McMahon Publishing is a family-owned medical publisher of clinical newspapers and specialty periodicals, and creates continuing medical education programs and custom publications.

4 Operations & Management

Pharmacy Practice News • March 2022

Management Compliance

TJC: Titrated Medications a Common Challenge By David Wild

any health systems still struggle to fully comply with a number of the Joint Commission’s medication management standards, particularly creating and following titration orders, according to the organization’s most recent survey results. “If you look at many of the top-scored standards [in terms of noncompliance], you will see that a lot of these revolve around medication orders,” Jeannell Mansur, RPh, PharmD, a principal consultant for Joint Commission Resources, said during a session at the ASHP 2021 Midyear Clinical Meeting and Exhibition, held virtually. “Creation of proper medication orders, as well as their interpretation and review, always comes up.” Dr. Mansur presented results from Joint Commission surveys of 1,355 institutions performed between January 2020 and September 2021. The most common area of noncompliance noted in the surveys involved administering a medication according to the prescriber order (49%; MM.06.01.01 Element of Performance [EP]3), the results showed. Following complex titration orders was a common cause of disparity between orders and administration, Dr. Mansur said. In addition, 15% of institutions did not have written policies defining minimal elements of a medication order, including medication titration orders (MM.04.01.01 EP2). The Joint Commission requires organizational policies to define which medications can be titrated, what the starting and maximum rates of infusion should be, incremental units by which the rate can be increased and decreased, the maximum frequency of infusion rate changes, the maximum infusion dose, and objective clinical and physiologic measures to guide changes. Although the onus is on nurses to follow orders as written, “organizations might want to make sure their titration orders reflect how specific medications are typically titrated and that they align with their own written policies,” Dr. Mansur said. “Titration of medications is a complex process in critically ill patients, and often the provider will provide the details of how much and how often dosing changes are made,” Dr. Mansur added. “But surveyors have found that nurses make changes to titrated medications that are not consistent with the order because the orders don’t reflect the needs of a patient care situation.”

Balancing Order Requirements With Patient Needs Don Janczak, PharmD, a consultant with Joint Commission Resources, told

session attendees there is a particular challenge for nurses, who have to juggle “managing these complex therapies, documenting changes and, at the same time, focusing on the care of the patient.” To provide nurses with the latitude to balance order requirements with patient care, the Joint Commission permits institutions to add certain features to titration orders, he said. For example, block charting allows nurses to document multiple dosing changes made during a defined period. (The Joint Commission specifies a maximum four-hour block.)

determine the administration of titratable drugs during the charting block. “Organizational policies should also specify where to document the charting episode, whether it’s in the medication administration record, in progress notes or through other EHR [electronic health record] options,” Dr. Janczak said. “Importantly, make sure not only that your policies have these key requirements but that you take this information from your policies and implement them in your medication-use process,” he stressed, noting that surveyors compare

they verify the order, it makes sense to them. Then you need to provide nurse education on the new protocols,” said Dr. White, who was not involved in the ASHP presentation. “It can be difficult to get everyone in the same room to work this out, and at times it feels like it is easier to work within their silo. But a team effort is really necessary to successfully implement complex orders.” Including titration parameters directly in her organization’s EHR order sets has helped ensure nurse practice is in compliance with organizational policy, particularly during the

‘Every single Joint Commission standard addresses a safety necessity and focuses on how to prevent errors, particularly in scenarios such as administration of complex orders and high-risk medications where an error can cause significant patient harm.’ —Jessalynn White, PharmD

Block charting can help nurses focus on making rapid infusion changes and choosing medications “in those critical moments when a patient may be hemodynamically unstable,” Dr. Janczak said. Organizations that allow block charting need to define the maximum charting period, the settings in which it can be done (critical care or procedural, as defined by the Joint Commission) and the allowable medications (limited to titrated vasoactive, titrated pain and titrated sedative medication infusions, as per the Joint Commission), he said. Written organizational policy should also specify the minimum elements required for each block-charting episode, Dr. Janczak said. As laid out by the Joint Commission, that includes: • the time of chart-blocking initiation and completion; • the name of the medications administered during the block; • the starting and ending rates of these medications; • the maximum rate and dose of these medications; and • physiologic parameters evaluated to

organizational titration order policy with what is in electronic order sets. Written policy should also specify what to do if a titrated IV infusion is paused and then requires restarting, Dr. Janczak said, adding that “it’s OK for the nurse to pause an infusion, but if it needs to be restarted based on assessment of a set of physiological parameters, the physician order must specify how to restart that infusion, including the starting dose and rate.”

‘A Team Effort Is Really Necessary’ Titration orders present yet another challenge: Creating and implementing them—and ensuring nurses comply— requires multidisciplinary buy-in from physicians, pharmacists and nurses, Jessalynn White, PharmD, the network medication safety director at Community Health Network, a health system based in Indianapolis, told Pharmacy Practice News. “You have to make sure providers agree with the titration parameters you’ve chosen, then make sure pharmacy is familiar with the policy, so when

COVID-19 pandemic, Dr. White said. “We have more nurses float between hospitals in the community to meet changing staffing needs during the pandemic, and titration parameters can be completely different from one hospital to the next,” she noted. “Building everything into the EHR as clearly and concisely as possible has made it so that it doesn’t matter whether it’s your first day on the job; you have clear instructions for what to do with that drug.” Dr. White cited another challenge she has faced when implementing these measures: the sense among employees that Joint Commission standards are “an annoyance.” To combat this, she routinely ties standards implementation to “our shared goal of patient safety,” she said. “Every single Joint Commission standard addresses a safety necessity and focuses on how to prevent errors, particularly in scenarios such as administration of complex orders and high-risk medications where an error can cause significant patient harm,” she said. The sources reported no relevant financial disclosures.

Kit Check’s Bluesight for Controlled Substances is Named Best in KLAS for 3rd Consecutive Year ©

Bluesight for Controlled Substances continues to be the most considered and selected diversion monitoring solution based on KLAS Research’s 2021 Drug Diversion Monitoring Report. Hospitals of all sizes continually recognize the solution for the ease of implementation, breadth of training resources, and comprehensive product support. See why over 250 hospitals have chosen Bluesight for Controlled Substances to keep both their staff and patients safe.

250+

Hospital Partners

50 Million+

Medication loops automatically reviewed

100% Audit

Every controlled substance dose from the wholesaler to the patient Flagged potential diversions

Learn more at KitCheck.com 786.548.2432 | info@kitcheck.com

137 days sooner

than 1st generation solutions

6 Operations & Management

Pharmacy Practice News • March 2022

ASHP News

ASHP Receives Federal Funds to Address Burnout By Dave Doolittle

SHP has been awarded more than $2 million to develop an educational program designed to help reduce burnout throughout the pharmacy profession and in healthcare overall. The grant, totaling $2.3 million over three years, was provided by the Department of Health and Human Services (HHS) through the Health Resources and Services Administration (HRSA). ASHP will use the grant to develop an educational curriculum that will allow healthcare workers, particularly those in the pharmacy profession, to implement local solutions to promote well-being and resilience, said Anna Legreid Dopp, PharmD, ASHP’s senior director of Clinical Guidelines and Quality Improvement. The curriculum will be another key ASHP resource aimed at reducing burnout among pharmacists, pharmacy residents and students, she said. “We know more needs to be done, and that’s why we’re so excited because this grant will allow us to do more to support the pharmacy workforce and those they work for in their practices,” Dr. Legreid Dopp said. ASHP for decades has recognized burnout as a patient care problem and has focused on helping members build resilience and develop tools to help address burnout, Dr. Legreid Dopp said. The problem is nationwide and complex, with at least 53% of health-system

pharmacists reporting some form of emotional exhaustion, depersonalization or a low sense of accomplishment, according to a 2018 survey (Am J Health Syst Pharm 2018;75[23 Supplement 4]:S93-S100). “Going back to the 1980s, our members have talked about the risk of burnout for those practicing in hospitals, but we have heard from members in the past 10 years that something is different in the environment,” Dr. Legreid Dopp said. “That caused our leadership to make a meaningful commitment to acknowledge there are inherent risk factors … that are causing those in the pharmacy workforce and healthcare workforce overall to burn out at a higher rate

than had been [the case] previously.” Those factors include the documentation demands of electronic health records, regulatory burdens, a feeling of diminishing autonomy and lack of time to recover from stressful events, Dr. Legreid Dopp said. The unprecedented demands of the COVID-19 pandemic have exacerbated the problem, she said. “At its core we see burnout as a patient care problem. If your clinician is experiencing burnout, then patient care might be at risk,” Dr. Legreid Dopp said. “We’re all about caring for the patient while recognizing that the pharmacy workforce is a critical part of the interprofessional healthcare team. Siloed approaches on this are short-sighted so we need to look

at this across all disciplines and to support the entire healthcare workforce.” ASHP resources to curb burnout include a dedicated continuing education program for members and a certificate program for healthcare organizations that focuses largely on how to create cultures of well-being and resilience. “Burnout is a local problem, and it requires local solutions,” Dr. Legreid Dopp said. “This is a systems problem, so our efforts are aimed at supporting individuals to fix their workforce.” ASHP is among 34 organizations that received HRSA grants to develop training programs to help public safety professionals address burnout, suicide, mental health conditions and substance use disorders, the HRSA said. Ten other organizations received grants to help healthcare organizations establish, improve or expand such programs, according to HRSA. “If you look at the awards being granted as part of this package, it speaks to the complexity of the issue and recognizes that there’s not an easy solution or one solution that can be [applied] across all sectors,” Dr. Legreid Dopp said. “It’s going to take a multifactorial response to addressing the issue. We see it as a big puzzle, and we’re excited to be a piece in that puzzle.” The sources reported no relevant financial disclosures.

New Certification Tool Highlights Practice Excellence By David Wild

ospitals and health systems have a new tool for honing best practices: ASHP’s Centers of Excellence certification program. “This certification [allows] institutions to differentiate themselves from others through innovative, high-quality, safe and effective pharmacy services,” said Douglas Scheckelhoff, MS, ASHP’s senior vice president. “There has long been discussion within health-system pharmacy to create a nursing Magnet-like program that is specific to pharmacy,” and the certification program meets that need, he noted during the ASHP 2021 Midyear Clinical Meeting and Exhibition, held virtually. One key component of the Centers of Excellence certification program is its focus on integration, according to David Warner, PharmD, ASHP’s senior director of consulting and practice. “Making sure the pharmacy department has strong relationships with other disciplines and leaders within the organization, that their services are integrated throughout the organization and that pharmacists

are involved in team-based care ensures the medication expertise of pharmacists is used throughout the organization to maximize drug safety and efficacy,” Dr. Warner said at the ASHP meeting. Achieving certification will depend on several areas, including the use of standards for leadership, management and patient care services. Surveyors also will look at quality and performance improvement initiatives as well as education, training and research programs, among other components. Organizations pursuing certification also will need to demonstrate that they use the most rigorous processes to support safe medication use across the organization, Dr. Warner said. Surveyors will evaluate medication-use policy, formulary approval processes and medication safety best practices, including the use of information technology and automation. According to Mr. Scheckelhoff, pharmacies that achieve certification can showcase their Centers of Excellence designation to patients as they choose where they want to receive care, as well

as highlighting this certification to a range of other stakeholders. “Centers can promote this certification to their payors, much the same as is done by the nursing profession relative to Magnet status, and certification can lead to research opportunities for pharmacy practice,” he said.

Gearing Up for a Gap Analysis Stephen Eckel, PharmD, MHA, the director of pharmacy for innovation services at UNC Medical Center and an associate professor at UNC Eshelman School of Pharmacy, in Chapel Hill, N.C., said his organization is gearing up for a gap analysis as a first step in evaluating the process of pursuing this certification. “Hospital patients want to make sure they’re getting the best care, and one pillar of optimal care is safe and appropriate medication administration utilization,” Dr. Eckel told Pharmacy Practice News. “Having a designation that the Department of Pharmacy is a Center of Excellence ensures that the public knows they’re being treated at an organization [that] follows all best practices and processes.”

Dr. Eckel cited another certification benefit: it can help pharmacy make the case for additional funding and use those funds to optimize pharmacy resources, as well as ensure operations and processes meet the most rigorous standards. “Every leader should want their pharmacy and their organization to perform at the highest level of patient care and safety,” Dr. Eckel said. More details regarding the certification can be found at bit.ly/3HF9MkC.

UC San Diego Scores First In mid-February, ASHP announced that the University of California San Diego Health is the first organization to be named a Certified Center of Excellence in Medication-Use Safety and Pharmacy Practice. The certification recognizes the health system’s “highperforming pharmacy department for its commitment to superior patient care,” ASHP noted in a press release. The sources reported no relevant financial disclosures.

Unit Dose Done Right Brightly Colored Labels Call Attention to Meds Requiring Special Handling

Unit Dos e Bar Cod , ing, Pharma c Nursing y & Supply Experts !

s Cold Seal s Tamper-Evident s Moisture Resistant s Ultraviolet Inhibitant s Reduces Cross Contamination s Ideal for Meds Covered by USP 800 s 6 and 12-month Beyond-Use Dating s 1-D and 2-D Bar Coding s Flexible Label and Report Formatting s Multiple Sizes and Shapes to Fit Your Meds & Storage Needs

Scan QR Code for more information and pricing.

Simple. Reliable.

800.523.8966

MediDose.com

8 Operations & Management

Pharmacy Practice News • March 2022

Specialty Pharmacy

‘OG’ Women of Specialty continued from page 1

pharmacies that continue to thrive both clinically and financially as a result of their efforts. But it wasn’t easy. JoAnn Stubbings, BSPharm, vividly recalls those early days of specialty pharmacy services at the University of Illinois at Chicago, where she directed specialty pharmacy for more than eight years and now serves as a clinical associate professor emerita at UIC College of Pharmacy. “It was about a decade ago, when there were really only a handful of hospitals dabbling in the specialty space. We were small,” she said. “I started with one part-time pharmacist and one prescription, and most of the other pharmacy leadership in the hospital were just like, ‘Why don’t you see what you can do with this?’ Meanwhile, the big pharmacies like CVS were going gangbusters into the specialty market.” What became known as “specialty” drugs had, in fact, long been the purview of hospitals and health systems. “Much of the prescription volume of the first specialty drugs originated out of the health systems. These were novel drug therapies used to manage complex, high-risk patients, such as transplant patients, cancer patients, people with multiple sclerosis and HIV and hemophilia,” said Rebekah Anguiano, PharmD, a clinical pharmacist and clinical assistant professor at UIC, whom Ms. Stubbings wooed from CVS Caremark in 2012, to help her establish UIC’s specialty pharmacy. However, hospitals and health systems were “asleep at the wheel” in the 1990s and early 2000s, Ms. Stubbings explained, as large traditional, mailorder pharmacies were building massive specialty businesses. “While specialty pharmacy was growing, hospitals were shutting down their external pharmacies because they didn’t see any profit in dispensing generic drugs,” she said. “But they weren’t paying attention to what was really going on as new original treatments came to market for diseases like hepatitis C [HCV], multiple sclerosis and Crohn’s disease.” Even then, these specialty drugs were very expensive—a concern for some health systems, which “weren’t excited to take that cost burden on at the time,” Dr. Anguiano said. “Also, these medications are complicated; they’re hard to get reimbursed; and many have cold chain shipping requirements, not to mention so many layers of medication management.” Another challenge: “In general, the prescription volume was low,” Dr. Anguiano said. “Unfortunately, this resulted in specialty prescriptions being channeled to outside big specialty

pharmacies, and health systems were initially shut out of the specialty niche.” Then a few early trailblazers, including Ms. Stubbings, Dr. Anguiano and a cadre of female leaders at other institutions saw the potential. “It made no sense not to adopt specialty in the health system,” said Ms. Stubbings, whose program had generated $60 million in annual revenue when she retired in 2020. “The patient is there, the doctors are there, the clinical trials are there. You’ve got everything packaged together beautifully, but you can’t dispense the drugs they need? That’s nonsensical.”

Above (left to right) is the specialty pharmacy team at Children’s Hospital of Colorado: Leslie Ruppe, PharmD, Emma Osbern, CPhT, Melody Odom, PharmD, John Tipton, CPhT, Taj Laugan, CPhT, Jenny French, PharmD, and Laura Rang, BSPharm, who launched the program.

Seeing the Future One of the first to call attention to the importance of specialty pharmacy for hospitals was Rita Shane, PharmD, the vice president and chief pharmacy officer at Cedars-Sinai Medical Center, in Los Angeles. In 2006, she convened a panel on specialty pharmacy at the ASHP Midyear Clinical Meeting. “It had become clear to me that the future of chronic disease management was going to include biologics, that specialty pharmacy would be really important and health-system pharmacy was very well positioned to provide those services,” she said. After the ASHP meeting, Dr. Shane published an article in the American Journal of Health-System Pharmacy (2007;64[22]:2382-2385) arguing that health-system pharmacy leaders should take ownership of specialty, including clinical guidelines, patient management, the revenue cycle and changing reimbursement models, and contracting. Dr. Shane met with the executive leadership at Cedars-Sinai and pointed out that the institution had a growing number of patients who required specialty services. “In addition to the obvious oncology population, we had a large rare disease population and many patients with inflammatory bowel disease,” she said. “While some early adopters understood the need—solid-organ transplant [clinicians], in particular, really recognized early the quality we brought to the table—it was a challenge early on to convey why we were investing in this. Our specialty pharmacy finally opened in 2014, and although there was initial concern about the costs of building the program, the value of the program to our patients and its focus on quality and safety became evident.” Some health systems partnered with larger outside specialty pharmacies, such as Shields or Diplomat, to build their services, but Cedars-Sinai did not. “We used Diplomat for our on-call service at one point, but other than that we insourced everything and built it all

‘It made no sense not to adopt specialty in the health system. The patient is there, the doctors are there, the clinical trials are there. You’ve got everything packaged together beautifully, but you can’t dispense the drugs they need? That’s nonsensical.’ —JoAnn Stubbings, BSPharm ourselves. In health systems, we have clinical pharmacists who have access to the electronic health record [EHR] along with the knowledge, skills and expertise to do comprehensive medication management,” Dr. Shane said. “In other settings, they may have accredited specialty pharmacists, but they don’t necessarily have our level of clinical expertise along with access to the [EHR] to determine that, for example, a drug that was started won’t be effective based on new biomarker data.”

Origin Stories Debbie Duckworth, PharmD, the senior director of specialty pharmacy and infusion services at the University of Kentucky, is another pioneer of health-system specialty pharmacy. Dr. Duckworth had spent more than two decades as the owner of her own pharmacy, the Medicine Shoppe, in Harrodsburg. “I partnered with the only other female pharmacist in the county at the time. We were both young mothers working predominantly for men, and we figured we could do this together, and it would give us some flexibility and allow us to attend to the needs of our families.” After she and her colleague decided to sell the business in 2010, Dr. Duckworth took on the position of helping to expand the University of Kentucky’s new retail pharmacy footprint. “We tasked a pharmacy fellow with the job of exploring and understanding whether or not UK should develop our own specialty pharmacy,” she said. “He came back and said

yes, so he became the first director of specialty pharmacy.” However, after the first six months, the new specialty pharmacy team was on the verge of collapse. “They were coming to my office in tears, saying if something didn’t change, they’d quit,” Dr. Duckworth said. “We pulled our data and realized that this team had exceeded our five-year business model for specialty in less than six months. We hadn’t had time to build the necessary infrastructure underneath them. No wonder they were ready to quit. Because I had had experience in owning my own store and having gone through accreditation processes, leaders felt it made sense for me to take over specialty pharmacy, which I did in March of 2015.” The specialty pharmacy team moved into a 5,000-square-foot space in UK’s Albert B. Chandler Hospital building—“which Some of the first specialty pharmacy medications were used to treat cancer, hepatitis C, HIV, multiple sclerosis and hemophilia, many of which required cold chain shipping.

Operations & Management

Pharmacy Practice News • March 2022

‘I ended up hiring 10 pharmacists and 30 pharmacy technicians, and all we did was prior authorizations, coordination of benefits and manufacturer programs—all the behind-the-scenes work to ensure that these prescriptions got filled and delivered.’ —Laura Rang, PharmD

sounded like a huge space at the time,” Dr. Duckworth said. “By August 2015, we were 20 team members strong and passed URAC accreditation with flying colors.” Today, Kentucky’s specialty pharmacy occupies 30,000 square feet in South Lexington, about 15 minutes from the main campus. In addition, the pharmacy’s contribution to the hospital’s revenue budget grew from about $17 million in 2016 to $53 million in 2021, Dr. Duckworth said.

‘I Don’t Really Know What That Means’ Kimberly Harrison, PharmD, received her pharmacy education at one of the other early health systems to establish a beachhead in specialty pharmacy, the University of Wisconsin-Madison, where she also completed what was then a brand-new two-year residency in medication systems and operations. “It was focused on developing pharmacy managers and keeping that expertise in the operations area,” Dr. Harrison said. After completing that program in 2012, she relocated to the University of Washington, in Seattle. “They were looking for a pharmacist who could devote time to projects as they came up across the health system,” she recalled. “I focused on two things: one was standardizing the 340B [Drug Pricing] program and the other was specialty pharmacy. When they told me they were interested in specialty pharmacy, I said, ‘I don’t really know what that means, so I’ll do some research.’” After consulting with specialty pharmacists at her alma mater for guidance, Dr. Harrison started building UW’s

specialty pharmacy by developing a small call center staffed by two pharmacy technicians supporting prior authorizations (PAs). “We were originally focused on the GI [gastroenterology] clinic, trying to give those patients options for fulfilling their prescriptions with us.” That was in 2014, when the FDA approved the first direct-acting antiviral therapy for HCV—a combination of simeprevir (Olysio, Janssen) and sofosbuvir (Sovaldi, Gilead)—revolutionizing treatment of that disease. “We then expanded our specialty pharmacy efforts into our hepatology clinic, and split one pharmacist between those two,” Dr. Harrison said. “The providers encouraged their patients to fill their prescriptions, showing them the benefits.” The revenue from gastrointestinal and HCV medications “justified us getting a third technician,” she added. “We worked with the Epic [EHR] team to build tools for pharmacists in the specialty clinics to document their work and enable us to get access to medications.” By the time the program expanded to include rheumatology, specialty pharmacy had taken over most of Dr. Harrison’s time. “I focused on getting feedback from patients as well,” she said. “If they had experience at other specialty pharmacies, what did they like or dislike? Our techs also took extra time with each patient to help figure out what we could do differently. For example, we learned early on that they wanted mail order and the ability to receive cold-chain medications at home, so we added that capability.” In 2015, with enough revenue to justify bringing on a full-time specialty pharmacy manager, Dr. Harrison hired Michael Alwan, PharmD. When he was promoted to a director of pharmacy position a year later, Dr. Harrison recruited Erica Diamantides, PharmD, who still manages the program today.

HIV a Trigger for Specialty Care Like Dr. Anguiano, Laura Rang, PharmD, got her start in specialty at CVS. “I went to pharmacy school during the HIV/AIDS pandemic; when I first graduated, that was one of my first experiences with specialty. There was such a stigma associated with those medications that we created a special pharmacy at CVS just for people with HIV,” she recalled. “I spent several years serving HIV patients who were marginalized and discriminated against, and who needed complex, expensive medications and would die without them. It turned out that other

disease states like hepatitis C, oncology, multiple sclerosis and rheumatoid arthritis needed specialty pharmacy, too. So I ran specialty pharmacy for CVS for about seven years, between 2007 and 2015, and learned all about it.” In 2015, Dr. Rang was recruited to help launch the new health-system specialty pharmacy at the University of Colorado Health, with headquarters in Aurora. “They had started filling those hepatitis C prescriptions and were making money by accident,” she said. “They realized that they needed their own specialty pharmacy.” Dr. Rang’s role was to create UCHealth’s specialty pharmacy medication access and renewal center—essentially, its PA program. “I ended up hiring 10 pharmacists and 30 pharmacy technicians, and all we did was prior authorizations, coordination of benefits and manufacturer programs—all the behindthe-scenes work to ensure that these prescriptions got filled and delivered.” In June 2019, she moved to Children’s Hospital of Colorado, where she launched that hospital’s specialty pharmacy. “This one, I got to plan and build from the beginning,” she said. “We now have a brick-and-mortar pharmacy and four clinical pharmacists with subspecialty PGY-2 pediatric training. These are very hard to find, and we’ve recruited from all over the country and are still recruiting more. We also have three operational pharmacists, three technicians and two interns/students.”

Building a Network This informal cadre of health-system specialty pharmacy pioneers came together in a more organized way around 2014, under the auspices of the University Healthcare Consortium, when then–associate vice president for specialty pharmacy Kevin Colgan, RPh, reached out to leading specialty consultant Suzette DiMascio, CHE, CMCE, CPC, the founder of CSI Specialty Group. “He told me that a lot of health systems wanted to figure out specialty, and wanted me to help develop strategies,” Ms. DiMascio said. “At that time, many CEOs and CFOs [chief financial officers] still wanted nothing to do with specialty pharmacy, because all they saw were expensive drugs and pictured it as a cost center, not a revenue center. But the leaders at the consortium got the vision; they saw the difference it could make when a hospital could care for a patient all the way through their discharge to home.” Ms. DiMascio met with Ms. Stubbings,

Specialty Pharmacy Dr. Harrison, Dr. Rang and others. “Hospitals and health systems have traditionally been very male-oriented, and the largely female early champions of hospital specialty pharmacies were getting nowhere with the C-suite,” Ms. DiMascio said. “But gradually we started to see a change in receptivity around 2016 or 2017. We had to show them the numbers for how they could use 340B funds to successfully implement a specialty pharmacy. Leaders like JoAnn and Kim were at the forefront of showing them that there was money on the table that they were missing out on—money they could use to fund the specialty pharmacy and help patients get better care. They had meds-to-beds programs for [high] cholesterol and diabetes and so on, but not for the most critically ill patients. Why not?” At many institutions, the real breakthrough came when the specialty pharmacy was able to demonstrate its ability to manage PAs. “That was, and continues to be, such a big burden on specialty clinics,” Dr. Anguiano said. “When we could off-load a portion of that burden and absorb it into the services we provide, with technicians and pharmacists who have specialized training in turning PAs around quickly with minimal involvement needed by the clinic, that was a huge win across the institution.” Managing access to limited distribution medications also helped the early health-system pioneers prove their worth. “It wasn’t just a revenue opportunity, but also a true patient care opportunity—to improve access, get patients started on treatment earlier, and provide better management on an ongoing basis,” Dr. Anguiano said. Throughout those early years, hundreds of phone calls fired back and forth between Illinois, Iowa, Washington, Kentucky and Wisconsin. “This was before everyone broke into getting accredited, and we were all just trying to figure it out,” Dr. Anguiano said. “JoAnn and I would be on the phone with Debbie or Kim and Laura. ‘How are you handling cold-chain shipping? How are you managing your call center?’ There was a lot of collaboration, and there still is.” This collaborative approach “is one of the things that sets our model apart from traditional specialty pharmacy,” Dr. Anguiano said. “We’re not in competition with each other; we have different patient populations that are really never going to overlap. If someone has a problem they’re trying to solve, they reach out to their colleagues across the nation, formulate a solution and then share it with others. It’s a great model, and has helped to improve processes and set standards and best practices.” The sources reported no relevant financial disclosures.

For patients with cGVHD æÐÌ ɖǠǡ řÐīĮ åĴÐī åðăķīÐ ďå Ĵ ăÐĮĴ ǡ Ĩīðďī ăðĊÐĮ ďå ĮřĮĴÐĉðÆ ĴìÐīĨřș ìÐăĨ ĴìÐĉǠȭǢ

ROCK ON

INDICATION REZUROCK™ (belumosudil) is indicated for the treatment of adult and pediatric patients 12 years and older with chronic graft-versus-host disease (chronic GVHD) after failure of at least two prior lines of systemic therapy.

IMPORTANT SAFETY INFORMATION Warnings and Precautions • Embryo-Fetal Toxicity: ĮÐÌ ďĊ ť ĊÌðĊæĮ ðĊ ĊðĉăĮ ĊÌ ðĴĮ ĉÐÆìĊðĮĉ ďå ÆĴðďĊș t'¢ tZ N ÆĊ ÆķĮÐ åÐĴă ìīĉ œìÐĊ administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with REZUROCK and for at least one week after the last dose Adverse Reactions • }ìÐ ĉďĮĴ ÆďĉĉďĊ ȧɖ ǡǟɦȨ ÌŒÐīĮÐ īÐÆĴðďĊĮș ðĊÆăķÌðĊæ ăÅďīĴďīř ÅĊďīĉăðĴðÐĮș œÐīÐ ðĊåÐÆĴðďĊĮș ĮĴìÐĊðș ĊķĮÐș ÌðīīìÐș ÌřĮĨĊÐș Æďķæìș ÐÌÐĉș ìÐĉďīīìæÐș ÅÌďĉðĊă ĨðĊș ĉķĮÆķăďĮāÐăÐĴă ĨðĊș ìÐÌÆìÐș ĨìďĮĨìĴÐ ÌÐÆīÐĮÐÌș æĉĉ æăķĴĉřă ĴīĊĮåÐīĮÐ ðĊÆīÐĮÐÌș ăřĉĨìďÆřĴÐĮ ÌÐÆīÐĮÐÌș ĊÌ ìřĨÐīĴÐĊĮðďĊ • qÐīĉĊÐĊĴ ÌðĮÆďĊĴðĊķĴðďĊ ďå t'¢ tZ N ÌķÐ Ĵď ÌŒÐīĮÐ īÐÆĴðďĊĮ ďÆÆķīīÐÌ ðĊ Ǡǧɦ ďå ĨĴðÐĊĴĮȘ }ìÐ ÌŒÐīĮÐ īÐÆĴðďĊĮ œìðÆì īÐĮķăĴÐÌ ðĊ ĨÐīĉĊÐĊĴ ÌðĮÆďĊĴðĊķĴðďĊ ďå t'¢ tZ N ðĊ ɔ Ǣɦ ďå ĨĴðÐĊĴĮ ðĊÆăķÌÐÌ ĊķĮÐ ȧǣɦȨȘ ÌŒÐīĮÐ īÐÆĴðďĊĮ ăÐÌðĊæ Ĵď ÌďĮÐ ðĊĴÐīīķĨĴðďĊ ďÆÆķīīÐÌ ðĊ ǡǨɦ ďå ĨĴðÐĊĴĮȘ }ìÐ ÌŒÐīĮÐ īÐÆĴðďĊĮ ăÐÌðĊæ Ĵď ÌďĮÐ ðĊĴÐīīķĨĴðďĊ ðĊ ɖ ǡɦ œÐīÐ ðĊåÐÆĴðďĊĮ ȧǠǠɦȨș ÌðīīìÐ ȧǣɦȨș ĊÌ ĮĴìÐĊðș ÌřĮĨĊÐș ìÐĉďīīìæÐș ìřĨďĴÐĊĮðďĊș ăðŒÐī åķĊÆĴðďĊ ĴÐĮĴ ÅĊďīĉăș ĊķĮÐș ĨřīÐŘðș ÐÌÐĉș ĊÌ īÐĊă åðăķīÐ œðĴì ȧǡɦ ÐÆìȨ • TďĊðĴďī ĴďĴă ÅðăðīķÅðĊș ĮĨīĴĴÐ ĉðĊďĴīĊĮåÐīĮÐ ȧ w}Ȩș ĊÌ ăĊðĊÐ ĉðĊďĴīĊĮåÐīĮÐ ȧ O}Ȩ Ĵ ăÐĮĴ ĉďĊĴìăř Drug Interactions • Strong CYP3A Inducers: Coadministration of REZUROCK with strong CYP3A inducers decreases belumosudil ÐŘĨďĮķīÐș œìðÆì ĉř īÐÌķÆÐ ĴìÐ ÐŨ ÆÆř ďå t'¢ tZ NȘ AĊÆīÐĮÐ ĴìÐ ÌďĮæÐ ďå t'¢ tZ N Ĵď ǡǟǟ ĉæ ĴœðÆÐ Ìðăř when coadministered with strong CYP3A inducers • Proton Pump Inhibitors: Coadministration of REZUROCK with proton pump inhibitors decreases belumosudil ÐŘĨďĮķīÐș œìðÆì ĉř īÐÌķÆÐ ĴìÐ ÐŨ ÆÆř ďå t'¢ tZ NȘ AĊÆīÐĮÐ ĴìÐ ÌďĮæÐ ďå t'¢ tZ N Ĵď ǡǟǟ ĉæ ĴœðÆÐ Ìðăř when coadministered with proton pump inhibitors

ORRa

75% (95% CI, 63-85; P<.0001) 1,4

REZUROCK achieved clinically and statistically ĮðæĊðť ÆĊĴ ÐŨ ÆÆř with the 200-mg once-daily dose in a real-world demographic of patients with cGVHD.1

• ZĊÆÐȭÌðăř ďīă ĉÐÌðÆĴðďĊ ĴìĴ ĴīæÐĴĮ ÅďĴì ðĊŦ ĉĉĴðďĊ ĊÌ ť ÅīďĮðĮ Ĵìīďķæì ĮÐăÐÆĴðŒÐ tZ Nǡ ðĊìðÅðĴðďĊ1-3 • CR was observed in all organsș ðĊÆăķÌðĊæ ĴìďĮÐ œðĴì ť ÅīďĴðÆ ĉĊðåÐĮĴĴðďĊĮ

• There was no death or new systemic therapy initiation in 62% (95% CI, 46-74) of the responder population at 12 months1 • Clinically meaningful improvements in QOL, with CS and CNI dose reductions and discontinuations ÆìðÐŒÐÌ ðĊ ÅďĴì īÐĮĨďĊÌÐīĮ and nonresponders5 • Well tolerated1

ASSIST

™

Enroll your patients with cGVHD in Kadmon ASSIST so our ĮĨÐÆðăðĮĴĮ ÆĊ ť ĊÌ ĴìÐ ÅÐĮĴ Ĩīďæīĉ Ĵď ť Ĵ řďķī ĨĴðÐĊĴĮȸ ÆďŒÐīæÐȘ Kadmon ASSIST ðĮ ŒðăÅăÐ Monday through Friday, 8ŬƢ-8ƲƢ ET, Åř ÆăăðĊæ 1-844-KADMON1 (523-6661).

VISIT REZUROCKhcp.com TO LEARN MORE cGVHD, chronic graft-versus-host disease; CNI, calcineurin inhibitor; CR, complete response; CS, corticosteroid; FDA, US Food and Drug Administration; NIH, National Institutes of Health; ORR, overall response rate; PR, partial response; QOL, quality of life; ROCK2, rho-associated coiled-coil–containing protein kinase-2. Proportion of patients who achieved CR or PR according to the 2014 NIH cGVHD Consensus Criteria in the 200-mg once-daily arm.1

IMPORTANT SAFETY INFORMATION (cont) ĮÐ ðĊ wĨÐÆðť Æ qďĨķăĴðďĊĮ • Pregnancy: ĮÐÌ ďĊ ť ĊÌðĊæĮ åīďĉ Ċðĉă ĮĴķÌðÐĮ ĊÌ ĴìÐ ĉÐÆìĊðĮĉ ďå ÆĴðďĊș t'¢ tZ N ÆĊ ÆķĮÐ åÐĴă ìīĉ œìÐĊ administered to pregnant women. There are no available human data on REZUROCK use in pregnant women to evaluate for a drug-associated risk. Advise pregnant women and females of reproductive potential of the potential risk to the fetus • Lactation: There are no data available on the presence of belumosudil or its metabolites in human milk or the effects on ĴìÐ ÅīÐĮĴåÐÌ ÆìðăÌș ďī ĉðăā ĨīďÌķÆĴðďĊȘ ÐÆķĮÐ ďå ĴìÐ ĨďĴÐĊĴðă åďī ĮÐīðďķĮ ÌŒÐīĮÐ īÐÆĴðďĊĮ åīďĉ ÅÐăķĉďĮķÌðă ðĊ ĴìÐ ÅīÐĮĴåÐÌ ÆìðăÌș ÌŒðĮÐ ăÆĴĴðĊæ œďĉÐĊ ĊďĴ Ĵď ÅīÐĮĴåÐÐÌ ÌķīðĊæ ĴīÐĴĉÐĊĴ œðĴì t'¢ tZ N ĊÌ åďī Ĵ ăÐĮĴ ďĊÐ œÐÐā after the last dose • Pediatric Use: The safety and effectiveness of REZUROCK have been established in pediatric patients 12 years and older. The safety and effectiveness of REZUROCK in pediatric patients less than 12 years old have not been established • Geriatric Use: Zå ĴìÐ Ǡǧǥ ĨĴðÐĊĴĮ œðĴì ÆìīďĊðÆ : ># ðĊ ÆăðĊðÆă ĮĴķÌðÐĮ ďå t'¢ tZ Nș ǡǥɦ œÐīÐ ǥǤ řÐīĮ ĊÌ ďăÌÐīȘ Uď clinically meaningful differences in safety or effectiveness of REZUROCK were observed in comparison to younger patients • Renal and Hepatic Impairment: Treatment with REZUROCK has not been studied in patients with pre-existing severe īÐĊă ďī ìÐĨĴðÆ ðĉĨðīĉÐĊĴȘ 9ďī ĨĴðÐĊĴĮ œðĴì ĨīÐȭÐŘðĮĴðĊæ ĮÐŒÐīÐ īÐĊă ďī ìÐĨĴðÆ ðĉĨðīĉÐĊĴș ÆďĊĮðÌÐī ĴìÐ īðĮāĮ ĊÌ ĨďĴÐĊĴðă ÅÐĊÐť ĴĮ ÅÐåďīÐ ðĊðĴðĴðĊæ ĴīÐĴĉÐĊĴ œðĴì t'¢ tZ N You are encouraged to report side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call Ǡȭǧǟǟȭ9# ȭǠǟǧǧȘ ďķ ĉř ăĮď ÆďĊĴÆĴ NÌĉďĊ qìīĉÆÐķĴðÆăĮș OO ș Ĵ ǠȭǧǦǦȭǢǦǦȭǦǧǥǡ Ĵď īÐĨďīĴ ĮðÌÐ ÐååÐÆĴĮȘ References: 1. REZUROCK. Package insert. Kadmon Pharmaceuticals, LLC; 2021. 2. Zanin-Zhorov A, Weiss JM, Nyuydzefe MS, et al. Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-dependent mechanism. Proc Natl Acad Sci USA. 2014;111(47):16814-16819. doi:10.1073/pnas.1414189111 3. Flynn R, Paz K, Du J, et al. Targeted rho associated kinase 2 inhibition suppresses murine and human chronic GVHD through a Stat3-dependent mechanism. Blood. 2016;127(17):2144-2154. doi:10.1182/blood-2015-10-678706 4. #Ĵ ďĊ ť ăÐȘ NÌĉďĊ qìīĉÆÐķĴðÆăĮș OO ț ǡǟǡǠȘ 5. Cutler CS, Lee SJ, Arai S, et al. Belumosudil for chronic graft-versus-host disease (cGVHD) after 2 or more prior lines of therapy: the ROCKstar study. Blood. 2021;blood.2021012021. doi:10.1182/blood.2021012021

Please see Brief Summary of full Prescribing Information on adjacent pages.

REZUROCK™ (belumosudil) tablets, for oral use Initial U.S. Approval: 2021 BRIEF SUMMARY: Please see package insert for full prescribing information. 1 INDICATIONS AND USAGE REZUROCK is indicated for the treatment of adult and pediatric patients 12 years and older with chronic graft-versushost disease (chronic GVHD) after failure of at least two prior lines of systemic therapy. 4 CONTRAINDICATIONS None. 5 WARNINGS AND PRECAUTIONS 5.1 Embryo-Fetal Toxicity Based on findings in animals and its mechanism of action, REZUROCK can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of belumosudil to pregnant rats and rabbits during the period organogenesis caused adverse developmental outcomes including embryo-fetal mortality and malformations at maternal exposures (AUC) less than those in patients at the recommended dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with REZUROCK and for at least one week after the last dose [see Use in Specific Populations (8.1, 8.3), Nonclinical Toxicology (13.1) in the full prescribing information]. 6 ADVERSE REACTIONS 6.1 Clinical Trial Experience Because clinical trials are conducted under widely variable conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared with rates of clinical trials of another drug and may not reflect the rates observed in practice. Chronic Graft versus Host Disease In two clinical trials (Study KD025-213 and Study KD025-208), 83 adult patients with chronic GVHD were treated with REZUROCK 200 mg once daily [see Clinical Studies (14.1) in the full prescribing information]. The median duration of treatment was 9.2 months (range 0.5 to 44.7 months). Fatal adverse reaction was reported in one patient with severe nausea, vomiting, diarrhea and multi-organ failure. Permanent discontinuation of REZUROCK due to adverse reactions occurred in 18% of patients. The adverse reactions which resulted in permanent discontinuation of REZUROCK in > 3% of patients included nausea (4%). Adverse reactions leading to dose interruption occurred in 29% of patients. The adverse reactions leading to dose interruption in ≥ 2% were infections (11%), diarrhea (4%), and asthenia, dyspnea, hemorrhage, hypotension, liver function test abnormal, nausea, pyrexia, edema, and renal failure with (2% each). The most common (≥ 20%) adverse reactions, including laboratory abnormalities, were infections, asthenia, nausea, diarrhea, dyspnea, cough, edema, hemorrhage, abdominal pain, musculoskeletal pain, headache, phosphate decreased, gamma glutamyl transferase increased, lymphocytes decreased, and hypertension. Table 2 summarizes the nonlaboratory adverse reactions. Table 2: Nonlaboratory Adverse Reactions in ≥ 10% Patients with Chronic GVHD Treated with REZUROCK REZUROCK 200 mg once daily (N=83) Adverse Reaction

Table 3 summarizes the laboratory abnormalities in REZUROCK. Table 3: Selected Laboratory Abnormalities in Patients with Chronic GVHD Treated with REZUROCK REZUROCK 200 mg once daily

Parameter

Grade 0-1 Baseline

Grade 2-4 Max Post

Grade 3-4 Max Post

(N)

(%)

Chemistry Phosphate Decreased

Gamma Glutamyl Transferase Increased

Calcium Decreased

Alkaline Phosphatase Increased

Potassium Increased

Alanine Aminotransferase Increased

Creatinine Increased

Lymphocytes Decreased

Hemoglobin Decreased

Platelets Decreased

Neutrophil Count Decreased

Hematology

7 DRUG INTERACTIONS 7.1 Effect of Other Drugs on REZUROCK Strong CYP3A Inducers Coadministration of REZUROCK with strong CYP3A inducers decreases belumosudil exposure [see Clinical Pharmacology (12.3) in the full prescribing information], which may reduce the efficacy of REZUROCK. Increase the dosage of REZUROCK when coadministered with strong CYP3A inducers [see Dosage and Administration (2.3) in the full prescribing information].

All Grades (%)

Grades 3-4 (%)

Infection (pathogen not speciﬁed)a

Viral infectionb

Bacterial infectionc

Astheniad

Edemae

Pyrexia Gastrointestinal

Nauseaf

Diarrhea

Abdominal paing

Dysphagia

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Based on findings from animal studies and the mechanism of action [see Clinical Pharmacology (12.1) in the full prescribing information], REZUROCK can cause fetal harm when administered to pregnant women. There are no available human data on REZUROCK use in pregnant women to evaluate for a drug-associated risk. In animal reproduction studies, administration of belumosudil to pregnant rats and rabbits during the period of organogenesis resulted in adverse developmental outcomes, including alterations to growth, embryo-fetal mortality, and embryo-fetal malformations at maternal exposures (AUC) approximately ≥ 3- (rat) and ≥ 0.07 (rabbit) times the human exposure (AUC) at the recommended dose (see Animal Data). Advise pregnant women and females of reproductive potential of the potential risk to the fetus.

Dyspneah

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Coughi

Nasal congestion

Hemorrhagej

Hypertension

Musculoskeletal paink

Muscle spasm

Arthralgia

Decreased appetite

Skin and subcutaneous Rashm

Pruritusn

Infections and infestations

General disorders and administration site conditions

Respiratory, thoracic and mediastinal

Vascular

Musculoskeletal and connective tissue

Nervous system Headachel Metabolism and nutrition

includes edema peripheral, generalized edema, face edema, localized edema, edema. includes nausea, vomiting. g includes abdominal pain, abdominal pain upper, abdominal pain lower. h includes dyspnea, dyspnea exertional, apnea, orthopnea, sleep apnea syndrome. i includes cough, productive cough. j includes contusion, hematoma, epistaxis, increased tendency to bruise, conjunctival hemorrhage, hematochezia, mouth hemorrhage, catheter site hemorrhage, hematuria, hemothorax, purpura. k includes pain in extremity, back pain, flank pain, limb discomfort, musculoskeletal chest pain, neck pain, musculoskeletal pain. l includes headache, migraine. m includes rash, rash maculo-papular, rash erythematous, rash generalized, dermatitis exfoliative. n includes pruritus, pruritus generalized. f

infection with an unspecified pathogen includes acute sinusitis, device related infection, ear infection, folliculitis, gastroenteritis, gastrointestinal infection, hordeolum, infectious colitis, lung infection, skin infection, tooth infection, urinary tract infection, wound infection, upper respiratory tract infection, pneumonia, conjunctivitis, sinusitis, respiratory tract infection, bronchitis, sepsis, septic shock. b includes influenza, rhinovirus infection, gastroenteritis viral, viral upper respiratory tract infection, bronchitis viral, Epstein-Barr viremia, Epstein-Barr virus infection, parainfluenzae virus infection, Varicella zoster virus infection, viral infection. c includes cellulitis, Helicobacter infection, Staphylococcal bacteremia, catheter site cellulitis, Clostridium difficile colitis, Escherichia urinary tract infection, gastroenteritis Escherichia coli, Pseudomonas infection, urinary tract infection bacterial. d includes fatigue, asthenia, malaise.

Proton Pump Inhibitors Coadministration of REZUROCK with proton pump inhibitors decreases belumosudil exposure [see Clinical Pharmacology (12.3) in the full prescribing information], which may reduce the efficacy of REZUROCK. Increase the dosage of REZUROCK when coadministered with proton pump inhibitors [see Dosage and Administration (2.3) in the full prescribing information].

Data Animal Data Embryo-fetal development studies were conducted in rats with administration of belumosudil to pregnant animals during the period of organogenesis at oral doses of 25, 50, 150, and 300 mg/kg/day in a pilot study and doses of 15, 50, and 150 mg/kg/day in a pivotal study. In the pilot study, maternal toxicity and embryofetal developmental effects were observed. Maternal toxicity (reduced body weight gain) occurred at 150 and 300 mg/kg/day doses. Increased post-implantation loss occurred at 50 and 300 mg/kg/day. Fetal-malformations were observed at ≥ 50 mg/kg/day and included absence of anus and tail, omphalocele, and dome shaped head. The exposure (AUC) at 50 mg/kg/day in rats is approximately 3 times the human exposure at the recommended dose of 200 mg. In an embryo-fetal developmental study in rabbits, pregnant animals administered oral doses of belumosudil at 50, 125, and 225 mg/kg/day during the period of organogenesis resulted in maternal toxicity and embryo-fetal developmental effects. Maternal toxicity (body weight loss and mortality) was observed at doses ≥ 125 mg/kg/day. Embryo-fetal effects were observed at doses ≥ 50 mg/kg/day and included spontaneous abortion, increased post-implantation loss, decreased percentage of live fetuses, malformations, and decreased fetal body weight. Malformations included those in the tail (short), ribs (branched, fused or deformed), sternebrae (fused), and neural arches (fused, misaligned, and deformed). The exposure (AUC) at 50 mg/kg/day in rabbits is approximately 0.07 times the human exposure at the recommended dose of 200 mg. 8.2 Lactation Risk Summary There are no data available on the presence of belumosudil or its metabolites in human milk or the effects on the breastfed child, or milk production. Because of the potential for serious adverse reactions from belumosudil in the breastfed child, advise lactating women not to breastfeed during treatment with REZUROCK and for at least one week after the last dose. 8.3 Females and Males of Reproductive Potential REZUROCK can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiating treatment with REZUROCK.

Contraception Females Advise females of reproductive potential to use effective contraception during treatment with REZUROCK and for at least one week after the last dose of REZUROCK. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be informed of the potential hazard to a fetus. Males Advise males with female partners of reproductive potential to use effective contraception during treatment with REZUROCK and for at least one week after the last dose of REZUROCK. Infertility Females Based on findings from rats, REZUROCK may impair female fertility. The effect on fertility is reversible [see Nonclinical Toxicology (13.1) in the full prescribing information]. Males Based on findings from rats and dogs, REZUROCK may impair male fertility. The effects on fertility are reversible [see Nonclinical Toxicology (13.1) in the full prescribing information]. 8.4 Pediatric Use The safety and effectiveness of REZUROCK have been established in pediatric patients 12 years and older. Use of REZUROCK in this age group is supported by evidence from adequate and well-controlled studies of REZUROCK in adults with additional population pharmacokinetic data demonstrating that age and body weight had no clinically meaningful effect on the pharmacokinetics of drug substance, that the exposure of drug substance is expected to be similar between adults and pediatric patients age 12 years and older, and that the course of disease is sufficiently similar in adult and pediatric patients to allow extrapolation of data in adults to pediatric patients. The safety and effectiveness of REZUROCK in pediatric patients less than 12 years old have not been established. 8.5 Geriatric Use Of the 186 patients with chronic GVHD in clinical studies of REZUROCK, 26% were 65 years and older. No clinically meaningful differences in safety or effectiveness of REZUROCK were observed in comparison to younger patients. Active ingredient made in India. Distributed and marketed by: Kadmon Pharmaceuticals, LLC Warrendale, PA 15086 1-877-377-7862 REZUROCK™ is a trademark of Kadmon Pharmaceuticals, LLC. © 2021 Kadmon Pharmaceuticals, LLC, Warrendale, PA 15086. All rights reserved. KAD25000266 10/21

14 Clnical

Pharmacy Practice News • March 2022

COVID-19 Pandemic

Many COVID-19 Trials Rife With Design Flaws By David Wild

ne problem that infectious disease physicians, pharmacists and other specialists had throughout the COVID-19 pandemic was accessing rigorous scientific data to guide clinical decision making. Such efforts were crucial to achieving at least some successful outcomes as case counts and mortality rates soared during the pandemic. To this end, many clinical trials were started. However, not all had that scientific rigor, and findings were often contradictory, making it difficult for healthcare providers and public health officials to advise patients and families. Early in the pandemic, COVID-19 treatment trials were hampered by enrollment of small study populations, use of surrogate markers and open-label design, according to researchers from the Johns Hopkins University School of Medicine. Since the beginning of the pandemic, more than 200 papers about COVID-19 have been retracted or withdrawn, and journals voiced concern about several others that have not been retracted, according to the website Retraction Watch. An early study by investigators at Johns Hopkins, perhaps, sheds light on why so many papers have been retracted. In 2020, the Hopkins investigators looked at some of the early studies that focused on treatment (BMJ Open 2020;10:e039978). (The retracted papers are not just about treatment, but touch on a wide number of COVID-19 topics.) The Hopkins study painted a picture of more than 200 disparate and disconnected trials carried out at dozens of sites around the world, leading to findings of limited clinical applicability.

Troubling Numbers 24% of studies were not randomized

29% were single-arm studies

Only 10% of the multi-arm studies were blinded

>1/3 of the trials used surrogate clinical end points or biomarkers Source: BMJ Open 2020;10:e039978.

other key websites that list clinical trials. The researchers found 201 clinical trials examining 92 drugs or convalescent plasma. Sixty-four trials studied monotherapy and 28 included a variety of treatment combinations. All but eight of the studies examined already-approved molecular entities. According to Dr. Mehta’s team, 75.7% (152/201) of the trials included randomization to treatment or a comparator. Thirty-six percent (55/152) of the trials had some form of blinding and 97 were open-label studies. Of the 24% (49/201) of studies that were not randomized, 29 were singlearm studies and 20 had one or two comparator arms, with only 10% of these multi-arm studies using a blinded design. When they looked at the geographic

‘You just need one or two trials to make a dramatic impact on the management of COVID-19, if they are well designed and find a treatment is useful.’ —Aaron E. Glatt, MD “We understand the urgency of clinical research on COVID-19, but this is a time when we need rigorous science to inform policy and clinical decision making,” lead researcher Hemalkumar Mehta, PhD, told Infectious Disease Special Edition, a sister publication to Pharmacy Practice News, shortly after publishing the report in June 2020. Dr. Mehta, an assistant professor in the Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health, in Baltimore, and colleagues scoured the World Health Organization’s clinical trials registry network as well as ClinicalTrials.gov, documenting studies registered up to March 26, 2020. They also searched major medical journals and

location of the trials, the researchers found that 49.8% (100/201) of the trials were registered in China, while 37.8% (78/201) were registered in the United States. More than half (110/201) of the studies were sponsored by hospitals or universities, 19.4% (39/201) were funded by governments, and the remainder were industry sponsored. Although 66.7% of the trials (134/201) included one or more clinical end points—such as COVID-19 symptoms, death, recovery, need for intensive care or hospital discharge—the remainder used surrogate end points or biomarkers, most commonly looking at viral load. Roughly 27% (54/201) of the studies aimed to enroll 50 or fewer patients,

‘Unfortunately, by generating a bunch of highly biased, heterogeneous and underpowered studies, [many COVID-19 study] results have been wildly contradictory.’ —C. Michael White, PharmD while 46.8% (94/201) had the goal of enrolling 100 or more patients. “Poor trial designs, lack of hard clinical end points and small trials may limit usefulness of data in guiding clinical practice,” said Dr. Mehta, noting the number of trials studying COVID-19 treatment increased since they conducted their analysis. As of early January 2022, there were more than 7,300 registered studies about COVID-19 with ClinicalTrials.gov, but not all were examining drugs or plasma. “Since our study, government and pharma sponsorship of these trials has also increased, which will make trials more collaborative, bigger and hopefully with better-designed elements,” he said.

A Pharmacist’s Take C. Michael White, PharmD, the head of the Department of Pharmacy Practice at the University of Connecticut School of Pharmacy, in Storrs, acknowledged that although the research and clinical community did not have the luxury to wait for conclusive studies during the early days of the pandemic, the community “could have done research so much better if we had a true pandemic response infrastructure in place. Instead, everyone did their own thing instead of running a logical cluster randomized trial, in which some sites would have looked at standard of care and others studied standard of

care plus a set number of different interventions,” explained Dr. White, who was not involved in the Hopkins study but is no stranger to medical research, having published more than 410 peer-reviewed publications during his pharmacy career. Using such a standard-of-care lens in COVID-19 research would have led to a balanced data set and more reliable but still rapid results, he said. “Unfortunately, by generating a bunch of highly biased, heterogeneous and underpowered studies, [many COVID-19 study] results have been wildly contradictory,” Dr. White stressed. Aaron E. Glatt, MD, the chair of the Department of Medicine at Mount Sinai South Nassau, in Oceanside, N.Y., had a different perspective. Although there are “a tremendous number of differences in the studies, the critical and heartening thing is that there are so many studies underway looking at so many different interventions, both old and new,” he said. Although some studies were not very helpful, “you just need one or two trials to make a dramatic impact on the management of COVID-19, if they are well designed and find a treatment is useful,” said Dr. Glatt, who was not involved in the research. The sources reported no relevant financial disclosures.

WITH A REVOLUTIONARY 10-MINUTE HAZARDOUS DRUG TESTING SYSTEM. At BD, healthcare worker safety is an utmost priority. The same is true of developing new technologies to help you quickly identify and address hazardous drug contamination. The BD ® HD Check system gives you a new breakthrough technology that lets you easily monitor and identify surface contamination in less than 10 minutes *, not the days or weeks that conventional testing technologies require. The result? A fast, new way to stay on top of contamination monitoring and adherence to your healthcare worker safety policies—for a difference your team will appreciate. Discover the confidence of test results in minutes, not weeks. Discover the new BD.

Identify surface contamination in LESS THAN 10 MINUTES* Now detecting cyclophosphamide, doxorubicin and methotrexate

Learn how to better protect your team at bd.com/bdhdcheck *For select hazardous drugs. BD and the BD Logo are trademarks of Becton, Dickinson and Company or its affiliates. © 2020 BD. All rights reserved. BD-5049 (1/20)

16 Focus on Oncology

Pharmacy Practice News • March 2022

CAR-T Therapy Insights continued from page 1

treatment choice in these challenging malignancies, experts noted.

CAR T-Cell Therapy Versus Standard of Care ZUMA-7

Of several studies presented on CAR T cells at the ASH meeting, two involved trials in relapsed or refractory (R/R) lymphoma. One, ZUMA-7, found axicabtagene ciloleucel (Yescarta, Kite) more effective than the current standard of care (SOC) for R/R large B-cell lymphoma. However, a much anticipated second trial, called BELINDA, failed to show an advantage for tisagenlecleucel (Kymriah, Novartis) over SOC in R/R aggressive non-Hodgkin lymphoma (aNHL).

advantage (HR, 0.398; P<0.0001) after two years of follow-up. The median EFS was 8.3 months in the CAR T-cell arm versus 2.0 months on SOC. The greater median overall survival (OS; HR, 0.730; P=0.027) for the CAR T-cell arm did not reach a predefined level of significance, but the objective response rate (ORR) did (83% vs. 50%; P<0.0001). These differences were observed despite the fact that 56% of the SOC arm eventually received off-protocol CAR T-cell therapy. Treatment-related deaths occurred in one patient in the CAR T-cell arm and two patients in the SOC arm. Grade 3 or higher cytokine release syndrome was observed in 6% of patients. The side effects of this CAR T-cell regimen were “manageable,” noted lead investigator Frederick Locke, MD, the vice chair of the Blood and Marrow Transplant and Cellular Immunotherapy Department, Moffitt Research Center, University of South Florida, Tampa. He indicated that the data support CAR T-cell therapy as a new SOC in R/R large B-cell lymphoma. BELINDA

Autologous CAR T-cell therapy must be stored in liquid nitrogen; off-the-shelf options have no such requirements. Source: David Caulfield, the Pharmaceutical Journal.

Not deterred by the results of the BELINDA trial, Laurie Sehn, MD, the chair of the Lymphoma Tumor Group, British Columbia Cancer Agency, in Vancouver, is convinced that the “remarkable” overall data with CAR T cells will exert an enormous impact on clinical practice. Indeed, she said it is “inevitable” that CAR T-cell therapy will become the SOC in advanced forms of lymphoma. In the multinational ZUMA-7 trial (abstract 2), 359 patients with R/R large B-cell lymphoma were randomized to a single infusion of axicabtagene ciloleucel or SOC. Axicabtagene ciloleucel was administered after completing the multistep process that involves conditioning of the patient’s own T cells, leukapheresis, T-cell engineering and reinfusion. SOC consisted of two to three cycles of investigator-selected but protocoldefined platinum-based chemotherapy (PCT) regimens. In the case of lack of response to SOC, crossover to CAR T cells was permitted. On the primary outcome of event-free survival (EFS), the hazard ratio (HR) translated into a more than 60% relative

In the phase 3 BELINDA trial (abstract LBA-6), 322 patients with R/R aNHL were randomized to a single infusion of tisagenlecleucel or an investigator choice of protocol-defined PCT regimens. The PCT was followed by hematopoietic cell transplant (HCT) in responders or a second best-choice regimen in nonresponders. Patients were eligible for the study if they failed to respond or relapsed within 12 months of first-line therapy. At three months, the median EFS, which was the primary end point, was exactly the same in the two study arms. The ORR was only slightly greater in the CAR T-cell arm (46% vs. 43%). In the study design, patients in the

CAR T-cell arm were permitted to receive an optional bridging treatment with one of the protocol-defined PCT regimens followed by lymphodepletion. This bridging led to an inherent delay in CAR T-cell delivery, according to principal investigator Michael R. Bishop, MD, the director of the Hematopoietic Stem Cell Transplantation Program at University of Chicago Medicine. He considers this one potential explanation for the negative result. Dr. Bishop stressed that the trial, although negative, offers important insights that “will inform use of cellular therapy in the second-line R/R aNHL setting [and] guide future CAR-T trials.”

Off-the-Shelf Treatments As noted, autologous CAR T-cell therapy can be subject to supply challenges, given the variability of patients’ T-cell yields. The agents also have special storage requirements. Thus, off-the-shelf allogeneic treatments that use conventional targeted chemotherapy approaches can be viable alternatives. Valemetostat tosylate is one such agent, and was associated with highly encouraging activity in a small but pivotal trial that enrolled patients with R/R adult T-cell leukemia/ lymphoma (ATL) (abstract 303). In a highly pretreated population, of which nearly all (96%) had received mogamulizumab-kpkc (Poteligeo, Kyowa Kirin), ORR was 48%, with 20% achieving a complete response to valemetostat. In addition to the high rates of activity, eight of the 25 patients are still deriving benefit and remain on therapy after a median of 28 weeks of followup, the investigators reported. The median duration of remission has not yet been reached in a population that had few treatment options, the investigators said. Grade 3 or greater treatment-related adverse events occurred in 15 (60%) of the 25 patients enrolled, but only two discontinued treatment due to adverse events. The most common adverse events

More Leukemia/Lymphoma News on the Web Managing Asparaginase Hypersensitivity Reactions

were thrombocytopenia, dysgeusia, anemia and alopecia, which was observed in 40% of patients, but these were manageable, according to to the researchers. As for the agent’s key mechanisms of action, valemetostat targets the enhancer of zeste homolog 1 and 2 (EZH1 and EZH2), which are implicated in the epigenetics of T-cell leukemia/lymphoma proliferation. Evidence that this is a clinically important and viable target of disease control was derived from a phase 1 trial (abstract S218) of patients with R/R NHLs, including peripheral T-cell lymphoma (PTCL), ATL and other cancers, presented at the European Hematology Association 2021 Virtual Congress. Despite the limited size of the current study, the data have been submitted to regulatory authorities in Japan. Further studies are planned, according to the researchers, including a pivotal phase 2 study known as VALENTINE-PTCL01. The trial will assess the safety and efficacy of valemetostat in patients with R/R PTCL and ATL (ClinicalTrials.gov Identifier: NCT04703192).

A Hematology/Oncology Pharmacist’s Take In treatment-experienced patients with advanced lymphoma, the top concern for many pharmacists is managing the adverse events, according to Aseala I. Abousaud, PharmD, a lymphoma clinical pharmacy specialist in the Winship Cancer Institute of Emory Healthcare, in Atlanta. Focusing on the expanding role of CAR T-cell therapy in R/R lymphoma, she urged pharmacists to stay current with risks as well as efficacy. “I do believe pharmacists will be playing a major role in CAR T-cell therapy, especially in the prevention and management of side effects,” Dr. Abousaud said. The proportion of cancer centers already offering this option has been growing steadily. Promising results with off-the-shelf products suggest that it might soon be possible to offer CAR T-cell therapy to a much larger population. On this basis, Dr. Abousaud recommended that pharmacists who are active in programs with substantial cases of R/R lymphoma need to understand the differences in the risks of the expanding number of CAR T-cell products as well as their relative ability to extend survival.

bit.ly/36aglhj Studies Point to Optimal Dosing in Acute Leukemia And Lymphoma bit.ly/34lMn9g Another Off-the-Shelf CAR-T Therapy Shows Promise bit.ly/3rGnj60

Dr. Abousaud reported no relevant financial disclosures. Dr. Bishop reported financial relationships with Arcellx, Autolus, Bristol Myers Squibb, Kite and Novartis. Dr. Locke reported financial relationships with GammaDelta, Iovance, Janssen, Kite, Novartis and Umoja. Dr. Sehn has financial relationships with AbbVie, Amgen, Apobiologix, AstraZeneca, Debiopharm, Genmab, Gilead, Incyte, Janssen, Karyopharm, Kite, Lundbeck, Merck, Morphosys, Novartis, Roche/Genentech, Sandoz, Seattle Genetics, Takeda, TG Therapeutics and Verastem.

Focus on Oncology 17

Pharmacy Practice News • March 2022

Tech helps risk-stratify pediatric leukemia patients

Is It Time for Next-Generation Cancer Sequencing? By Ted Bosworth

y accurately assessing minimal residual disease (MRD) status, next-generation sequencing (NGS) is showing promise for improving the risk stratification of pediatric patients with newly diagnosed acute lymphoblastic leukemia (ALL), according to a multicenter study (abstract 618) presented at the 2021 annual meeting of the American Society of Hematology (ASH).

“The majority of discrepant cases were just above the FCM limit of detection,” he said. In this series, NGS was used as the primary method of MRD-based risk determination. FCM was employed as a backup. Initial bone marrow evaluations were performed at the time of diagnosis and four weeks after induction therapy, identified as the first time point (TP1). Patients with a high MRD, identified as

‘This technology gives providers and pharmacists enhanced information to give more individualized care to these pediatric ALL patients.’ —Tara Higgins, PharmD Unlike current assays such as flow cytometry (FCM), NGS assays employ unique genetic sequences in leukemia cells “to detect MRD at the level of 12 leukemic cells in 1 million cells,” according to Jonathan D. Paolino, MD, a pediatric hematology/oncology fellow at Dana-Farber Cancer Institute, in Boston, and a study co-investigator. The multicenter study included 317 children being treated on the DanaFarber Cancer Institute ALL protocol. When compared with FCM, which was also performed, NGS identified a higher proportion of cases with high MRD status, Dr. Paolino reported.

equal to or greater than 1 leukemic cell per 10,000 cells (10-4), received intensified therapy and additional MRD assessments after 10 and 20 weeks of therapy. Patients from the age of 12 months through 21 years with B- or T-cell ALL were eligible for inclusion. Most (84%) had B-cell ALL and were less than 10 years of age (67%). When determined on the basis of age, baseline leukocyte count, central nervous system leukemia status, immunophenotype and disease biology, 52% were identified as low risk, 31% as high risk and 17% as very high risk. Among 70 B-ALL patients with high

MRD, 43% (n=30) were high by NGS (≥10-4) when FCM was low (<10-4; n=4) or undetectable (n=26), with 90% of discrepancies at the NGS level of 10-4. In contrast, among 28 T-ALL patients with high TP1 MRD, 75% (n=21) were high by NGS alone, all with undetectable FCM, according to the study. “Sixty-seven percent of these patients had NGS MRD at the level of 10-4 and the remaining 33% were in the range of 10-3 to less than 10-1,” Dr. Paolino reported. “NGS additionally detected MRD in the range of 10-6 to 10-4 for 160 patients who had undetectable disease on FCM at TP1.” The greater sensitivity of NGS for MRD is consistent with published studies, Dr. Paolino noted. Dr. Paolino said the prognostic relevance of low MRD levels is being evaluated “and awaits longer followup.” However, presuming that more sensitive assessment of MRD status at baseline or after induction therapy can guide the intensification of treatment to achieve better outcomes, the use of NGS “is feasible.”

Other NGS Efforts The multicenter study led by Dr. Paolino is not the only effort to establish NGS as a standard of care for risk stratification in pediatric patients, according to Tara Higgins, PharmD, a clinical specialist in pediatric hematology, oncology and bone marrow transplant at the University of

Florida Shands Children’s Hospital, in Gainesville. She said a multicenter study of NGS in the evaluation of pediatric ALL is also being run through the Children’s Oncology Group. “This multicenter trial and the DFCI study will hopefully be able to determine the best place in practice to utilize NGS as a standard of care,” she told Pharmacy Practice News. “This technology gives providers and pharmacists enhanced information to give more individualized care to these pediatric ALL patients.” Drs. Higgins and Paolino reported no relevant financial disclosures. Two co-investigators reported financial relationships with Adaptive Biotechnologies, Jazz Pharmaceuticals, Servier, Syndax and Takeda.

For more news on next-generation sequencing, see page 20.

BiTE Therapy Shows Promise in R/R ALL By Ted Bosworth

lthough only a phase 1b dose-finding study in patients with relapsed/ refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL), all but one patient treated with a subcutaneous formulation of the bispecific T-cell engager (BiTE) blinatumomab (Blincyto, Amgen) achieved a complete hematologic response, with no minimal residual disease (MRD), according to interim data presented at the 2021 annual meeting of the American Society of Hematology. “The study demonstrated encouraging anti-leukemia activity in a heavily pretreated population,” reported Pilar Martínez Sánchez, MD, PhD, a researcher in the Department of Hematology, Hospital Universitario 12 de Octubre, in Madrid. She called the

safety profile “manageable.” Blinatumomab has been available for the treatment of R/R B-cell precursor ALL in adults and children since 2014, but the approved formulation is administered intravenously. In this analysis, six patients received a lower first dose of subcutaneous blinatumomab for several days, followed by a higher subcutaneous dose multiple times weekly. The subcutaneous dose resulted in therapeutic exposures that were comparable to the IV formulation, “with mean average concentrations of 853 mg/mL,” Dr. Sánchez reported. Within two cycles of blinatumomab treatment, three patients had a complete hematologic response with no measurable MRD. A third patient had achieved a morphological partial response when

treatment was discontinued on day 15 of the first cycle after progression of extramedullary disease. Two patients are still on treatment. Both have also achieved a complete response with no MRD. These results are impressive in a patient population with advanced disease, Dr. Sánchez noted. The median bone marrow blast count was 85%, with only one patient having a blast count greater than 50%. The patients had received up to four prior lines of therapy, and two had relapsed after hematopoietic cell transplantation. The safety profile was similar to that reported for IV blinatumomab. There were no cases of grade 3 or higher cytokine release syndrome. The data have encouraged further development of an injectable blinatumomab formulation. “Subcutaneous delivery may improve the convenience and satisfaction of candidates for blinatumomab therapy,” said Dr. Sánchez, indicating that this could expand the routine use

of this option in advanced disease.

Taking a Bigger BiTE These data have the potential to substantially expand the use of this BiTE therapy in ALL and other diseases in which it is active, according to Anthony J. Perissinotti, PharmD, a clinical pharmacist specialist for the Inpatient Hematology Clinical Team at the University of Michigan, in Ann Arbor. “A major limitation to the widespread use of blinatumomab for R/R ALL or persistent MRD-positive disease is the logistical barrier of a continuous infusion over 28 days for multiple potential cycles,” Dr. Perissionitti said. “A strategy to reduce patient and healthcare resource burden such as subcutaneous administration would be a very welcomed approach clinically and especially for patients and their families.” The sources reported no relevant financial disclosures.

18 Focus on Oncology

Pharmacy Practice News • March 2022

Driving CAR T-Cell Rx continued from page 1

therapy, including patient preference, shorter hospital lengths of stay and freeing up hospital beds for other interventions, Dr. McGann told Pharmacy Practice News in advance of a presentation at the 2022 annual meeting of the Hematology/ Oncology Pharmacy Association. Clinicians also are honing their ability to manage adverse reactions to outpatient CAR T-cell therapy, she said.

In view of those benefits, MUSC was an early adopter of moving the treatments to the outpatient setting, Dr. McGann said. “While there are certain products that we always give on an inpatient basis, we often try to at least give the cells on an outpatient basis to help, as noted, with reimbursement. We may still admit the patients later that night, but at least they receive the cells as an outpatient.”

Indeed, 80% of patients at MUSC are administered the CAR T-cell infusion outside of the hospital, Dr. McGann noted.

Second-Line Therapy There is yet another driver for moving CAR T-cell treatments beyond the hospital: Several recent studies have indicated the potential benefit of the regimens in second-line therapy, which could dramatically increase the number of patients eligible to receive them. (For a list of the five approved CAR T-cell therapies, see box.) For example, the FDA is expected

to act by April 1, on Kite Pharma’s supplemental biologics license application for the use of axicabtagene ciloleucel (Yescarta) as a second-line therapy in relapsed or refractory large B-cell lymphoma (LBCL). In December 2021, findings presented at the American Society of Hematology Meeting & Exposition showed that axicabtagene ciloleucel quadrupled event-free survival (EFS) compared with the current standard of care, which includes high-dose therapy and autologous stem cell transplant (ASCT) (N Engl J Med 2022;386[7]:640-654). At

5 Approved CAR T-Cell Treatments 1. Tisagenleleucel (Kymriah, Novartis): relapsed/refractory (R/R) acute lymphocytic leukemia, (ALL), large B-cell lymphoma (LBCL) 2. Axicabtagene ciloleucel (Yescarta, Kite Pharma): R/R LBCL, follicular lymphoma

Free CE/CME now available!

3. Brexucabtagene autoleucel (Tecartus, Kite Pharma): R/R mantle cell lymphoma, R/R ALL

1.0 AMA PRA Category 1 Credit™ 1.0 ACPE credit

4. Lisocabtagene maraleucel (Breyanzi, Bristol Myers Squibb/Juno): R/R LBCL 5. Idecabtagene vicleucel (Abecma, Bristol Myers Squibb/Celgene): R/R multiple myeloma

Ensuring Optimal Management of Antibiotic-Resistant Hospital- and VentilatorAcquired Pneumonia RELEASE DATE: JUNE 8, 2021 EXPIRATION DATE: JUNE 30, 2022

CHAIR Keith S. Kaye, MD, MPH

Jointly provided by Postgraduate Institute for Medicine and Applied Clinical Education

Professor Infectious Diseases, Internal Medicine University of Michigan Taubman Center Ann Arbor, Michigan

FACULTY Andrew F. Shorr, MD, MPH, MBA

Supported by an independent educational grant from Shionogi Inc.

Head of Pulmonary and Critical Care Medicine MedStar Washington Hospital Center Professor of Medicine Georgetown University Washington, DC

David P. Nicolau, PharmD, FCCP, FIDSA Distributed by Infectious Disease Special Edition, Pharmacy Practice News, and cmezone.com

Director, Center for Anti-Infective Research and Development Hartford Hospital Hartford, Connecticut

the same meeting, an interim analysis from the TRANSFORM trial, comparing lisocabtagene maraleucel (Breyanzi, Bristol Myers Squibb/Juno) and standard of care, found the CAR T-cell therapy yielded a risk reduction of 65% in EFS in patients with LBCL in the second-line setting (Blood 2021;138[suppl 1]:91). Those clinical successes come with potentially serious adverse reactions, Dr. McGann stressed, including cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome. “But as toxicity management for these therapies has evolved, with early intervention and additional experience resulting in lower rates of acute high-grade toxicity, there have been more opportunities for initial outpatient administration and admission to the inpatient setting only when indicated.” Still, challenges remain, Dr. McGann stressed, including a “heavy reliance on the patient’s caregiver and daily visits to the treatment center, and you may need immediate inpatient bed availability.” Overall, “you do not have the same ease of close monitoring and interventions that you have with inpatients.” Creating a set of standard operating procedures can help clinicians navigate at least some of these challenges. Dr. McGann cited three key areas: institutional considerations, product considerations and patient considerations. Institutional Considerations

Regulatory requirements. The hospital and associated clinics must be

Access today at www.cmezone.com/CU211

Focus on Oncology 19

Pharmacy Practice News • March 2022

certified and enrolled in the Risk Evaluation and Mitigation Strategies (REMS) program, with all relevant staff completing REMS knowledge assessment. Training logs must be maintained, and the institution must comply with audits and report adverse events. Care coordination. A well-coordinated multidisciplinary team must include a medical director, attending physicians, advanced practice providers, nursing, pharmacy, social work, behavioral medicine, apheresis, cell-processing laboratory and information technology. The emer-

gency department, neuro-oncology, and ICU also must be part of this team. Appropriate outpatient support. This component includes an outpatient clinic/ infusion center that is open daily, ideally with telemedicine capability, and a CAR T-cell therapy team that is on-call 24/7. Communication and transitions of care. These key elements include clearly defined indications for admission, reserved bed availability, and a staff email or “oncology road map.” “It’s critical that you have support on the outpatient side for having the patient come in every single day, that the whole team is aware of these patients, and that the CAR T–specific on-call service is available at all times,” Dr. McGann said. Product Considerations

Clinicians should have a strong understanding of the differences in toxicities of each CAR T-cell therapy, Dr. McGann stressed. “For example, Yescarta and Tecartus [brexucabtagene autoleucel, Kite Pharma] have a CD28 costimulatory domain that amplifies early CAR T-cell expansion, which may lead to more toxicities such as CRS. With these agents, we typically lymphodeplete and infuse the cells in the outpatient setting, but then admit the patient in the evening because we anticipate they will develop a fever, which is the first sign of CRS.” Patient Factors

The patient’s own characteristics are key. “We need to look at things like disease burden. Are patients more at risk of

‘With [axicabtagene ciloleucel and brexucabtagene autoleucel], we typically lymphodeplete and infuse the cells in the outpatient setting, but then admit the patient in the evening because we anticipate they will develop a fever, which is the first sign of [cytokine release syndrome].’ —Mary McGann, PharmD having early-onset and high-grade CRS based on their disease status? What are their comorbidities that may put them at risk for having more severe toxicities? Other concerns include health literacy and compliance. Are patients able to come into the clinic every day? Are we confident that they can take their medications on time and that they can identify

early toxicities that may develop at home? Do they have a reliable caregiver who can be there 24/7 to help with the whole process? That’s a vital aspect to giving this therapy in the outpatient setting.”

What Do the Data Say? It’s also important to follow the data. Dr. McGann cited two recent

single-center studies that were reasonably successful in administering axicabtagene ciloleucel and tisagenleleucel (Kymriah, Novartis) in the outpatient setting. In a study from Mayo Clinic, presented at the 2021 annual meeting of the American Society for Clinical Oncology, 64 of 72 axicabtagene ciloleucel see CAR-T ROLLOUT, page 20

Innovations that deliver

SMOFlipid is the first and only lipid injectable emulsion for adults in the U.S. that delivers a unique blend of 4 oil sources: soybean oil (30%), medium-chain triglycerides (30%), olive oil (25%), and fish oil (15%). It’s just one of our innovations that nourish.

Discover the SMOF difference at:

www.FreseniusKabiNutrition.com/deliver SMOFlipid is indicated in adults as a source of calories and essential fatty acids for parenteral nutrition (PN) when oral or enteral nutrition is not possible, insufficient, or contraindicated. Limitations of Use: The omega-6: omega-3 fatty acid ratio and Medium Chain Triglycerides in SMOFlipid have not been shown to improve clinical outcomes compared to other intravenous lipid emulsions. Contraindications: Known hypersensitivity to fish, egg, soybean, or peanut protein, or to any of the active ingredients or excipients. Severe hyperlipidemia or severe disorders of lipid metabolism with serum triglycerides > 1,000 mg/dL.

WARNING: DEATH IN PRETERM INFANTS • Deaths in preterm infants after infusion of intravenous lipid emulsions have been reported in the medical literature. • Autopsy findings included intravascular fat accumulation in the lungs. • Preterm infants and low-birth-weight infants have poor clearance of intravenous lipid emulsion and increased free fatty acid plasma levels following lipid emulsion infusion.

Please see Brief Summary of Prescribing Information, including Boxed Warning, for SMOFlipid on the next page.

20 Focus on Oncology

Pharmacy Practice News • March 2022

Combating Resistance to Targeted Therapies By Gina Shaw

Next-generation sequencing (NGS) has been a useful tool for guiding first-line tyrosine kinase inhibitor (TKI) therapy in patients with non-small cell lung cancer (NSCLC) and other challenging malignancies. Now, clinicians hope that the test also may guide second-line use of these agents. Given how common it is for tumor cells to mutate and develop resistance to chemotherapy, having NGS on hand to

help choose alternative therapies in such cases would be an advantage, noted Chris Kapolas, PharmD, a clinical pharmacy

SMOFLIPID (lipid injectable emulsion), for intravenous use BRIEF SUMMARY OF PRESCRIBING INFORMATION This brief summary does not include all the information needed to use SMOFlipid safely and effectively. Please see full prescribing information, including Boxed Warning for SMOFlipid (lipid injectable emulsion), for intravenous use at www. FreseniusKabiNutrition.com.

INDICATIONS AND USAGE SMOFlipid is indicated in adults as a source of calories and essential fatty acids for parenteral nutrition (PN) when oral or enteral nutrition is not possible, insufficient, or contraindicated. Limitations of Use The omega-6: omega-3 fatty acid ratio and Medium Chain Triglycerides in SMOFlipid have not been shown to improve clinical outcomes compared to other intravenous lipid emulsions. DOSAGE AND ADMINISTRATION The recommended daily dosage in adults is 1 to 2 grams/kg per day and should not exceed 2.5 grams/kg per day. SMOFlipid 1000 mL is supplied as a Pharmacy Bulk Package for admixing only and is not for direct infusion. Prior to administration, transfer to a separate PN container. Protect the admixed PN solution from light. CONTRAINDICATIONS Known hypersensitivity to fish, egg, soybean, or peanut protein, or to any of the active ingredients or excipients. Severe hyperlipidemia or severe disorders of lipid metabolism with serum triglycerides > 1,000 mg/dL. WARNINGS AND PRECAUTIONS • Death in Preterm Infants: (see BLACK BOX WARNING) • Hypersensitivity Reactions: SMOFlipid contains soybean oil, fish oil, and egg phospholipids, which may cause hypersensitivity reactions. Cross reactions have been observed between soybean and peanut oil. Signs or symptoms of a hypersensitivity reaction may include: tachypnea, dyspnea, hypoxia, bronchospasm, tachycardia, hypotension, cyanosis, vomiting, nausea, headache, sweating, dizziness, altered mentation, flushing, rash, urticaria, erythema, pyrexia, or chills. If a hypersensitivity reaction occurs, stop infusion of SMOFlipid immediately and undertake appropriate treatment and supportive measures. • Risk of Catheter-Related Infections: Lipid emulsions, such as SMOFlipid, can support microbial growth and is an independent risk factor for the development of catheterrelated bloodstream infections. The risk of infection is increased in patients with malnutrition-associated immunosuppression, long-term use and poor maintenance of intravenous catheters, or immunosuppressive effects of other concomitant conditions or drugs. • Fat Overload Syndrome: This is a rare condition that has been reported with intravenous lipid emulsions. A reduced or limited ability to metabolize lipids accompanied by prolonged plasma clearance may result in a syndrome characterized by a sudden deterioration in the patient’s condition including fever, anemia, leukopenia, thrombocytopenia, coagulation disorders, hyperlipidemia, fatty liver infiltration (hepatomegaly), deteriorating liver function, and central nervous system manifestations (e.g., coma). • Refeeding Syndrome: Reintroducing calories and protein to severely undernourished patients with PN may result in the refeeding syndrome, characterized by the intracellular shift of potassium, phosphorus, and magnesium as the patient becomes anabolic. Thiamine deficiency and fluid retention may also develop.

Fresenius Kabi USA, LLC Three Corporate Drive, Lake Zurich, IL 60047 Phone: 1.888.386.1300 www.fresenius-kabi.com/us

specialist in hematology/oncology at the Kellogg Cancer Center of NorthShore University Health System, in Chicago. “The availability of drugs to target driver mutations has increased tumor response rates and survival. However, cancer cells continue to mutate beyond the driver mutation, yielding resistance mechanisms to our targeted therapies,” Dr. Kapolas told Pharmacy Practice News in advance of a presentation on the topic

• Aluminum Toxicity: SMOFlipid contains no more than 25 mcg/L of aluminum. During prolonged PN administration in patients with renal impairment, the aluminum levels in the patient may reach toxic levels. Preterm infants are at greater risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum. Patients with renal impairment, including preterm infants, who receive parenteral intakes of aluminum at greater than 4 to 5 mcg/kg/ day can accumulate aluminum to levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration of PN products. • Risk of Parenteral Nutrition-Associated Liver Disease (PNALD): PNALD has been reported in patients who receive PN for extended periods of time, especially preterm infants, and can present as cholestasis or steatohepatitis. The exact etiology is unknown and is likely multifactorial. Intravenously administered phytosterols (plant sterols) contained in plant-derived lipid formulations have been associated with development of PNALD, although a causal relationship has not been established. If SMOFlipid-treated patients develop liver test abnormalities, consider discontinuation or dose reduction. • Hypertriglyceridemia: Impaired lipid metabolism with hypertriglyceridemia may occur in conditions such as inherited lipid disorders, obesity, diabetes mellitus, and metabolic syndrome. • Monitoring/Laboratory Tests: Routinely monitor serum triglycerides, fluid and electrolyte status, blood glucose, liver and kidney function, blood count including platelets, and coagulation parameters throughout treatment. Monitoring patients for signs and symptoms of essential fatty acid deficiency (EFAD) is recommended. • Interference with Laboratory Tests: Content of vitamin K may counteract anticoagulant activity. The lipids contained in this emulsion may interfere with some laboratory blood tests (e.g., hemoglobin, lactate dehydrogenase [LDH], bilirubin, and oxygen saturation) if blood is sampled before lipids have cleared from the bloodstream. ADVERSE REACTIONS Most common adverse drug reactions >1% of patients who received SMOFlipid from clinical trials were nausea, vomiting, hyperglycemia, flatulence, pyrexia, abdominal pain, increased blood triglycerides, hypertension, sepsis, dyspepsia, urinary tract infection, anemia and device-related infection. Less common adverse reactions in ) 1% of patients who received SMOFlipid were dyspnea, leukocytosis, diarrhea, pneumonia, cholestasis, dysgeusia, increased blood alkaline phosphatase, increased gamma-glutamyltransferase, increased C-reactive protein, tachycardia, liver function test abnormalities, headache, pruritis, dizziness, rash and thrombophlebitis. The following adverse reactions have been identified during post-approval use of SMOFlipid in countries where it is registered. Infections and Infestations: infection. Respiratory, Thoracic and Mediastinal Disorders: dyspnea. To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176, option 5, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. DRUG INTERACTIONS Coumarin and Coumarin Derivatives, Including Warfarin: Anticoagulant activity may be counteracted; monitor laboratory parameters. USE IN SPECIFIC POPULATIONS • Pregnancy and Lactation: There are no available data on risks associated with SMOFlipid when used in pregnant or lactating women. • Pediatric Use: The safety and effectiveness of SMOFlipid have not been established in pediatric patients. • Hepatic Impairment: Parenteral nutrition should be used with caution in patients with hepatic impairment. Hepatobiliary disorders are known to develop in some patients without preexisting liver disease who receive PN, including cholestasis, hepatic steatosis, fibrosis and cirrhosis (PN associated liver disease), possibly leading to hepatic failure. OVERDOSAGE In the event of an overdose, fat overload syndrome may occur. Stop the SMOFlipid infusion until triglyceride levels have normalized. The effects are usually reversible by stopping the lipid infusion. If medically appropriate, further intervention may be indicated. Lipids are not dialyzable from serum.

at the 2022 annual meeting of the Hematology/Oncology Pharmacy Association, in Boston. “At present, we use NGS to help determine our initial therapeutic approach for targeted therapy, but can we continue to use precision medicine to provide subsequent targeted therapies to patients with resistance mechanisms?” There are several common resistance pathways for various tumor types. “For example, with NSCLC, we initially had the first-generation epidermal growth factor receptor [EGFR] TKIs, such as gefitinib [Iressa, AstraZeneca] and erlotinib [Tarceva, Genetech], and then the secondgeneration agents, afatinib [Gilotrif, Boehringer Ingelheim] and dacomitinib [Vizimpro, Pfizer],” Dr. Kapolas said. “But most patients treated with these first- and second-generation agents develop resistance, with the most common being the EGFRT790M mutation in exon 20.” In November 2015, the FDA approved osimertinib (Tagrisso, AstraZeneca) for the treatment of metastatic NSCLC in patients with T790M mutation-positive NSCLC who had progressed after initial EGFR TKI therapy. In April 2018, that approval was expanded to include

CAR-T ROLLOUT continued from page 19

patients (89%) received their cells as outpatients and 8% remained outpatient for the entire month, with a median time to admission of two days (range, 0-25 days) (J Clin Oncol 2021;39[15 suppl]:7554-7554). A University of Pennsylvania study found that 28 of 30 tisagenleleucel patients (93%) received cells on an outpatient basis, with 32% requiring admission and a median time to admission of five days (range, one to seven days) (Blood 2019;134[suppl 1]:3240). Dr. McGann said her own experiences dovetail with some of the successes seen in these two trials. “Although many of our CAR T-cell patients eventually are admitted,” she said, “by keeping them outpatient until signs of toxicity or other indications develop, we are able to decrease length of stay, decrease costs and increase patient satisfaction.”

Dr. McGann reported no relevant financial disclosures.

Focus on Oncology 21

Pharmacy Practice News • March 2022

first-line treatment of NSCLC exon 19 deletions or exon 21 L858R mutations, based on the results of the phase 3 FLAURA trial, which showed the superiority of osimertinib over first-generation EGFR TKIs as a first-line treatment (Front Oncol 2020;10:602762). “Chronic myelogenous leukemia [CML] is another example of missense mutations acquired during active therapy,” noted Dr. Kapolas, referring to a type of mutation that occurs due to a DNA error that results in the wrong amino acid being incorporated into a protein. “We will typically start CML patients on imatinib [Gleevec, Novartis], nilotinib [Tasigna, Novartis], bosutinib [Bosulif, Pfizer] or dasatinib [Sprycel, Bristol Myers Squibb].” The BCR-ABL1 fusion gene is a strong driver mutation in CML, and BCR-ABL TKIs prevent the BCR-ABL protein from exerting its role in the oncogenic pathway in CML. “Eventually, the BCR-ABL gene may acquire missense mutations. Here, common missense mutations include the V299L mutation and the T3151 mutation; these are typically resistant to many of the BCR-ABL TKIs on the market. We have found that second-generation TKIs have improved our ability to achieve high response rates, with various mutations due to increased binding affinity within the ATP binding pocket, except for the T315I mutation.” T3151 confers resistance to all approved BCR-ABL TKIs, with the exception of ponatinib (Iclusig, Takeda), which has a boxed warning for cardiovascular events and liver toxicity. But in October 2021, the FDA approved asciminib (Scemblix, Novartis), known as a STAMP (specifically targeting the ABL myristoyl pocket) inhibitor, for patients who have CML with the T3151 mutation. “It still targets the BCR-ABL mutation, but at an allosteric site,” Dr. Kapolas said.

acquired resistance pathway as a potential target?” he asked. “That is done right now, with exceptions. When progression occurs while on a first-generation EGFR TKI in metastatic NSCLC, a liquid biopsy might identify a T790M mutation, and if present, that patient would be switched to osimertinib. But if the patient’s first-line treatment is osimertinib, the T790M mutation isn’t likely to occur. Instead, a different alteration, such as mesenchymal epithelial transition [MET] amplification, may result.” As an example, he cited the May

2021 approval of amivantamab-vmjw (Rybrevant, Janssen), a bispecific monoclonal antibody directed against EGFR and MET receptors in locally advanced or metastatic NSCLC with exon 20 mutations. Researchers are using different cohorts of CHRYSALIS to combine amivantamab-vmjw with the thirdgeneration TKI lazertinib in patients who have developed resistance to osimertinib. The goal “is to see if we can overcome those resistance mechanisms instead of moving to chemotherapy,” Dr. Kapolas said.

Dr. Kapolas reported no relevant financial disclosures.

TESTED WITH HAZARDOUS DRUGS BECAUSE YOUR SAFETY IS OUR PRIORITY Unlike other closed system transfer devices (CSTD), OnGuard 2 Closed System Transfer Device locks with a “click” during handling, so there’s no question you’re protected. Only OnGuard 2 was tested with actual hazardous drugs for vapor containment and is the market leader in CSTD air-cleaning technology. Designed to provide simple, safe, and easy-to-use protection for healthcare workers. /HDUQ PRUH DW EEUDXQXVD FRP RQJXDUG

ONGUARD® 2 CSTD DESIGNED FOR THE REAL WORLD.

NEW 0RGLƃ HG UDZ PDWHULDO WR LPSURYH FRPSDWLELOLW\ ZLWK NQRZQ KD]DUGRXV GUXJV 1RW PDGH ZLWK '(+3 RU 39& GD\ PLFURELDO LQJUHVV WHVWLQJƛ

New Treatment Strategies Needed Dr. Kapolas suggested considering new approaches—including the use of NGS testing—when targeting these tyrosine kinase mutations. “Since we have TKIs on the market that target some of the resistance pathways, should we obtain another NGS test upon progression on active treatment to identify any

“As NGS is becoming more and more available, the future of treating cancer with actionable mutations lies with using NGS upon progression to identify resistance pathways to target,” he added. “If we can further identify mutations causing resistance and target one or more pathways simultaneously, we may be able to outsmart the trickery of the tumor cells, extending progression-free survival and ultimately overall survival.”

1) Chemfort Instructions for Use OnGuard 2 CSTD is manufactured by Simplivia Healthcare Ltd. and distributed by B. Braun Medical Inc. Rx only. ©2022 B. Braun Medical Inc. Bethlehem PA. All rights reserved. 22-0931_1/22

22 Clinical

Pharmacy Practice News • March 2022

Pain Management

Pharmacist-Led Program Cuts ED Visits for OUD Stocking treatments in ADCs, boosting X-waivered physicians among key strategies By Gina Shaw

n opioid use disorder (OUD) initiative led by emergency department (ED) pharmacists contributed to a decrease in OUD-related ED visits at Boston Medical Center (BMC) over three years, even as such visits were on the rise nationwide, according to a study presented at the ASHP 2021 Midyear Clinical Meeting and Exhibition, held virtually.

She noted that up to 9% of patients die within a year after a nonfatal overdose—20% of which occurred within one month. At BMC, a multidisciplinary work group consisting of ED physicians, nurses and pharmacists, addiction medicine physicians, and licensed drug and alcohol counselors developed strategies to improve the treatment of patients with OUD in the ED.

‘This paper really highlights the importance of a multidisciplinary approach to an effort like this.’ —Kyle Weant, PharmD

The initiative focused on improving access to medications for OUD (MOUD)—as well as the opioid overdose reversal agent naloxone—and developing ED-specific guidelines for OUD treatment, the study showed. After implementation, monthly ED visits related to OUD declined from more than 200 in September 2017 to between 150 and 175 visits per month by September 2021, according to the researchers. The results came as ED visits for OUD across the country increased by 10.5% (n=3,486; 95% CI, 4.18%-17.0%) in 2020 compared with 2018 and 2019 (n=3,020 and n=3,285, respectively), according to one study (Ann Emerg Med 2022;79[2]:158-167). The results show “pharmacists are essential to improving access to and treatment for OUD,” the researchers said.

Overcoming Barriers Emergency departments are a common touch point for OUD patients to receive MOUD such as buprenorphine, methadone and naltrexone, which are considered standard-of-care treatments, said Natalija Farrell, PharmD, a pharmacy clinical coordinator in emergency medicine at BMC and an assistant professor of emergency medicine at Boston University School of Medicine. However, “patients encounter multiple barriers to accessing MOUD, including ... stigma, failure to stock buprenorphine at pharmacies and insufficient numbers of DEA [Drug Enforcement Administration] X-waivered providers and opioid treatment programs,” Dr. Farrell said.

Those strategies, which were implemented beginning in September 2018, included: • stocking MOUD in the ED’s automated dispensing cabinets; • providing incentives for ED physicians to obtain DEA X-waivers, which increased the percentage of DEA X-waivered ED providers from approximately 5% to approximately 90%; • daily education from ED pharmacists at morning and evening nursing huddles; • education at the emergency medicine physicians’ educational conferences during Recovery Month each September; and • collaborating with BMC’s substance use disorders bridge clinic, Faster Paths, to allow walk-in availability for patients just discharged from the ED. “This paper really highlights the importance of a multidisciplinary approach to an effort like this,” said Kyle Weant, PharmD, BCPS, a clinical assistant professor in the Department of Clinical Pharmacy and Outcomes Sciences at the University of South Carolina College of Pharmacy, in Columbia, who was not involved in the study. “Pharmacists are helpful not only in terms of the logistics, but the patient education and connecting different entities and disciplines together. Then, of course, you have to have physician prescribers, nurses, social workers and others on board, because they are also integral to this process of identifying patients in need of intervention and echoing the

Natalija Farrell, PharmD, and her emergency department pharmacist colleagues at Boston Medical Center have improved treatment access for patients with OUD.

messaging that we’re trying to deliver to those patients.”

Take-Home Naloxone Program The initiative also focused on ensuring people being treated for OUD had access to the opioid overdose medication naloxone. However, funding became an issue when a state grant for naloxone distribution was not renewed in July 2018. To keep the program going, the working group coordinated with the state board of pharmacy and the outpatient pharmacy to develop a retrospective reimbursement process, which went live in September 2018. Once a week, the ED pharmacy manager brought all naloxone prescriptions to the outpatient pharmacy liaison to submit for reimbursement. According to the study, 88% of the prescriptions were covered by insurance, and the remainder were provided at no cost to the patient due to lack of insurance or insurance copay requirements. By January 2020, ED pharmacists began providing discharged patients with buprenorphine-naloxone take-home kits that included one naloxone 4-mg spray and four buprenorphine-naloxone 8-mg/2-mg films, as well as medication handouts and brochures for the Faster Paths bridge clinic, Dr. Farrell said. She said 76.7% of patients who received the buprenorphine-naloxone take-home kits presented at the bridge

clinic within seven days of discharge, compared with 42.7% who received only a buprenorphine-naloxone prescription (P<0.001). “This, to me, is the biggest takeaway from this project—that providing the patients with the kits was very effective in increasing the likelihood that they would be connected to the bridge clinic,” Dr. Weant said. “In hindsight, of course, that seems like an obvious concept, but it’s something that we unfortunately need to continue to prove to the world, that this is worth doing and worth paying for.”

Doing Better With Funding Although Dr. Weant’s current ED does not provide the take-home kits, his previous practice at the Medical University of South Carolina offered kits with naloxone and were working toward adding buprenorphine. “We were fortunate to have a grant from the state to facilitate that,” he said. “That’s one thing that can be frustrating. As was the experience for the authors of this paper, you can do great programs with funding from the state or some other entity, but then the grant funding runs out. We need to do better as a society about having sustained and recurrent funding for programs like these.” The sources reported no relevant financial disclosures.

24 Clinical

Pharmacy Practice News • March 2022

Infectious Disease

Bat exposure remains an under-recognized risk

2021 Was a Deadly Year for Rabies

By Ethan Covey

ive people died from rabies last year in the United States—the highest single-year total in a decade. Four of the deaths were linked to bat exposure, which remains a dangerously underrecognized vector of disease, according to rabies experts. Three of the deaths, which occurred in Idaho, Illinois and Texas, were included in a CDC report. They took place over a five-week period from Sept. 28 to Nov. 10, 2021 (MMWR Morb Mortal Wkly Rep 2022;71[2]:31-32). The cases included two adults and one child, all of whom had direct contact with a bat, by either collision or biting, within three to seven weeks before symptom onset. Three bat species were involved: • Lasionycteris noctivagans (silver-haired bat) • Tadarida brasiliensis (Mexican free-tailed bat) • Eptesicus fuscus (big brown bat) All three are common in the United States and have been linked to the spread of rabies. None of the patients received postexposure prophylaxis (PEP): two because they did not realize the risk for rabies infection associated with bat exposure, and the third due to anti-vaccination beliefs. The patients died within two to three weeks of developing symptoms. “This report is a sad and important reminder that direct contact with bats is a leading cause of rabies deaths in the U.S.,” said Amber Kunkel, ScD, a CDC Epidemic Intelligence Service officer. “Rabies transmission from bats to humans can be prevented,” Dr. Kunkel said. “People should avoid contact with bats whenever possible. People who have contact with a bat should consult their local health department to determine if they should receive postexposure prophylaxis and to have the bat tested for rabies, if possible.” One of the other cases occurred in an immunocompromised Minnesota man

who was bitten by a bat and received PEP but still died because he could not mount an immune response to the PEP. The final case was a man who was bitten by a rabid dog while traveling and died upon return to the United States.

Is Rabies Risk Increasing? The number of cases is raising questions about whether rates of rabies are increasing in the United States. Although the three deaths investigated in the report match the total number recorded during the preceding 48 months, and the total of five is more than reported since 2011, there are differing opinions regarding whether the risk for rabies is increasing.

but remain undiagnosed and unknown, because almost two-thirds of the time, the doctors never figure out what causes a case of encephalitis. The number of rabies cases, therefore, could be higher.” The inconsistencies in CDC reports are indicative of failures with current rabies surveillance, according to Charles E. Rupprecht, MD, PhD, the CEO of Lyssa Inc. in Lawrenceville, Ga. “The state of our surveillance is not ideal,” he said. “You’d think that in the age of COVID we’d have more real-time reporting. The bottom line is we don’t really have a gauge.” Additionally, “we don’t know whether there are five cases or 50 cases [in the United States],” Dr. Rupprecht said. That

‘This recent spate of cases is a sobering reminder that contact with bats poses a real health risk.’ —Ryan Wallace, DVM “Although these all happened in a short time, they occurred in different states and involved different bat species,” Dr. Kunkel said. “The number of bats tested for rabies and the proportion that test positive have been relatively stable over recent years. (About 24,000 bats were tested for rabies in 2020, and about 1,400 were positive.) These data are not yet available for 2021, but so far we have not noticed any indication that rabies in bats is increasing.” Stephen J. Scholand, MD, an infectious disease specialist in Meriden, Conn., disagreed. “Definitely, it seems the risks of contracting rabies from bats is increasing,” he told Infectious Disease Special Edition, a sister publication to Pharmacy Practice News. “This is what was recognized— what came to the attention of public health authorities. There are probably a number of other cases that are occurring

uncertainty is due, at least in part, to the fact that autopsies are not performed on most people who die in the United States, so the true cause of many deaths might be incorrect, he noted. “The differential diagnosis should include rabies for everybody who has an acute progressive encephalomyelitis suspected of being of viral origin,” he said, “and it’s not.”

Knowledge Gap Part of the challenge of preventing rabies deaths, particularly those associated with bat contact, is that people may not know that exposure to a bat poses a risk for rabies transmission. Bites and scratches also can be very small, and it can be difficult to determine what requires medical attention. “What if you wake up and there is a bat in your bedroom?” Dr. Scholand said. “What if you open your child’s

bedroom door and there is a bat? “Would the average person think that is a rabies risk?” Dr. Scholand continued. “Would they call their doctor or visit the emergency department or urgent care center for that?” Dr. Rupprecht stressed that additional rabies outreach efforts are needed—a difficult task in America’s already constrained healthcare system, where prioritizing and maintaining education and increasing the size of the public health workforce are challenges. According to the CDC, healthcare professionals should be aware of the risks associated with bat exposure, and can turn to health departments for detailed information regarding local risk. “Rabies epidemiology varies geographically inside the United States,” Dr. Kunkel said. “Local and state health departments are very familiar with rabies dynamics in their area, and healthcare providers should not hesitate to contact them for advice on evaluating individuals for postexposure prophylaxis. Rabid bats are present in all states except Hawaii, and any person who has direct contact with a bat should be evaluated for postexposure prophylaxis.”

CDC Cites Progress Ryan Wallace, DVM, a veterinarian and rabies expert in the CDC’s Division of High-Consequence Pathogens and Pathology, also noted that recent cases should not overshadow progress that has been made in reducing human rabies cases. “We have come a long way in the U.S. toward reducing the number of people who become infected each year with rabies,” Dr. Wallace said. “But this recent spate of cases is a sobering reminder that contact with bats poses a real health risk.” Dr. Scholand reported a relationship with Grifols. Drs. Kunkel, Rupprecht and Wallace reported no relevant financial disclosures.

When You Only Have Time For One ... We are

Thanks to you!

The best-read hospital pharmacy publication. *Based on data from Kantar Media, 2021

Sign up @ PharmacyPracticeNews.com/ Registration Get the latest news FREE from the most widely read hospital pharmacy publication in the United States, including multimedia and web-only content, delivered directly to your inbox!

26 Technology

Drug Diversion

Software a Time-Saver continued from page 1

are diverted, face infectious disease risks if their IV drugs are tampered with, or receive inadequate care from the 10% of healthcare workers (HCWs) who may divert drugs for personal use, according to the Joint Commission (bit.ly/3JhHKfI). Although reported incidents have been declining in recent years, drug diversion among HCWs—primarily of opioids—is a significantly underestimated and underreported problem that affects every facility that handles controlled substances, according to the American Nurses Association (bit.ly/3svcaEu). An analysis by Protenus showed that more than 148 million prescription drug doses amounting to $183 million were diverted in the healthcare system in 2019, and that doctors and nurses were responsible for 77% of all reported incidents. Their 2021 analysis showed a steep 60% drop in incidents, owing to COVID-19– related reporting constraints that conceal the true extent of the ongoing diversion problem. (The Protenus analyses can be downloaded at bit.ly/3GTvLDz.)

‘A National Epidemic’ “Misuse and diversion of controlled substances is a national epidemic,” said John S. Clark, PharmD, BCPS, an associate chief pharmacy officer at Michigan Medicine, and a clinical associate professor at University of Michigan College of Pharmacy, in Ann Arbor. “Patient caregivers that have access to controlled substances are at high risk for considering diversion. These caregivers are often pharmacists, pharmacy technicians, nurses and anesthesiologists. To provide safety for patients and their caregivers, robust systems must be in place to reduce the opportunity for diversion.” Tyler Vest, PharmD, BCPS, BCSCP, a pharmacy manager at Duke University Hospital, in Durham, N.C., said the

Articles from the current month’s issue Articles ahead of print • Web-exclusive content Brought to you by the same people who publish

Pharmacy Practice News • March 2022

ability to recognize variance trends in large amounts of hospital data, or conduct timely investigations when drug diversion is suspected, can be overwhelming when using a manual process, especially in large health systems. That’s where resources such as ASHP’s guidelines on preventing controlled substances diversion, which include the use of automation and technology, come in handy, he noted. “When addressing drug diversion in hospital systems, we have a tremendous amount of data that have to be analyzed,” Dr. Vest said. “You have scheduling or personnel data, then the automated dispensing cabinet [ADC] system has another set of data, and then electronic health records [EHRs] generate yet another data set. Until recently, there haven’t been good systems on the market that are able to integrate those three data streams and allow us to have a more comprehensive view in drug diversion management.” Trend analysis is a key benefit of drug diversion software, and the alternative manual process is like trying to find a needle in a haystack, Dr. Vest added. “It’s incredibly difficult to trend data by yourself because it’s an overwhelming amount of data,” he stressed. “Just because you have a discrepancy on a cabinet doesn’t mean something’s diverted; it could be that it was stocked or removed incorrectly, or there was a miscount. But when you are able to integrate all of your data, these systems can prioritize the trends you should look at.”

Vendor Selection at Allina Health Ms. Myrhe and her colleagues at Allina Health—who oversaw 567 ADCs across 12 hospitals and eight emergency medical service bases that generate around 30,000 drug dispensing transactions per day—sought to identify and implement a new drug diversion surveillance

Technology

Pharmacy Practice News • March 2022

Drug Diversion

‘With this new automated documentation audit process and the data analytics this tool provides, our staff can now focus on potential practice concerns sooner, because they are not spending time analyzing data and looking for the issues.’

—JoAnne Myhre, CPhT, FMSHP

application in January 2019. After evaluating six products, the team used a scoring system to decide between two final candidates, with focused criteria for vendor selection. “Although there were several key factors—including cost, reporting capabilities, additional data point opportunities, incident and service turnaround, speed of releasing enhancements, the ability to ‘shrink’ the haystack and bring us closer to the potential diverter—one factor that was key in our decision-making process was how we felt the vendor would work with us,” she said. “Meaning how open were they to listening to us, and how nimble, flexible and responsive would they be to our ideas, questions and concerns?” After selecting their product/vendor— BlueSight for Controlled Substances—and

Resources ASHP Guidelines on Preventing Diversion of Controlled Substances bit.ly/35xqz8v

Institute for Safe Medication Practices Best practices for the safe and costeffective management of controlled substances bit.ly/3oElIMd

Centers for Disease Control and Prevention Injection safety: Drug diversion. November 26, 2019. bit.ly/3HLBxbA

Joint Commission Pellegrini CA. Joint Commission focuses on strategies to detect, prevent drug diversion. Bulletin of the American College of Surgeons. June 1, 2019. bit.ly/3JinMS2

preparing for launch, the team integrated the application into their drug diversion system, and worked with key stakeholders to evaluate audit workflows, improve processes and standardize best practices across their organization.

Key Metrics Six months after implementation, the team used several key metrics to measure improvements, including the “average total percent variance rate,” which dropped from 6.3% to 5.8%. These variances included the proportion of controlled substance ADC and medication administration record (MAR) transaction records that the new application did not reconcile automatically. Ms. Myrhe added that the documentation of medications being given to patients more often matched what was ordered after the application was launched, reducing the amount of nonmatches that would require investigation. “This total variance figure was significant for us, because prior to this new application, we had no data on what our gap in documentation really was, nor were we able to effectively and efficiently find potential trends in the data because a significant part of that workflow was a manual process for us,” Ms. Myhre said. Dr. Clark said although the total variance decrease reported is modest, it can be meaningful at scale. “When you consider some health systems have tens to hundreds of thousands of transactions a year, this impact may be great in number,” he said. Ms. Myrhe and her colleagues also reported that the “time to close documentation variances trending report,” the time spent reconciling open variances between ADC and MAR transaction records, dropped from four to 2.2 days.

“The almost halving of days for resolution of [medication] discrepancy allows for better, more complete follow-up, because practitioners will better remember what occurred,” Dr. Clark said. Finally, the “average time to close investigations report,” the average time

needed to close an audit/investigation, dropped from 49.4 to 7.2 days, which is an efficient number for a large health system, according to Dr. Vest. “Overall, this work shows the importance of analytics in controlled substance diversion prevention and the benefits advanced analytics can provide in learning about potential diversion events,” Dr. Clark said. According to Dr. Vest, drug diversion applications are becoming more commonly adopted in academic medical centers and health systems, and the efficiency improvements detailed in this study should encourage pharmacy leadership teams to evaluate whether such an application would improve their drug diversion surveillance programs. “Consider getting your group together to evaluate these types of applications, whatever your group size is,” he said. “Ultimately, there is so much data, it’s very difficult for a team or individual to look at this without help from advanced analytics that can streamline those workflows and provide tools to create a more efficient diversion program in your hospital.” The sources reported no relevant financial disclosures.

28 Policy

Pharmacy Practice News • March 2022

FDA Watch

FDA Approves Enjaymo for Adults ts With Rare Type of Anemia By PPN News Staff

he FDA approved sutimlimabjome (Enjaymo, Sanofi) infusion to decrease the need for red blood cell transfusion due to hemolysis in adults with cold agglutinin disease (CAD). Sutimlimab-jome, a humanized monoclonal antibody (mAB), is the first and only approved treatment for people with CAD, according to Sanofi.

Sutimlimab-jome was designed esigned to selectively target and inhibit it complement component 1 (C1) in the classic complement pathway, which is part of the innate immune system. By blocking C1s, the mAB inhibits C1-activated hemolysis in patients with CAD to prevent the abnormal destruction of healthy red blood cells.

The FDA considered T the results of the CARDINAL study, a pivotal DI phase 3 single-arm, open-label, 26-week study in patients with st CAD (N=2 (N=24) who had a recent history of blood transfusion. In the study, sutimlimab-jome met the primary efficacy end point—a composite outcome defined as the proportion of patients who achieved normalization of hemoglobin (Hb) level of at least 12 g/dL or demonstrated an increase from

Don’t play games with your workers’ safety Choose a truly closed system that provides the necessary protection for healthcare workers handling hazardous drugs · PROVEN as the only closed system to prevent syringe plunger contamination and accidental

baseline in Hb level of at least 2 g/dL at treatment assessment (mean value from weeks 23, 25 and 26). The composite outcome also included documentation of no blood transfusion from weeks 5 through 26 or medications prohibited per the protocol from weeks 5 through 26. Most patients (54%; n=13) met the composite primary end point criteria, with 63% (n=15) of patients achieving an Hb of at least 12 g/dL or an increase of at least 2 g/dL; 71% (n=17) of patients remained transfusion-free after week 5; and 92% (n=22) of patients did not use other CAD-related treatments. “The relentless destruction of healthy red blood cells is a daily, silent reality for people with CAD,” said Catherine Broome, MD, an associate professor of medicine at Georgetown University Lombardi Comprehensive Cancer Center in Washington, D.C., and a principal investigator in the CARDINAL study. “For the first time, we have a treatment that targets complement-mediated hemolysis, which is the underlying cause of the red blood cell destruction in many CAD patients.” The most common adverse reactions occurring in 10% or more of patients were respiratory tract infection, viral infection, diarrhea, dyspepsia, cough, arthralgia, arthritis and peripheral edema. Serious adverse reactions were reported in 13% (3/24) of patients who received sutimlimab-jome: streptococcal sepsis and staphylococcal wound infection (n=1), arthralgia (n=1) and respiratory tract infection (n=1). None of the adverse reactions led to discontinuation of sutimlimab-jome in the study. The recommended dose of sutimlimab-jome is based on body weight (6,500 mg for weight 39-75 kg; 7,500 mg for weight >75 kg), and is administered intravenously weekly for the first two weeks with administration every two weeks thereafter. The FDA gave sutimlimab-jome breakthrough therapy and orphan drug designations. The prescribing information for the medication can be accessed at bit.ly/3Bovszs. For financial and copay assistance programs and other support services for eligible patients, call (833) 223-2428.

disconnection - standard syringes and their plungers accept contamination with almost every[ WUG CPF use and may cause hazardous drugs (HD) spills with accidental removal of plunger*. TPCN UVGTKNG · RESTRICTS the escape of HD and vapor due to a unique encapsulated syringe with an internal

sterile air chamber and closed pressure equalization system*.

105 ŧ

· ADHERES to all NIOSH Protocols and deﬁnitions of a CSTD, USP <800>, FDA ONB, ISOPP, ONS …*.

GU CU C HWNN[

· PREVENTS disconnection of syringe connector due to a welded connection point that comes as a fully assembled ready to use Syringe Unit for ease of use*.

GZRQUWTG

· NEEDLESAFE fully encased needles and dry connection membranes eliminate HD residue exposure*, needle sticks, and prevent microbial ingress for up to 7 days**.

+1-855-378-2744 | www.equashield.com * Data available on Clinical Data page of EQUASHIELD website. ** EQUASHIELD does not extend the sterility and use date of the drug beyond manufacturer recommendations. Please refer to individual drug labeling or USP compounding guidelines for beyond use dating of a drug

Kimmtrak Takes BiTE Out of Uveal Melanoma

he FDA approved tebentafusp-tebn (Kimmtrak, Immunocore), a bispecific T-cell engager (BiTE) designed to redirect the immune system to recognize and kill cancerous cells, for the treatment of adults with unresectable or metastatic uveal melanoma. FDA News, page 30

Policy

Pharmacy Practice News • March 2022

Reimbursement Issues

Catching up on what’s crucial!

The Waste REFUND Act T

he infrastructure bill that passed on Nov. 15, 2021, garnered much media attention for its focus on bridges and other long-neglected systems. But did you know that the bill also includes a drug waste provision that, if not addressed adequately by your revenue cycle team, could lead to failed audits and charges of healthcare fraud? Fortunately, there are four key questions you can use to determine how to accurately bill for drug waste and ensure compliance, along with several other tools detailed below.

istration instructions included in the labeling require filtration during the drug preparation process, prior to dilution and administration, and require that any unused portion of such drug after the filtration process be discarded after the completion of such filtration process; and • a drug or biological approved by the FDA on or after the date of enactment of this subsection and with respect to which payment has been made under this part for fewer than 18 months. Further provisions require HHS to

area shortly after moving to the concept of “billing units representing actual dose given” for reimbursement and away from the “whole vial” method of billing under OPPS. Medicare does not mandate billing for waste, but makes it possible to recoup some lost dollars if you choose to bill for them. How does this work? That’s where answering those four questions comes in: 1. Is the drug being used for a Medicare outpatient? 2. Are you using a single-dose vial/ package? 3. Does the product have an HCPCS code? 4. Does the code include an SI G or SI K designation? If yes, proceed to waste billing. If no, then there’s nothing to do.

3 Trigger Points To Measure Your Progress 1. Candidate Drugs Success: Eligible SI G + K drugs identified, updated quarterly Fail Point: Pharmacy unaware of how to do this

2. Billing Unit Conversions

First, a bit more background. The portion of the infrastructure bill (H.R. 3684) that you need to pay attention to is the drug waste provision from the Recovering Excessive Funds for Unused and Needless Drugs (REFUND) Act of 2021 (S. 1287). The act requires manufacturers to rebate the amount wasted back to CMS effective Jan. 1, 2023 (see Sec. 90004). This concept was first introduced in 2019 by Sens. Dick Durbin (D-Ill.) and Rob Portman (R-Ohio) in a bipartisan bill designed to reduce egregious wasted spending on discarded medications that are the result of excessively large, single-use drug vials. The bill requires drug companies/ manufacturers to reimburse Medicare for certain wasted medications. It specifically states that these medications are certain single-dose container or single-use package drugs payable under Part B of the Medicare program. The intent is to provide refunds with respect to discarded amounts of such drugs— for example, wasted medications that include leftover portions of drugs packaged in single-use containers. Keep in mind, however, that three pharmaceutical categories are excluded: • a drug or biological that is either a radiopharmaceutical or an imaging agent; • a drug or biological approved by the FDA for which dosage and admin-

aggregate the total amount of discarded Part B drugs quarterly using Medicare Part B claims and calculate refunds using the ASP (or WAC if ASP is not available). The drug manufacturer will be required to provide a rebate to HHS for the total amount of discarded medication recorded, above a 10% low-volume threshold. Noncompliance to provide a timely rebate could incur civil monetary penalties under this act. More details on S. 1287 and H.R. 3684 can be found at the Congress. gov website (bit.ly/35ZG4Jo and bit. ly/3spjqBH, respectively). For the latter, see Sec. 90004, which requires certain single-dose container or singleuse package drugs payable under Part B of the Medicare program to provide refunds with respect to discarded amounts of such drugs. Compliance audits are a guarantee! These could be audits of the manufacturer’s compliance, as well as audits of health systems’ activities related to the accuracy of the aggregated amount calculated, comparisons of billed doses and billed wastage with the number of units sold, or any untold number of other methods of determining data accuracy and ruling out fraud. Given the potential for audits, this is a good time to review your waste billing program. Medicare created the ability to bill for expensive waste in the outpatient

Success: Crosswalk accurate, CDM/PDM built to accommodate required charting Fail Point: Pharmacy not following up

3. Reality Matches Billing Success: Clinician actions match charting and billing Fail Point: Pharmacy opted for “robo-billing.” Billing person has no idea of what clinician or IV prep area actually did See Module 4 of the Reimbursement Tool Kit (www.pharmacypracticenews.com/ToolKit) for more e details.

It’s also important to avoid pitfalls when coding for drug waste. For example, the actions in the IV prep area must match what’s billed and charted in the EHR! Don’t file build in such a way that the computer automatically processes waste billing on order entry without knowing exactly what’s happening to the drug. Never create an auto-bill situation that doesn’t represent true actions. Consider this potentially tricky filebuild scenario: The drug vial contains 1 g of medication. The infusion center uses 500 mg for each of two patients.

“Reimbursement Matters” is a tool for maintaining your health system’s fiscal health. Please email the author at bonniekirschenbaum@ gmail.com with suggestions on reimbursement issues that you would like to see covered.

Bonnie Kirschenbaum, MS, FASHP, FCSHP

A Reimbursement Lexicon ASP, average sales price; CDM, charge description master; CMS, Centers for Medicare & Medicaid Services; EHR, electronic health record; HCPCS, Healthcare Common Procedure Coding System; HHS, Department of Health and Human Services; MAR, medication administration record; OPPS, Outpatient Prospective Payment System; PDM, pharmacy drug master; SI, status indicator; WAC, wholesale acquisition cost

Nothing was actually wasted. But without a careful file build, you could have created a situation where your revenue cycle department would assume that two vials had been used and erroneously process two waste charges. This would constitute fraud. Zero-priced products are another potential pitfall. These medications— typically patient assistance and whitebagged/specialty pharmacy drugs— don’t qualify for waste billing. Since there’s no charge for these products because you didn’t buy them, there cannot be any waste billed. Staff must understand the difference, know when a zero-priced product is being used and use the correct line item on order entry. It’s also important to understand your system’s limitations. For instance, you may be able to file build such that the computer will calculate the amount given and amount wasted, but how does this information become a line on the MAR for the nurse to chart the waste? And how does this information get converted into a waste line bill with the appropriate modifier that accompanies the drug line bill so that the two are charged together on the same day? Documentation must be in the patient chart; automated dispensing records or other internal pharmacy records aren’t sufficient. If you’re trying to charge for waste for something that comes out of an automated dispensing cabinet, you’ll need to work out how this is consistently charted in the medical record, if that is even possible. Here’s another important tip: Don’t forget about revenue cycle orientation. Waste billing means that there are two lines of billing for the same patient on the same day with the waste identified by the JW modifier. This goes completely against the hard stops that have been built into many of the revenue cycle processes that prevent this from happening. Have you worked with your revenue cycle team to resolve this issue? ■

30 Policy

Pharmacy Practice News • March 2022

FDA Watch

FDA NEWS continued from page 28

Tebentafusp-tebn is the first T-cell receptor (TCR) therapeutic to receive regulatory approval from the FDA and the first BiTE approved to treat a solid tumor, Immunocore said in a press release. It also is the only therapy approved to treat this rare form of ocular melanoma, the company said (bit.ly/3uaTXyt). “Uveal melanoma is a devastating disease that has historically resulted in death within a year of metastasis for our patients,” John Kirkwood, MD, the director of the Melanoma Center at the University of Pittsburgh Hillman Cancer Center, said in the press release. “The approval … represents a major paradigm shift in the treatment of metastatic uveal melanoma, and for the first time offers hope to those with this aggressive form of cancer.” The approval was based on a phase 3 trial of 378 human leukocyte antigen (HLA)-A*02:01–positive adults who received tebentafusp-tebn or the investigator’s choice of therapy with single-agent dacarbazine, ipilimumab or pembrolizumab, according to results published in The New England Journal of Medicine (2021;385[13]:1196-1206). Overall survival at one year was 73% in the tebentafusp-tebn group and 59% in the control group (hazard ratio [HR] for death, 0.51; 95% CI, 0.37-0.71; P<0.001). Progression-free survival at six months was 31% in the tebentafusptebn group compared with 19% (HR for disease progression or death, 0.73; 95% CI, 0.58-0.94; P=0.01). Serious adverse reactions include cytokine release syndrome (CRS); skin reactions such as rash, pruritus and cutaneous edema; and elevations in liver enzymes, Immunocore said. Other common side effects include fatigue, nausea, hypotension, dry skin, headache and vomiting. Tebentafusp-tebn is a new class of BiTE therapy that specifically targets the lineage antigen glycoprotein 100 via an anti–cluster-of-differentiation 3 immune-activating effector function, Immunocore said. The compound is an example of Immunocore’s proprietary TCR technology, which generates bispecific biologics called ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) molecules, according to the company. “Based on the demonstrated mechanism of T-cell infiltration into human tumors, the ImmTAC mechanism of action holds the potential to treat hematologic and solid tumors, regardless of mutational burden or immune infiltration, including immune ‘cold’ low mutation rate tumors,” Immunocore said. “The approval of tebentafusp-tebn is very exciting, because it represents

the first treatment for patients with unresectable or metastatic uveal melanoma, a devastating disease,” said Lisa Holle, PharmD, BCOP, a clinical professor of pharmacy practice in the Department of Pharmacy Practice, University of Connecticut School of Medicine, in Storrs. “Incorporating this new medication, however, into patient care will require education of the healthcare team, especially for those who may not be familiar with BiTE therapies,” added Dr. Holle, a member of the Pharmacy Practice News editorial board.

BiTE therapies can cause CRS, “which can be very serious and even lifethreatening, requiring close monitoring for at least 16 hours the first three infusions,” Dr. Holle said. “This represents a challenge for infusion rooms, which typically are not operating for that length of time on a daily basis. Thus, observation in an inpatient setting may be needed.” She added that “a trained healthcare team should be available with access to the appropriate medications and equipment to manage CRS. Pharmacists should ensure that patients are euvolemic prior

to starting therapy, as well.” Other potential toxicities, Dr. Holle noted, include skin reactions, “which are common but often can be managed with antihistamines and topical corticosteroids, and elevations in hepatic enzymes, which should be monitored closely during therapy.” For more news on BiTE therapy, see page 17

Policy

Pharmacy Practice News • March 2022

FDA Watch

FDA Warns of Strangulation Risk From Tubes By PPN News Staff

nteral feeding set tubing can become wrapped around a child’s neck, causing strangulation or death, the FDA warned pharmacists, parents and other healthcare professionals. The warning comes after the FDA received reports of two toddlers younger than 24 months who died after being strangled by the tubing last year, the agency said. “While the FDA believes that death or

serious injury from strangulation with enteral feeding set tubing in children is rare, health care providers and caregivers should be aware that these events can and do occur,” the FDA said. “It is also possible that some cases have not been reported to the FDA.” The FDA recommends pharmacists and other healthcare workers share the warning with colleagues and pediatric patient caregivers to ensure they are taking appropriate measures to protect

patients, including following protocols to monitor medical line safety. Adverse events related to enteral feeding set tubing can be reported to the FDA’s MedWatch system online (bit. ly/34SQE4f ). “Prompt reporting of adverse events can help the FDA identify and better understand the risks associated with medical devices,” the FDA said. The agency added it is working with device manufacturers to evaluate the risk

in pediatric patients and to create strategies to minimize patient risk. Almost 190,000 pediatric patients— 40% of all users—rely on feeding tubes for nutrition in the United States, according to a 2017 study (Nutr Clin Pract 2017;32[6]:799-805). Find more information, including safety tips and other resources, on the Feeding Tube Awareness Foundation website (www.feedingtubeawareness.org).

Pharmacy Practice News - March 2022

Articles inside

Cracks in COVID-19 trials still showing

waste?

emergency

orders

certification