JHOP March 2015 | Vol 5 | No 1 by The Oncology Pharmacist

march 2015 Vol 5 I No 1

Journal OF

hematology Oncology ™ Pharmacy The Peer-Reviewed Forum for Oncology Pharmacy Practice

Editorial

Adverse Event Recognition and Management in Practice and on Clinical Trials R. Donald Harvey, PharmD, FCCP, BCOP Original Research

Pharmacist-Run Vaccination and Medication Management Service for Patients After Bone Marrow Transplant Simon Pence, PharmD; Robert Mancini, PharmD, BCOP

CLAG/CLAG-M in Patients with Relapsed/Refractory Acute Myeloid Leukemia Christan M. Thomas, PharmD; Cindy Ippoliti, PharmD; Eric Feldman, MD Symptom management overview

Prevention and Treatment of Cytarabine-Induced Keratoconjunctivitis By Joseph Bubalo, PharmD, BCPS, BCOP From the Literature

Concise Reviews of Studies Relevant to Hematology Oncology Pharmacy With commentaries by Robert J. Ignoffo, PharmD, FASHP, FCSHP

WWW.JHOPONLINE.COM

Innovations in Oncology Management A newsletter series for oncology practice administrators, administrative staff, advanced practice clinicians, and oncology pharmacists. The series will provide concise, up-to-date information on current issues that are impacting the business of oncology.

Good Manufacturing Process

Topics include: Part 1: Patient Support Services Part 2: Oral Parity Legislation Part 3: Emerging Payment and Delivery Models Part 4: Working Collaboratively with Local Payers TO VIEW THE SERIES ONLINE PLEASE LOG ON TO:

InnovationsInOncologyManagement.com anagement.com Supported by funding from Celgene Corporation and Celgene Patient Support. Manufacturer did not influence content. EHC388 Innovations ASize_120214

Publishing Staff

Senior Vice President/Group Publisher Nicholas Englezos nenglezos@the-lynx-group.com Vice President/Group Publisher Russell Hennessy rhennessy@the-lynx-group.com Vice President/Director of Sales & Marketing Joe Chanley jchanley@the-lynx-group.com Publisher Cristopher Pires cpires@the-lynx-group.com Editorial Directors Dalia Buffery dbuffery@the-lynx-group.com Frederique H. Evans fevans@the-lynx-group.com Copyeditor Hina Khaliq Senior Production Manager Lynn Hamilton

The LYNX Group President/CEO Brian Tyburski

Chief Operating Officer Pam Rattananont Ferris Vice President of Finance Andrea Kelly Director, Human Resources Jennine Leale Director, Strategy & Program Development John Welz Director, Quality Control Barbara Marino Quality Control Assistant Theresa Salerno Director, Production & Manufacturing Alaina Pede Director, Creative & Design Robyn Jacobs Creative & Design Assistants Lora LaRocca Wayne Williams Director, Digital Media Anthony Romano

March 2015 Journal OF

hematology Oncology Pharmacy™ The Peer-Reviewed Forum for Oncology Pharmacy Practice

Table of Contents Editorial 6 Adverse Event Recognition and Management in Practice and on

Clinical Trials R. Donald Harvey, PharmD, FCCP, BCOP

Original Research 8 Pharmacist-Run Vaccination and Medication Management Service

for Patients After Bone Marrow Transplant Simon Pence, PharmD; Robert Mancini, PharmD, BCOP

LAG/CLAG-M in Patients with Relapsed/Refractory Acute C Myeloid Leukemia Christan M. Thomas, PharmD; Cindy Ippoliti, PharmD; Eric Feldman, MD 17

departments

Symptom Management Overview 12 Prevention and Treatment of Cytarabine-Induced Keratoconjunctivitis By Joseph Bubalo, PharmD, BCPS, BCOP From the Literature 21 Concise Reviews of Studies Relevant to Hematology Oncology Pharmacy With commentaries by Robert J. Ignoffo, PharmD, FASHP, FCSHP

Jr Digital Media Specialist Charles Easton IV Web Content Manager Anthony Trevean Digital Programmer Michael Amundsen Meeting & Events Planner Linda Mezzacappa Project Manager Deanna Martinez Project Coordinator Rachael Baranoski IT Manager Kashif Javaid Administrative Team Leader Allison Ingram Administrative Assistant Amanda Hedman Office Coordinator Robert Sorensen Green Hill Healthcare Communications 1249 South River Road – Ste 202A Cranbury, NJ 08512 Phone: 732-656-7935 • Fax: 732-656-7938

Vol 5, No 1

March 2015

Volume 5, number 1

MISSION STATEMENT The Journal of Hematology Oncology Pharmacy is an independent, peer-reviewed journal founded in 2011 to provide hematology and oncology pharmacy practitioners and other healthcare professionals with high-quality peer-reviewed information relevant to hematologic and oncologic conditions to help them optimize drug therapy for patients. Journal of Hematology Oncology Pharmacy™, ISSN 2164-1153 (print); ISSN 2164-1161 (online), is published 4 times a year by Green Hill Healthcare Communications, LLC, 1249 South River Rd, Suite 202A, Cranbury, NJ 08512. Telephone: 732.656.7935. Fax: 732.656.7938. Copyright © 2015 by Green Hill Healthcare Communications, LLC. All rights reserved. Journal of Hematology Oncology Pharmacy™ logo is a trademark of Green Hill Healthcare Communications, LLC. No part of this publication may be reproduced or transmitted in any form or by any means now or hereafter known, electronic or mechanical, including photocopy, recording, or any informational storage and retrieval system, without written permission from the Publisher. Printed in the United States of America. EDITORIAL CORRESPONDENCE should be addressed to EDITORIAL DIRECTOR, Journal of Hematology Oncology Pharmacy™, 1249 South River Rd, Suite 202A, Cranbury, NJ 08512. E-mail: JHOP@greenhillhc.com. YEARLY SUBSCRIPTION RATES: United States and possessions: individuals, $105.00; institutions, $135.00; single issues, $17.00. Orders will be billed at individual rate until proof of status is confirmed. Prices are subject to change without notice. Correspondence regarding permission to reprint all or part of any article published in this journal should be addressed to REPRINT PERMISSIONS DEPARTMENT, Green Hill Healthcare Communications, LLC, 1249 South River Rd, Suite 202A, Cranbury, NJ 08512. The ideas and opinions expressed in Journal of Hematology Oncology Pharmacy™ do not necessarily reflect those of the Editorial Board, the Editorial Director, or the Publisher. Publication of an advertisement or other product mentioned in Journal of Hematology Oncology Pharmacy™ should not be construed as an endorsement of the product or the manufacturer’s claims. Readers are encouraged to contact the manufacturer with questions about the features or limitations of the products mentioned. Neither the Editorial Board nor the Publisher assumes any responsibility for any injury and/or damage to persons or property arising out of or related to any use of the material contained in this periodical. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosage, the method and duration of administration, or contraindications. It is the responsibility of the treating physician or other healthcare professional, relying on independent experience and knowledge of the patient, to determine drug dosages and the best treatment for the patient. Every effort has been made to check generic and trade names, and to verify dosages. The ultimate responsibility, however, lies with the prescribing physician. Please convey any errors to the Editorial Director.

Journal of Hematology Oncology Pharmacy

www.JHOPonline.com

Editorial Board

Co-Editors-In-Chief Patrick J. Medina, PharmD, BCOP Associate Professor Department of Pharmacy University of Oklahoma College of Pharmacy Oklahoma City, OK

Val R. Adams, PharmD, FCCP, BCOP Associate Professor, Pharmacy Program Director, PGY2 Specialty Residency Hematology/Oncology University of Kentucky College of Pharmacy Lexington, KY

Section Editors Clinical Controversies

Original Research

Practical Issues in Pharmacy Management

Review Articles

Christopher Fausel, PharmD, BCPS, BCOP Clinical Director Oncology Pharmacy Services Indiana University Simon Cancer Center Indianapolis, IN

R. Donald Harvey, PharmD, FCCP, BCPS, BCOP Associate Professor, Hematology/Medical Oncology Department of Hematology/Medical Oncology Director, Phase 1 Unit Winship Cancer Institute Emory University Atlanta, GA Scott Soefje, PharmD, MBA, BCOP Director of Pharmacy University Medical Center Brackenridge Austin, TX

Timothy G. Tyler, PharmD, FCSHP Director of Pharmacy Comprehensive Cancer Center Desert Regional Medical Center Palm Springs, CA

From the Literature

Robert J. Ignoffo, PharmD, FASHP, FCSHP Professor of Pharmacy, College of Pharmacy Touro Universityâ&#x20AC;&#x201C;California Mare Island, Vallejo, CA

Symptom management overview

Joseph Bubalo, PharmD, BCPS, BCOP Assistant Professor of Medicine Division of Hematology and Medical Oncology Oncology Clinical Pharmacy Specialist OHSU Hospital and Clinics Portland, OR

editors-At-Large

Sandra Cuellar, PharmD, BCOP Director Oncology Specialty Residency University of Illinois at Chicago Medical Center Chicago, IL

Steve Stricker, PharmD, MS, BCOP Assistant Professor of Pharmacy Practice Samford University McWhorter School of Pharmacy Birmingham, AL

Robert Mancini, PharmD, BCOP Oncology Pharmacist PGY2 Oncology Residency Director St. Lukeâ&#x20AC;&#x2122;s Mountain States Tumor Institute Boise, ID

John M. Valgus, PharmD, BCOP, CPP Hematology/Oncology Senior Clinical Pharmacy Specialist University of North Carolina Hospitals and Clinics Chapel Hill, NC

Sachin Shah, PharmD, BCOP Associate Professor Texas Tech University Health Sciences Center Dallas, TX

Daisy Yang, PharmD, BCOP Clinical Pharmacy Specialist The University of Texas M. D. Anderson Cancer Center Houston, TX

Journal of Hematology Oncology Pharmacy

www.JHOPonline.com

March 2015

Vol 5, No 1

Managed Care Payers and Pharmaceutical Oncology Trends

John Fox, MD, MHA Senior Medical Director Associate Vice President Medical Affairs Priority Health

Alex Jung Principal, Global Strategic Advisory Services Ernst & Young LLP

Omni Shoreham Hotel • Washington, DC TH

ANNUAL CONFERENCE

RSARY VE NI

AGENDA

MAY 4, 2015

7:00 am – 8:00 am

Meet the Experts Breakfast

8:00 am – 8:15 am

Introduction to Conference and Opening Remarks John Fox, MD, MHA, Priority Health Alex Jung, Ernst & Young LLP

8:15 am – 9:00 am

Session 1 - The Emerging Role of Personal Medicine – the Business Case Vince Miller, MD, Foundation Medicine

9:00 am – 9:45 am

Session 2 - Pathways versus Personalized Medicine – Never the Twain Shall Meet Michael Kolodziej, MD, Aetna

9:45 am – 10:00 am

Break

10:00 am – 10:45 am

Session 3 - The CMMI Multipayer Oncology Care Model Heidi Schumacher, MD, CMMI

10:45 am – 11:30 am

Session 4 - Practice Accreditation as Oncology Medical Homes Ted Okon, Community Oncology Alliance (Invited) David Eagle, Community Oncology Alliance (Invited)

11:30 am – 12:15 pm

12:15 pm – 1:15 pm

Session 5 - How to Measure Quality in Cancer Michael Kolodziej, MD, Aetna Heidi Schumacher, MD, CMMI David Eagle, Community Oncology Alliance (Invited) Ted Okon, Community Oncology Alliance (Invited) Lunch Presentation - Financial Toxicity Speaker TBD

1:15 pm – 2:00 pm

Session 6 - Keynote Session – IMS Oncology Drug Trends Report Doug Long, IMS Health Inc

2:00 pm – 2:45 pm

Session 7 - Pharma and Defining Value in Cancer Care Sanjeev Wadhwa, Biologist/Life Sciences Consultant for R&D

2:45 pm – 3:30 pm

Session 8 - Comparative Effectiveness and Measuring Value of Drug Therapeutic Options in Cancer Care Robert Bilkovski, MD, Abbott Pharmaceuticals

3:30 pm – 4:15 pm

Session 9 - Perspective on the Future of Oncology Drug and Disease Management Grant Lawless, RPh, MD, FACP, University of Southern California

4:15 pm – 5:00 pm

Session 10 - Limited Distribution Oncology Drug Networks and the Value of Controlled Distribution Alex Jung, Ernst & Young LLP

5:00 pm – 5:45 pm

Session 11 - Specialized Pharmacy and Adding Value of Disease and Patient’s Support in Cancer Care Speaker TBD

5:45 pm – 6:00 pm

Poster Award Q & A

6:00 pm – 6:15 pm

Closing Remarks

6:15 pm – 8:15 pm

Welcome Reception/Exhibit Hall

*Agenda subject to change. AVBCC395_Agenda4Asize021215

AVBCConline.org/conference

EDITORIAL

Adverse Event Recognition and Management in Practice and on Clinical Trials Translating the Common Terminology Criteria for Adverse Events

R. Donald Harvey, PharmD, FCCP, BCOP Section Editor, Original Research, Journal of Hematology Oncology Pharmacy, Associate Professor, Hematology/Medical Oncology; Director, Phase 1 Clinical Trials Section, Winship Cancer Institute of Emory University, Atlanta, GA

s pharmacists, we play an integral role in anticipating and managing adverse events associated with conventional and novel cancer treatments. From alkylating agents to programmed cell death-1 receptor antagonists, the sheer number of agents, spectrum of toxicities, and rapidly evolving combination data make it difficult to maintain an up-to-date approach to treating patients who are at risk for adverse events. Primary literature, abstracts, and other sources of clinical trial data such as ClinicalTrials.gov are valuable resources for clinicians to evaluate when prospectively considering side effect frequency, severity, and prevention strategies. In this issue of the Journal of Hematology Oncology Pharmacy, Joseph Bubalo, PharmD, BCPS, BCOP, provides an overview of the mechanism, prophylaxis, and evidence for the management of a common clinical question posed to pharmacists—cytarabine-induced keratoconjunctivitis (see “Prevention and Treatment of Cytarabine-Induced Keratoconjunctivitis,” on page 13). This example provides an opportunity to consider how the Common Terminology Criteria for Adverse Events (CTCAE) may be applied to daily practice. Reviewing the CTCAE reminds us that, generally, the grading of adverse events is an attempt to describe the clinical severity of a sign, symptom, or disease defined as an unintended or unfavorable event that may be asso ciated with a procedure or medical treatment (Table).1 Looking at conjunctivitis as a root term in the CTCAE, it is graded from 1 to 3, with similarities to general grades listed in the Table. Specifically, grade 2 is listed as “symptomatic; topical intervention indicated (eg, antibiotics); limiting instrumental [activities of daily living].”1 Clinically, this grading suggests a patient who has clear evidence of impairment (eg, redness, pain), and who, in all likelihood, would describe this as at least bothersome if not debilitating. A key caveat to the CTCAE is that a semicolon should functionally be in-

Journal of Hematology Oncology Pharmacy

terpreted as “or,” meaning any one of the descriptors makes it a grade 2. The challenge of CTCAE use has an impact on both clinical trial data reporting and interpretation. If this were a patient on a trial who was asymptomatic yet empirically given eyedrops, it automatically becomes a grade 2 toxicity based on the intervention. In clinical trial conduct, we often forget that what we do to/for patients may have an effect on toxicity grade. Similar examples and potential clinical scenarios of toxicity upgrades can be seen throughout the CTCAE in areas of importance to pharmacists, such as infusion reactions, rash, esophagitis, cytokine release syndrome, and a number of infections. Even the selection of route of administration of antibiotics can change grades, as in wound infection, where if even a single dose of intravenous antibiotics is used, the grade increases from 2 to 3 over the use of topical or oral agents. ommon Terminology Criteria for Adverse Table C Events Grade and Clinical Severity1 Grade

Clinical severity

Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated

Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL

Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL

Life-threatening consequences; urgent intervention indicated

Death related to adverse event

ADL indicates activities of daily living.

www.JHOPonline.com

March 2015

Vol 5, No 1

EDITORIAL

In addition to adverse event reporting as part of clinical trials, the CTCAE may have effects on data interpretation, analysis, and translation to clinical use. Adverse events are often categorized into groups in manuscripts as “all” and “grade 3/4”; however, in many instances, clinically relevant grade 1 or 2 adverse events

Fine-tuning CTCAE interpretation and adverse event management may require new approaches, particularly for more subjective (eg, nonlaboratory value assessments) toxicities. have direct effects on premedications, supportive care, or other aspects of patient management. With the advent of improved antiemetic agents and regimens, the definition and significance of grade 1 and 2 vomiting take on a different level of importance. If a patient receiving cisplatin has 1 to 2 episodes of vomiting in a 24-hour period after treatment, we would clinically describe that as a failure of antiemetic therapy. However, per CTCAE

criteria, that is grade 1 vomiting. Similarly, grade 2 diarrhea is an increase of 4 to 6 stools daily over baseline, which, depending on other factors, most are likely to say is clinically relevant and requires intervention. Fine-tuning CTCAE interpretation and adverse event management may require new approaches, particularly for more subjective (eg, nonlaboratory value assessments) toxicities. One area of growing research is the use of patient-reported outcomes in clinical trials. Patients consistently report more and more severe adverse events than clinicians, but end points and definitions must be carefully selected in the context of supportive care and risk–benefit ratios of anticancer treatments.2 Until these approaches are fully developed, pharmacists and other clinicians should be aware of the real and potential effects of interventions and grading in clinical trials on patient management. n

References

1. US Department of Health & Human Services. Common Terminology Criteria for Adverse Events (CTCAE). http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_201006-14_QuickReference_5x7.pdf. Updated June 14, 2010. Accessed February 25, 2015. 2. Wilson MK, Collyar D, Chingos DT, et al. Outcomes and endpoints in clinical trials: bridging the divide. Lancet Oncol. 2015;16:e43-e52.

Request your subscription to Journal of Hematology Oncology Pharmacy

™

q Y ES! I would like to receive the Journal of Hematology Oncology Pharmacy q NO. Please discontinue my subscription.

™

as well as related educational supplements.

Signature (Required)

Specialty

Date (Required)

Address

Name

City/State/Zip

Company

E-mail

Title

Phone Please provide all information indicated, including date and signature. INCOMPLETE CARDS WILL NOT BE PROCESSED.

Fax to: 732.992.1881

Vol 5, No 1

March 2015

www.JHOPonline.com

Journal of Hematology Oncology Pharmacy

Original Research Original Research

Pharmacist-Run Vaccination and Medication Management Service for Patients After Bone Marrow Transplant Simon Pence, PharmD; Robert Mancini, PharmD, BCOP

J Hematol Oncol Pharm. 2015;5(1):8-11. www.JHOPonline.com Disclosures are at end of text

Background: To maintain immunity against vaccine-preventable disease, bone marrow transplant (BMT) patients need to receive vaccinations following transplantation. At St. Luke’s Mountain States Tumor Institute, this process historically involved little collaboration with the pharmacy, and led to extended wait times and, potentially, vaccination errors. In addition, BMT patients may be at a higher risk for medication-related errors because of their complex medical histories. Pharmacists are the ideal professionals to manage medication lists in BMT patients. Objectives: To determine the role of pharmacists in the vaccination process and medication management of patients after BMT. Methods: From January through April 2014, all BMT patients scheduled to receive vaccinations at St. Luke’s Mountain States Tumor Institute were seen by an immunization-certified pharmacist who assisted with the administration of vaccinations and performed a medication reconciliation/management session. Results: Twelve patients received vaccinations and were included in the pilot project and a total of 64 post-BMT vaccines were administered. Gross revenue from the pilot was approximately $7700. Changes to medication lists were made in 8 patients (67%) following pharmacist review. Conclusion: Pharmacist involvement in the post-BMT vaccination process improved overall patient care. They are the ideal healthcare professional to perform medication reconciliation, including the BMT patient population.

ith advances in technique and supportive care, bone marrow transplant (BMT) patients have a longer life expectancy now than when BMT was first performed more than 40 years ago. Despite much higher mortality rates than the general population, up to 80% of BMT patients who survive 5 years posttransplantation will be alive 20 years posttransplantation.1 However, patients who live longer can be at higher risk for complications, in part because of changes in their body’s immune system.2 One of these concerns is the loss of immunity that was previously achieved through vaccination. To regain immunity to vaccine-preventable diseases, including measles, mumps, hepatitis, and diphtheria, patients need to be revaccinated following BMT.3 In addition, BMT patients may require medications to treat chronic complications from their transplantation. It is well documented that medication discrepancies are common in many patients.4,5 BMT patients may be at a higher risk for medication discrepancies compared with the general population, because they are frequently

Dr Pence is Assistant Professor of Pharmacy Practice, Roseman University of Health Sciences, South Jordan, UT; Dr Mancini is Oncology Pharmacist, PGY2 Oncology Residency Director, St. Luke’s Mountain States Tumor Institute, Boise, ID.

Journal of Hematology Oncology Pharmacy

changing medications posttransplantation and have frequent transitions in their care between inpatient and outpatient settings.6 Pharmacists are the ideal healthcare professionals to provide medication reconciliation and management services.7,8 At St. Luke’s Mountain States Tumor Institute (MSTI) in Boise, ID, patients are asked to stay in the infusion area for approximately 30 minutes following vaccinations to monitor for adverse immunologic reactions from the vaccines. This is an ideal time for pharmacists to meet with patients and perform medication reconciliation or medication therapy management. The catalyst for this project at St. Luke’s MSTI was that, prior to its initiation, pharmacy had little involvement in the post-BMT vaccination process. This had led to prolonged wait times for patients, and could potentially lead to errors in administration, including the wrong vaccine or a vaccine being given at the incorrect time following transplant. Table 1 includes times when vaccinations should be given, from the current BMT protocol for autologous transplants. St. Luke’s MSTI is a regional cancer center that performs 15 to 25 autologous transplants annually and manages patients with postallogeneic transplantation. MSTI has 5 locations, 6 BMT physicians, and 2 nurse practitioners. BMTs are only

www.JHOPonline.com

March 2015

Vol 5, No 1

Pharmacist-Run Vaccination for Patients After BMT

performed at the Boise location but long-term follow-up can take place at any of the 5 practice sites. The pilot project was implemented to improve patient care by decreasing wait times and providing consistency throughout the post-BMT process. The project also attempted to determine if it could be cost-effective to have a pharmacist manage all BMT vaccines. To our knowledge, this is the first report addressing the role of a pharmacist in the posttransplant vaccination process.

Methods The purpose of this pilot project was to standardize the post-BMT vaccination process and to improve patient care by reducing wait times and avoiding potential vaccine or medication-related errors. The project was also designed to determine the feasibility of having a pharmacist available to manage vaccinations for postBMT patients. A pilot process improvement project was conducted from January through April 2014. We evaluated pharmacist involvement in the BMT vaccination process with concurrent medication therapy management for BMT patients. The pilot was conducted at St. Luke’s MSTI in Boise, ID, where >50% of BMT patients received their vaccinations. Because this was a pilot project, all patients who were receiving their post-BMT vaccines were included in the analysis. Data collected included patient demographics, vaccination costs, and changes made to medication lists following pharmacist interview. Data were collected at the time of patient interaction. All changes were updated in the patient’s electronic medical record, as well as on a data collection sheet used by the study investigators. To include all BMT patients in the pilot project, the primary investigator obtained a list of all BMT patients and determined when they would each be scheduled for their posttransplant vaccines, based on our institution’s vaccination policy (ie, 6, 12, and 24 months posttransplant for autologous transplants, varied based on outside institutions for allogeneic transplants; see Table 1). A pharmacist contacted the patient the day before his or her appointment to let them know that they would be assisting with the vaccination process, be available to review their medication list, and answer any questions they may have about their medications. The patient was encouraged to either bring their medications or an updated medication list to the appointment so that a medication reconciliation session could be completed. The day of the appointment, the pharmacist would ensure that the correct vaccines were ordered by their oncologist. The vaccines would then be entered into the pharmacy system so that they would be ready when the

Vol 5, No 1

March 2015

Current BMT Protocol at St. Luke’s MSTI for Table 1. Autologous Transplanta Immunization 6 Months 12 Months 24 Months DTaP

Diphtheria and tetanus

Hib conjugate

Pneumococcal 13 conjugateb

IPV

If at high risk

If first dose given

If second dose given

Hepatitis B MMR

Influenza (inactivated only)

Yearly during flu season; earliest dose 4 months posttransplant

Adapted from St. Luke’s MSTI’s Post-BMT Vaccination Protocol. The fourth pneumococcal vaccine may be given at 26 months with the polysaccharide vaccine. BMT indicates bone marrow transplant; DTaP, diphtheria and tetanus toxoids and acellular pertussis; Hib, Haemophilus influenzae type b; IPV, inactivated poliovirus; MMR; measles-mumps-rubella; MSTI, Mountain States Tumor Institute. a

patient showed up at the infusion center. An immunization-certified pharmacist assisted with the vaccination process by administering the vaccines in conjunction with the infusion center nurses. Following vaccination, medication reconciliation was performed with recommendations provided to the oncologist, and updates made to the patient’s chart.

Results During the pilot period, 21 patients were vaccinated across the 5 St. Luke’s MSTI sites. Eight patients were vaccinated outside of Boise, and 1 patient was an add-on vaccination and was not included in the pilot. The total number of patients included in the pilot was 12. The median age was 59 years (30-72 years), 67% (n = 8) of the patients were women, and the average number of medications per patient was 8.9. Overall, 7 patients had myeloma, 3 patients had non-Hodgkin lymphoma, and 2 patients had acute myeloid leukemia. Cost Considerations A total of 64 vaccines were administered during the pilot. The costs and list of the different vaccines administered are shown in Table 2. The total estimated gross revenue for 12 patients was approximately $7700. Because of variability in reimbursements among third-party payers, it is difficult to determine the actual revenue attributed to this pilot.

www.JHOPonline.com

Journal of Hematology Oncology Pharmacy

Original Research

Table 2 Cost and Charges for Vaccines Administered During the Pilot Cost, $

Charge, $a

Vaccines, N

Administration fee, $

Gross total, $

DTaP

39.50

61.37

207.49

Diphtheria and tetanus

20.93

92.85

815.33

130.48

354.45

3047.63

Hepatitis B

32.43

128.87

1517.32

Hib

25.28

72.02

920.88

IPV

32.43

75.37

875.32

MMR

53.94

158.57

269.26

9.13

14.00

69.74

Vaccine

Pneumococcal 13

Influenza Total

7722.97

Charges represent our billing price, which is chosen by our institution; however, this was not always reimbursed by the thirdparty payer so actual reimbursement may vary. DTaP indicates diphtheria and tetanus toxoids and acellular pertussis; Hib, Haemophilus influenzae type b; IPV, inactivated poliovirus; MMR; measles-mumps-rubella.

Medication Reconciliation Eight (67%) of the 12 patients had at least 1 change made to their medication list based on the pharmacist review. A total of 23 changes were made—12 medications added to medication lists, 10 medications removed or adjusted, and 1 therapeutic recommendation made to discontinue a proton pump inhibitor. In addition, pharmacists provided education on vaccines and prescription medications, recommendations related to over-thecounter and herbal products, and resources and education about the disposal of unneeded oral chemotherapy medications. Although not all of these services were used by all patients, a pharmacist was available to answer questions and facilitate discussions. Discussion Having a pharmacist available to oversee the postBMT vaccination process ensured that the vaccinations and staff were prepared in anticipation of a patient’s arrival. Although no objective data were obtained regarding patient wait times before and after the pilot, feedback from both nursing and pharmacy staff indicated that the vaccination process was smoother and more efficient following the initiation of the project. Based on our findings, the gross revenue from this pharmacist-involved vaccine service would be approximately $35,000 annually, which is far below the average pharmacist salary.9 This figure only represents the costs and charges for the vaccines and administration extrapolated from the 4-month pilot. Costs associated with staff time, infusion center charges, and other costs were not considered. Despite this low annual revenue, these findings may be able to contribute to the funding for a

Journal of Hematology Oncology Pharmacy

full-time BMT pharmacist position at St. Luke’s MSTI in the future. One aspect that was not specifically addressed in this pilot was how to manage the vaccines at the other St. Luke’s MSTI sites. A total of 8 patients were vaccinated at the other 4 St. Luke’s MSTI locations. A problem sometimes faced by other St. Luke’s MSTI sites is that each site must purchase an entire box of each vaccine in order to vaccinate a patient. The site may end up using only 1 to 3 vaccines before expiration, then disposing of the remainder—leading to increased cost because of waste. This could be an area of future focus and possible cost-savings. In addition to the information obtained from the vaccination pilot, it was discovered that 67% of the BMT patients potentially have medication errors on their medication lists. This is a small subset of the patient load at St. Luke’s MSTI, but other sources have suggested similar problems in patients with cancer in general.10 The medication reconciliation service could potentially be expanded to all patients at St. Luke’s MSTI regardless of cancer type or procedure because of the potential for decreasing medication-related errors.

Conclusion This pilot showed that by having a pharmacist involved in the post-BMT vaccination process, patients were able to receive better overall care, and demonstrated an additional area in which pharmacists can contribute to the healthcare team. The standardization of the vaccination process helped to decrease potential errors caused by inconsistencies. The medication reconciliation service identified that several of our patients had medication discrepancies, which we were able to correct.

www.JHOPonline.com

March 2015

Vol 5, No 1

Pharmacist-Run Vaccination for Patients After BMT

These discrepancies were identified by pharmacists despite each patient having a medication reconciliation performed by a nurse or medical assistant at each visit. This further demonstrates the value of the pharmacist in the medication reconciliation/management process. Correcting these discrepancies could potentially reduce medication-related errors in the future. n Author Disclosure Statement Dr Mancini is on the Speaker’s Bureau of Millennium Pharmaceuticals. Dr Pence reported no conflicts of interest.

References

1. Martin PJ, Counts GW Jr, Appelbaum FR, et al. Life expectancy in patients surviving more than 5 years after hematopoietic cell transplantation. J Clin Oncol. 2010; 28:1011-1016. 2. Majhail NS, Rizzo JD, Lee SJ, et al. Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation. Biol Blood

Marrow Transplant. 2012;18:348-371. 3. Tomblyn M, Chiller T, Einsele H, et al. Guidelines for preventing infectious complications among hematopoietic cell transplant recipients: a global perspective. Bone Marrow Transplant. 2009;44:453-558. 4. Committee on Quality of Health Care in America; Institute of Medicine. To Err Is Human: Building a Safer Health System. 1st ed. Washington, DC: National Academies Press; 2000. 5. Knez L, Suskovic S, Rezonja R, et al. The need for medication reconciliation: a cross-sectional observational study in adult patients. Respir Med. 2011;105(suppl 1): S60-S66. 6. Ho L, Akada K, Messner H, et al. Pharmacist’s role in improving medication safety for patients in an allogeneic hematopoietic cell transplant ambulatory clinic. Can J Hosp Pharm. 2013;66:110-117. 7. Conklin JR, Togami JC, Burnett A, et al. Care transitions service: a pharmacy- driven program for medication reconciliation through the continuum of care. Am J Health Syst Pharm. 2014;71:802-810. 8. Pence S, Shipley J. Medication reconciliation in the ED: the Licking Memorial Hospital experience. Ohio Pharmacist. 2012 May:18-19. 9. US Department of Labor. Occupational Outlook Handbook. Pharmacists. www. bls.gov/ooh/healthcare/pharmacists.htm. Published January 8, 2014. Accessed February 12, 2015. 10. Mancini R. Implementing a standardized pharmacist assessment and evaluating the role of a pharmacist in a multidisciplinary supportive oncology clinic. J Support Oncol. 2012;10:99-106.

THE WESTIN SEATTLE • SEATTLE, WASHINGTON

http://pmo-live.com

Vol 5, No 1

March 2015

www.JHOPonline.com

Journal of Hematology Oncology Pharmacy

Symptom Management Overview

Symptom Management Overview Section Editor: Joseph Bubalo, PharmD, BCPS, BCOP

Submit Your

Symptom Management Update Readers are invited to submit brief updates with practice insights on the care of a specific symptom or a cluster of symptoms associated with a condition that is often seen in patients with cancer. The updates will be presented in the form of a “How I Treat” type of article. The goal of this section is to present a quick background to enhance providers’ understanding of the symptoms associated with a specific condition and their characteristic presentation(s) and etiology. The emphasis should be on a concise description of available treatments and current course of therapy.

What is Symptom Management Overview? Each review should provide a brief description of the symptom(s) associated with a common condition in oncology and its evidence-based management. Article Format • Length of article: 800-1200 words • Tables: 1-3 • Describe the symptom(s) • Etiology • Treatment options: dose(s), frequency, titration parameters • Course of therapy: time to effect/symptom resolution, expected effects, special or target populations for specific therapies, side effects and their management, as appropriate • References: minimum 5; maximum 15

How to submit

Submit a Word file of your article at

WWW.JHOPONLINE.COM 12

Journal of Hematology Oncology Pharmacy

www.JHOPonline.com

March 2015

Vol 5, No 1

Symptom Management Overview

This section provides a quick update of symptomatic conditions in oncology and their management. Readers are invited to submit brief updates following the guidelines provided on page 12.

Prevention and Treatment of CytarabineInduced Keratoconjunctivitis By Joseph Bubalo, PharmD, BCPS, BCOP Assistant Professor of Medicine, Division of Hematology and Medical Oncology, Oncology Clinical Pharmacy Specialist, Oregon Health and Science University Hospital, OHSU Hospital and Clinics, Portland, OR

Symptom Overview Corneal toxicity with high-dose cytarabine is a well- established risk of therapy.1 Routine prophylaxis with eye drops, usually topical corticosteroid drops, is an established part of high-dose cytarabine treatment protocols.2 Without

topical corticosteroid prophylaxis, incidences of keratoconjunctivitis have been reported in 85% to 100% of cases3,4; the occurrence of clinically significant symptoms with the use of prophylaxis is reported in 8% to 16% of cases.3

Etiology Cytarabine has a known ability to penetrate body fluids, including crossing the blood–brain barrier, and can be found in the aqueous humor and in tears.5 Corneal toxicity appears to be related to the concentration of cytarabine in tears, and the duration of exposure. Risk factors vary with high-dose cytarabine (Table 1), and duration of dosing is most strongly associated with the toxicity4-6; few cases have been seen with intermittent or continuously administered intravenous, low-dose cytarabine (eg, <200 mg/m2/day).5 Conjunctivitis has occurred as early as 3 days into therapy, and several days after therapy, with days 6 to 8 posttherapy the most commonly reported time of occurrence.6-8 Findings at eye examinations have been described as bilateral corneal epithelial microcysts—possibly more densely distributed in the center of the cornea than in the midperiphery,5 conjunctival hyperemia, and fine corneal opacities.9 There is often severe blepharospasm and moderate conjunctival inflammation—however, the anterior chambers of the eyes are usually free of inflammation, and intraocular pressure is normal.5 The

isk Factors for Cytarabine-Induced Table 1 R Keratoconjunctivitis4-6 • C oncurrent total body irradiation with high-dose

cytarabine

• Cytarabine dose >1000 mg/m2; cases reported as low as

400 mg/m2 daily

• D uration of exposure variable with >5 days of high dose

or >10 days at more moderate doses (400-500 mg/m2); very rare at <2 days

mechanism of microcyst formation is currently unknown. Corneal epithelial stem cells have a long cycle time and are unlikely to be cytarabine-susceptible; however, they bring about more differentiated transient amplifying cells in the basal layer, which divide more frequently and may therefore be vulnerable to cytarabine toxicity. Common ocular symptoms include blurred vision, severe discomfort or burning pain, photophobia,3,5,7 decreased visual acuity, tearing,3,7 and foreign body sensation.3

TREATMENT OPTIONS Prophylaxis is generally not recommended at doses <1000 mg/m2.5 Suggested prophylaxis is corticosteroid eye drops5,6,8; however, other agents and combinations have been used successfully.8 These include a variety of preparations, including tear replacement solutions and Vol 5, No 1

March 2015

topical, nonsteroidal anti-inflammatory drops.6,8 Every 4- or 6-hour administration on a strict schedule appears to provide the most benefit, and drops should be continued at least 48 hours after the last cytarabine dose.6 The mechanism of conjunctivitis prevention is unclear, but

www.JHOPonline.com

Journal of Hematology Oncology Pharmacy

Symptom Management Overview

may rely on a decreased replication rate induced by corticosteroids impacting DNA replication in corneal cells.5 An additional mechanism of action may be a diluting effect on the cytarabine concentration; 1 trial showed benefits achieved from frequent use of artificial tears.6 It is unclear whether components of eye solutions, especially preservatives, can exacerbate the conjunctivitis. Given the limited studies on this toxicity, preservative-free products would be preferred when available.10 When conjunctivitis occurs there is no standard therapy, and treatment is often left to the local ophthalmologists, who generally apply additional corticosteroid eye drops, with other agents added in as needed.5 See Table 2

for a list of prophylaxes and Table 3 for treatments for cytarabine-induced conjunctivitis. Dexamethasone eye drops are the most common agent used to treat conjunctivitis, and there may be additional benefits derived by adding a topical nonsteroidal anti-inflammatory drug (NSAID).8 Dexamethasone has greater anti-inflammatory activity, and may have better corneal penetration than prednisolone. Pain, irritation, and other symptoms generally respond within days, with visual acuity returning to baseline by 2 weeks, and corneal opacities resolved by 4 weeks.3 Additional symptom benefits may be obtained through the application of cold compresses to the eye, and by keeping lights at a low level.6

Table 2 Prophylaxes for Cytarabine-Induced Conjunctivitis Agent Dose Duration

Comments

Betamethasone sodium phosphate 0.1% with natural tears or 0.1% sodium hyaluronate4

1 drop of each every 6 hours

Drops start 1 day prior to cytarabine and continue until 1 day after the last dose, or until complete resolution of any ocular symptoms

Used in HSCT regimens as described below. This regimen is associated with 66% grade 2-3 keratoconjunctivitis

Betamethasone sodium phosphate 0.1% with sterile saline eye rinse10

1 drop every 6 hours; rinse each eye with 3-4 mL of sterile saline in a commercial eye rinse cup

Drops start 1 day prior to cytarabine and continue until 1 day after, or until complete resolution of any ocular symptoms. Use sterile saline rinse every 10-15 minutes during cytarabine infusion and for 2 hours after the last dose (4 hours total)

Used as part of an HSCT conditioning regimen of TBI of 12 Gy following 4 days of cytarabine 3 g/m2 every 12 hours. This regimen is associated with 17% grade 2-3 keratoconjunctivitis. No adverse effects were attributed to the saline rinse

Dexamethasone 0.1%8

2 drops in each eye every 6 hours

Drops start 1 day prior to cytarabine and are continued for 4 days after the last dose

This regimen is associated with 92% grade 2-3 conjunctivitis. May be preferred over prednisolone because of higher anti-inflammatory activity

Dexamethasone 0.1% with diclofenac sodium 0.1%8

2 drops of dexamethasone Drops start 1 day prior to in each eye every 6 hours, cytarabine and continue for and 2 drops of diclofenac in 4 days after the last dose each eye every 8 hours

This regimen is associated with 25% grade 2-3 conjunctivitis

Artificial tears6

2 drops in each eye every 4 hours

Drops start 1 day prior to cytarabine, and continue for 48 hours after the last dose

Possibly equal to prednisolone in efficacy when given on a rigorous administration schedule every 4 hours

Natural tears2

2 drops in each eye every 8 hours

Drops start 1 day prior to cytarabine, and continue for 48 hours after the last dose

Inferior to prednisolone in efficacy when given on the same schedule

Prednisolone phosphate 1%2,6

Doses ranging from 2 drops Drops start 1 day prior to in each eye every 8 hours to cytarabine, and continue for 2 drops in each eye every 48 hours after the last dose 4 hours

More effective than a natural tear control administered every 8 hours in the opposite eye, but possibly equal to them when given on a rigorous administration schedule every 4 hours

HSCT indicates hematopoietic stem-cell transplantation; TBI, total body irradiation.

Journal of Hematology Oncology Pharmacy

www.JHOPonline.com

March 2015

Vol 5, No 1

Symptom Management Overview

Table 3 Treatments for Cytarabine-Induced Conjunctivitis Agent Dose Duration

Comments

Dexamethasone 0.1%5,6

1-2 drops every 2 hours

Drops continue until microcysts resolve, then become tapered over 1 week

Diclofenac sodium 0.1%8

2 drops in each eye every 8 hours

Combined with dexamethasone Symptoms resolved “promptly” (actual eye drops until symptoms time not defined) when diclofenac resolved was added to dexamethasone drops

Although it has been well-documented for >30 years, cytarabine-induced keratoconjunctivitis continues to be a poorly studied and problematic adverse effect of cytarabine use. Even though evidence has been reported that deoxycytidine, a competitive inhibitor of cytarabine, may be an effective antidote, a commercially available product for patient use is still not available.11 Unless a deoxycytidine product is developed and proven successful, the information currently available would support the addition of an NSAID eye drop to corticosteroids for high-risk or symptomatic patients.8 Additional research is clearly warranted in this area. n

References

1. Hopen G, Mondino BJ, Johnson BL, et al. Corneal toxicity with systemic cytarabine. Am J Ophthalmol. 1981;91:500-504.

Taper during 1 week as tolerated

2. Lass JH, Lazarus HM, Reed MD, et al. Topical corticosteroid therapy for corneal toxicity from systemically administered cytarabine. Am J Ophthalmol. 1982;94:617-621. 3. al-Tweigeri T, Nabholtz JM, Mackey JR. Ocular toxicity and cancer chemotherapy. A review. Cancer. 1996;78:1359-1373. 4. Mori T, Watanabe M, Kurotori-Sotome T, et al. Reduced efficacy of topical corticosteroid in preventing cytarabine-induced kerato-conjunctivitis in patients receiving high-dose cytarabine and total body irradiation for allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2008;42:197-199. 5. Lochhead J, Salmon JF, Bron AJ. Cytarabine-induced corneal toxicity. Eye (Lond). 2003;17:677-678. 6. Higa GM, Gockerman JP, Hunt AL, et al. The use of prophylactic eye drops during high-dose cytosine arabinoside therapy. Cancer. 1991;68:1691-1693. 7. Ritch PS, Hansen RM, Heuer DK. Ocular toxicity from high-dose cytosine ara binoside. Cancer. 1983;51:430-432. 8. Matteucci P, Carlo-Stella C, Di Nicola M, et al. Topical prophylaxis of conjunctivitis induced by high-dose cytosine arabinoside. Haematologica. 2006;91:255-257. 9. Stentoft J. The toxicity of cytarabine. Drug Safety. 1990;5:7-27. 10. Mori T, Kato J, Yamane A, et al. Prevention of cytarabine-induced kerato-conjunctivitis by eye rinse in patients receiving high-dose cytarabine and total body irradiation as a conditioning for hematopoietic stem cell transplantation. Int J Hematol. 2011;94:261-265. 11. Gococo KO, Lazarus HM, Lass JH. The use of prophylactic eye drops during high dose cytosine arabinoside therapy. Cancer. 1992;69:2866-2867.

VISIT OUR RECENTLY ENHANCED USER-FRIENDLY WEBSITE Read the most recent articles just published in the Journal of Hematology Oncology Pharmacy, the nation’s first peer-reviewed clinical journal for oncology pharmacists Review key studies recently published relevant to hematology/ oncology pharmacists Submit an article to the journal

www.JHOPonline.com Vol 5, No 1

March 2015

www.JHOPonline.com

Journal of Hematology Oncology Pharmacy

Oncology Providers Practice and Personalized Medicine Trends

Barbara L. McAneny, MD Chair, Board of Trustees American Medical Association

Sanjiv S. Agarwala, MD Professor of Medicine Temple University School of Medicine Chief, Medical Oncology & Hematology St. Luke’s Cancer Center

Omni Shoreham Hotel • Washington, DC TH

ANNUAL CONFERENCE

RSARY VE NI

AGENDA

MAY 5, 2015

7:00 am – 8:00 am

Meet the Experts Breakfast

8:00 am – 8:15 am

Introduction and Opening Remarks Barbara L. McAneny, MD, American Medical Association Sanjiv S. Agarwala, MD, Temple University School of Medicine

8:15 am – 9:15 am

Session 1 - Win-Win-Win Approaches to Oncology Care: How Providers, Patients, and Payers Can All Benefit from Improving the Way We Pay for Cancer Treatment Harold Miller, Center for Healthcare Quality and Payment Reform

1:15 pm – 2:00 pm

Session 6 - Keynote Session Value-Based Cancer Care: How Do We Get There in the ’Omics Era? Gary Palmer, MD, JD, MBA, MPH, Nanthealth

2:00 pm – 2:45 pm

Session 7 - Can We Afford Personalized Medicine? Michael Kolodziej, MD, Aetna

2:45 pm – 3:30 pm

Session 8 - The Precision Medicine Initiative: Deliverables from Those on the Front Lines of Personalizing Care Harold Varmus, MD, National Cancer Institute (Invited)

3:30 pm – 4:15 pm

Session 9 - Adapting Regulation to Meet the Needs of the Exponential Growth of the Molecular Testing Era Victoria Pratt, MD (Invited)

4:15 pm – 5:00 pm

Session 10 - Role of Pathologist in the Age of Personalized Medicine Pranil Chandra, DO, PathGroup (Invited)

5:00 pm – 5:45 pm

Session 11 - The Role of Immunotherapy in Personalizing Treatment James Allison, PhD, MD Anderson Cancer Center (Invited)

9:15 am – 10:00 am

Session 2 - Pitfalls or Challenges of New Payment Models Bruce Pyenson, Milliman

10:00 am – 10:15 am

Break

10:15 am – 11:00 am

Session 3 - Oncology Medical Home – A Patient-Centric System for Delivering Quality Cancer Care Barbara L. McAneny, MD, American Medical Association

11:00 am – 11:45 am

Session 4 - FDA on Testing and Personalized Medicine Speaker TBD

11:45 am – 12:15 pm

Session 5 - Revamping Research Raju Kucherlapati, PhD, Harvard Medical School

5:45 pm – 6:00 pm

Poster Award Q & A

12:15 pm – 1:15 pm

Networking Lunch in Exhibit Hall or Sponsored Lunch Presentation

6:00 pm – 6:15 pm

Closing Remarks

6:15 pm – 8:15 pm

Reception in Exhibit Hall

*Agenda subject to change.

AVBCC395_Agenda5Asize021215

AVBCConline.org/conference

Original Research

CLAG/CLAG-M in Patients with Relapsed/ Refractory Acute Myeloid Leukemia Christan M. Thomas, PharmD; Cindy Ippoliti, PharmD; Eric Feldman, MD Background: There is no standard salvage regimen for patients with relapsed/refractory acute myeloid leukemia (AML). Studies evaluating the efficacy of cladribine, cytarabine, and filgrastim with mitoxantrone (CLAG-M) or without mitoxantrone (CLAG) in the relapsed/refractory setting are also limited. Objective: The purpose of this study was to retrospectively evaluate the complete response (CR) rate of patients with AML treated with salvage regimen CLAG/CLAG-M. Methods: This study was a retrospective analysis of patients with relapsed/refractory AML who received treatment with CLAG or CLAG-M (cladribine 5 mg/m2 intravenously [IV] days 1-5, cytarabine 2 g/m2 IV days 1-5, and filgrastim 300 mcg subcutaneously days 1-5, with or without mitoxantrone 10 mg/m2 IV days 1-3) between January 2010 and December 2012. The primary end point was CR after completion of the CLAG or CLAG-M regimen. Thirty-five patients were included in the chart review. Results: Overall, 12 (34%) patients achieved CR with 1 of the study regimens. Additionally, 4 (11%) patients achieved with CR incomplete recovery, resulting in a combined CR and incomplete recovery rate of 46%. Conclusion: This review demonstrates CR rates similar to previously published CLAG/CLAG-M studies. CLAG/CLAG-M is an effective salvage regimen for patients with relapsed/refractory AML.

ecent statistics from the National Cancer Institute estimate that 25% of adults with acute myeloid leukemia (AML) are expected to survive for â&#x2030;Ľ3 years.1 Depending on other prognostic factors, such as duration of first remission, age, performance status, cytogenetics, and prior hematopoietic stem cell transplant, the overall survival of patients with relapsed/refractory disease at 5 years was <5%, and response rates were between 5% and 50%.1,2 Poor prognosis may be related to increasing age, cytogenetics and molecular mutations, and duration of first remission. Specifically, the absence of complete remission after the first induction therapy, and a remission duration of less than 6 months have been linked to worst patient outcomes.2 Although the National Comprehensive Cancer Network Guidelines for AML (version 1.2015) offer several options for the treatment of relapsed/refractory patients, no standard or preferred salvage regimen is available for this population.3 Regimens are typically chosen based on the discretion of the institution and the provider. Several

Dr Thomas is Assistant Clinical Professor at St Johnâ&#x20AC;&#x2122;s University College of Pharmacy, and Clinical Pharmacist at NewYorkPresbyterian Weill Cornell Medical Center, New York, NY; Dr Ippoliti is Clinical Pharmacy Manager at NewYork-Presbyterian Weill Cornell Medical Center, New York, NY; Dr Feldman is Professor of Medicine at NewYork-Presbyterian Weill Cornell Medical Center, New York, NY.

Vol 5, No 1

March 2015

J Hematol Oncol Pharm. 2015;5(1):17-20 www.JHOPonline.com Disclosures are at end of text

suggested regimens contain purine/pyrimidine analogues with or without an anthracycline.3 One regimen in the National Comprehensive Cancer Network Guidelines for AML includes cladribine, cytarabine, and filgrastim, with mitoxantrone (CLAG-M) or without mitoxantrone (CLAG).3 At this time, the medical literature offers few studies on the efficacy of the CLAG/CLAG-M regimen in patients with AML. To add to the body of literature describing this regimen in patients with relapsed/refractory AML, we conducted a retrospective analysis examining response rates in patients with AML after completion of CLAG/CLAG-M.

Methods This study was a retrospective analysis of patients with relapsed/refractory AML who received treatment with CLAG/CLAG-M: cladribine 5 mg/m2 intravenously (IV) days 1 to 5, cytarabine 2 g/m2 IV days 1 to 5, and filgrastim 300 mcg subcutaneously days 1 to 5, with or without mitoxantrone 10 mg/m2 IV days 1 to 3. Cladribine was infused over 2 hours, followed by a 4-hour infusion of cytarabine. Mitoxantrone was prepared in a small volume intravenously and administered during the course of 10 minutes. Patients could have received the regimen at any point during their salvage therapy, from the time of their first relapse to subsequent salvage therapy. The primary end point of interest was complete response (CR) after com-

www.JHOPonline.com

Journal of Hematology Oncology Pharmacy

Original Research

pletion of the CLAG or CLAG-M regimen. Secondary end points included with CR incomplete recovery (CRi), overall response (CR + CRi), duration of remission, overall survival, adverse effects, and number of patients who transitioned to hematopoietic stem cell transplantation. For the purpose of this study, CR was defined as bone marrow blasts <5%, absolute neutrophil count >1.0 × 109/L (1000/µL), and platelet count >100 × 109/L (100,000/µL) after bone marrow recovery. CRi was defined as meeting all CR criteria except for residual neutropenia or thrombocytopenia. Refractory patients were defined as not achieving CR after their first induction therapy. Relapsed patients were defined as having disease recurrence after previously achieving CR. Patients were eligible for inclusion if they were ≥18 years of age, diagnosed with relapsed or refractory AML, and treated with CLAG/CLAG-M regimens at New York-Presbyterian/Weill Cornell Medical Center (NYPWC) between January 2010 and December 2012. Patients Table 1 Baseline Characteristics Characteristics Male Median age at diagnosis, yrs (IQR)

Patients, N (%) (N = 35) 17 (49) 61 (56-70)

Previous HSCT

8 (23)

Risk statusa Better Intermediate Poor Unknown

6 (17) 8 (23) 19 (54) 2 (6)

Initial induction therapy 7 + 3 (cytarabine + idarubicin or daunorubicin) Decitabine Other/unknown

22 (63) 10 (29) 3 (9)

Duration of first CR Refractory <6 months 6-12 months >12 months Unknown

6 (17) 14 (40) 10 (29) 3 (9) 2 (6)

CLAG/CLAG-M therapy First salvage Second salvage >Second salvage

14 (40) 13 (37) 8 (23)

Based on baseline cytogenetics and molecular abnormalities. CLAG/CLAG-M indicates cladribine 5 mg/m2 intravenously (IV) days 1-5, cytarabine 2 g/m2 IV days 1-5, and filgrastim 300 mcg subcutaneously days 1-5, with or without mitoxantrone 10 mg/m2 IV days 1-3; CR, complete response; HSCT, hematopoietic stem cell transplantation; IQR, interquartile range. a

Journal of Hematology Oncology Pharmacy

Table 2 Results by Treatment Regimen CLAG-M, CLAG, Mini-CLAG, All patients N (%) N (%) N (%) (%) (n = 20) (n = 13) (n = 2) (N = 35) CR

8 (40)

4 (31)

0 (0)

12 (34)

CRi

4 (20)

0 (0)

4 (11)

Overall responsea

12 (60)

4 (31)

0 (0)

16 (46)

HSCT

7 (35)

2 (15.4)

0 (0)

9 (26)

CR + CRi. CLAG/CLAG-M indicates cladribine 5 mg/m2 intravenously (IV)days 1-5, cytarabine 2 g/m2 IV days 1-5, and filgrastim 300 mcg subcutaneously days 1-5, with or without mitoxantrone 10 mg/m2 IV days 1-3; CR, complete response; CRi, complete response with incomplete recovery; HSCT, hematopoietic stem cell transplantation. a

who did not receive these regimens or who had a diagnosis other than AML were excluded from the review. Variables collected during the analysis were age, sex, risk status for AML based on baseline cytogenetics, and molecular abnormalities as defined by National Comprehensive Cancer Network Guidelines, round of therapy (eg, first, second, or subsequent salvage therapy), first induction regimen, and duration of first CR. The retrospective analysis was approved by the NYP-WC Institutional Review Board.

Results Overall, the review included 35 patients with relapsed/refractory AML. Eight patients previously underwent hematopoietic stem cell transplantation. The majority of patients in this study received CLAG or CLAG-M as either first or second salvage therapy. In addition, 8 (23%) patients received therapy subsequently after the second salvage. Table 1 includes the baseline characteristics for the study population. Of the 35 patients included in the review, 20 (57%) received treatment with CLAG-M, 13 (37%) received CLAG, and 2 (6%) received a shortened, 3-day version of CLAG (“mini-CLAG” for the purpose of this study). Table 2 includes results by treatment regimen. In total, 12 (34%) patients achieved CR, 4 (11%) patients achieved CRi, and 16 (46%) patients achieved CR + CRi. When analyzed by regimen variation, response rates were greater in patients treated with CLAG-M compared with patients treated with CLAG or miniCLAG. Eight (40%) patients in the CLAG-M group achieved CR and 4 (20%) patients achieved CRi. Overall response in the CLAG-M group was 60%, compared with 4 (31%) patients who achieved CR or

www.JHOPonline.com

March 2015

Vol 5, No 1

CLAG/CLAG-M in Relapsed/Refractory AML

CRi with CLAG, and 0 patients with CR or CRi in the mini-CLAG cohort. Response rates by level of salvage therapy appear in Table 3. Overall, 4 (29%) of 14 patients who received CLAG or CLAG-M as a first salvage therapy regimen achieved CR. Five (38%) of 13 patients who received these regimens as second salvage therapy achieved CR. Three (38%) of 8 patients achieved CR during a third or later salvage therapy with CLAG or CLAG-M. Although this information was collected as part of the baseline characteristics, initial cytogenetics, initial white cell count, and first induction therapy regimen did not affect response rates in this review. Of the 8 patients who had previously received hematopoietic stem cell transplantation, 3 (38%) achieved CR or CRi. After treatment, 9 (56%) of 16 patients achieving a response were able to proceed to hematopoietic stem cell transplantation. For the 7 patients not proceeding to hematopoietic stem cell transplantation, the median duration of CR was 4 months (range, 1-7 months). Survival data were available for 34 of 35 patients. Median overall survival was 6 months (range, 0-39 months). One patient who received CLAG-M and proceeded to hematopoietic stem cell transplantation is still alive and in remission 39 months posttreatment. Overall, the regimen was well-tolerated (Table 4). All 35 (100%) patients reported hematologic toxicities, including neutropenia and thrombocytopenia. Four (11%) patients reported diarrhea, of which 3 (9%) cases were a result of the Clostridium difficile infection. Two (6%) patients had side effects affecting the central nervous system, including tremors and encephalopathy. In addition, 2 (6%) patients reported a rash during treatment. Incidence of grade 3 or 4 adverse events was low (Table 5). Two patients died during treatment before receiving the full therapy course; however, these were determined to be unrelated to therapy.

Discussion This retrospective study examined CR rates in patients with relapsed/refractory AML after CLAG/ CLAG-M therapy. Although there is no standard salvage regimen for relapsed/refractory AML, several agent combinations have been studied. Many of these regimens contain a combination of agents including a purine analogue, such as cladribine, fludarabine phosphate, or clofarabine. CR rates with CLAG or CLAG-M range between 30% and 60%.4-7 Another regimen comprising a purine analogue, a pyrimidine analogue, and a human granulocyte colony- stimulating factor, with or without an anthracycline, is FLAG-Ida—fludarabine phosphate, cytarabine, and filgrastim, with or without idarubicin. This regimen has

Vol 5, No 1

March 2015

Table 3 Results by Level of Salvage Therapy First, N (%) (n = 14)

Second, N (%) (n = 13)

Third or later, N (%) (n = 8)

4 (29)

5 (38)

3 (38)

CRi

2 (14)

1 (8)

1 (13)

Overall responsea

6 (43)

6 (46)

4 (50)

HSCT

3 (21)

4 (31)

2 (25)

CR + CRi. CR indicates complete response; CRi, complete response with incomplete recovery; HSCT, hematopoietic stem cell transplantation.

Table 4 Adverse Effects Patients, N (%) (N = 35) Neutropenia

35 (100)

Thrombocytopenia

35 (100)

Neutropenic fever

16 (46)

Diarrhea

4 (11)

Central nervous system toxicity

2 (6)

Increased bilirubin

2 (6)

Table 5 Grade 3 and 4 Adverse Effectsa (N = 35) Grade 3, Grade 4, Total, N (%) N (%) N (%) Increased bilirubin

1 (3)

2 (6)

Neutropenic fever

16 (46)

0 (0)

16 (46)

Based on Common Terminology Criteria for Adverse Events v4.0.

been extensively studied in relapsed/refractory AML. For FLAG and FLAG-Ida, CR rates have ranged between 30% and 80%, with most studies reporting a CR rate of approximately 50%.8-12 A third purine analogue, clofarabine, has also been studied in combination therapy for relapsed AML, with similar CR rates.13 Robak and colleagues conducted a phase 2, prospective, noncomparator trial of CLAG in patients with relapsed/refractory AML.4 This trial included 20 patients, 10 (50%) of whom were able to achieve CR with CLAG therapy.4 A second, retrospective study by Price and colleagues compared CLAG with another common salvage regimen—etoposide, cytarabine, and mitoxantrone hydrochloride (MEC).5 This study showed significantly higher response rates, overall survival, and relapse-free

www.JHOPonline.com

Journal of Hematology Oncology Pharmacy

Original Research

survival with CLAG compared with MEC. The authors reported that 45.5% of patients with primary refractory disease achieved CR with CLAG versus 22.2% with MEC. For patients in first relapse, 36.8% of patients achieved CR with CLAG versus 25.9% with MEC.5 Two studies from the Polish Adult Leukemia Group explored CLAG-M in patients with relapsed/refractory AML.6,7 A phase 2 study by Wrzesień-Kuś and colleagues in 2005 included 43 patients with relapsed or refractory AML who received induction treatment with CLAG-M.6 In this study, 49% of patients treated achieved CR.6 A second study by Wierzbowska and colleagues utilized the same study design and regimens used in the study by Wrzesień-Kuś and colleagues, but included 118 patients.7 Among these patients, 66 (58%) achieved CR after 1 or 2 induction cycles of CLAG-M.7 Another small, retrospective analysis examined 24 patients who received CLAG or CLAG-M.14 The authors reported a CR rate of 53% when the regimen was used as induction chemotherapy, and 44% when used as salvage treatment.14 Results of published studies are similar to those found in our retrospective study. Patients included in prospective trials, however, were allowed a second induction with the same regimen after achieving a partial response to the first cycle.5-7 This second induction may have also increased overall response rates, compared with patients in our retrospective study, where CR rates were only examined after 1 cycle of CLAG/CLAG-M. Our study has several limitations. In addition to being a single-center, noncomparative retrospective review, the selection of the study regimen lacked standard criteria. Although certain factors, including age, performance status, and comorbid conditions, may have played a role in deciding if a patient should receive mitoxantrone or a shortened treatment course, there were no set, institutional guidelines for this decision. Although this information was collected as part of the baseline characteristics, initial cytogenetics, initial white cell count, and first induction therapy regimen did not appear to affect response rates in this review. A formal, statistical analysis with stratification by risk status, however, was not performed. In addition, the retrospective nature of this review made accurate analysis of adverse effects challenging. The main toxicities of this regimen are hematologic in nature and include neutropenia and thrombocytopenia. In addition to response rates, several patients successfully transitioned to hematopoietic stem cell transplantation after CLAG/ CLAG-M therapy. Nine (56%) of 16 patients achieving a response were able to receive hematopoietic stem cell

Journal of Hematology Oncology Pharmacy

transplantation. The ability to transition to transplantation in this patient population is extremely important because allogeneic bone marrow transplantation generally results in the lowest incidence of relapse when compared with additional chemotherapy.

Conclusion This review demonstrates similar CR rates to previously published CLAG/CLAG-M studies. CLAG/ CLAG-M is an effective salvage regimen for relapsed/ refractory AML. n Author Disclosure Statement Dr Ippoliti is a Speaker for Sigma Tau and a Consultant for HealthHelp. Dr Thomas and Dr Feldman reported no conflicts of interest. No funding was provided for this study.

References

1. National Cancer Institute. Adult Acute Myeloid Leukemia Treatment (PDQ®). www.cancer.gov/cancertopics/pdq/treatment/adultAML/healthprofessional. Updated January 9, 2015. Accessed February 13, 2015. 2. Giles F, O’Brien S, Cortes J, et al. Outcome of patients with acute myelogenous leukemia after second salvage therapy. Cancer. 2005;104:547-554. 3. National Comprehensive Cancer Network. Acute myeloid leukemia. NCCN Guidelines. www.nccn.org/professionals/physician_gls/pdf/aml.pdf. Accessed January 23, 2015. 4. Robak T, Wrzesień-Kuś A, Lech-Marańda E, et al. Combination regimen of cladribine (2-chlorodeoxyadenosine), cytarabine and G-CSF (CLAG) as induction therapy for patients with relapsed or refractory acute myeloid leukemia. Leuk Lymphoma. 2000;39:121-129. 5. Price SL, Lancet JE, George TJ, et al. Salvage chemotherapy regimens for acute myeloid leukemia: is one better? Efficacy comparison between CLAG and MEC regimens. Leuk Res. 2011;35:301-304. 6. Wrzesień-Kuś A, Robak T, Wierzbowska A, et al. A multicenter, open, noncomparative, phase II study of the combination of cladribine (2-chlorodeoxyadenosine), cytarabine, granulocyte colony-stimulating factor and mitoxantrone as induction therapy in refractory acute myeloid leukemia: a report of the Polish Adult Leukemia Group. Ann Hematol. 2005;84:557-564. 7. Wierzbowska A, Robak T, Pluta A, et al. Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Eur J Haematol. 2008;80:115-126. 8. Steinmetz HT, Schulz A, Staib P, et al. Phase-II trial of idarubicin, fludarabine, cytosine arabinoside, and filgrastim (Ida-FLAG) for treatment of refractory, relapsed, and secondary AML. Ann Hematol. 1999;78:418-425. 9. Jackson G, Taylor P, Smith GM, et al. A multicenter, open, non-comparative phase II study of a combination of fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor in relapsed and refractory acute myeloid leukemia and de novo refractory anaemia with excess of blasts in transformation. Br J Haematol. 2001; 112:127-137. 10. de la Rubia J, Regadera AI, Martin G, et al. FLAG-Ida regimen (fludarabine, cytarabine, idarubicin and G-CSF) in the treatment of patients with high risk myeloid malignancies. Leuk Res. 2002;26:725-730. 11. Carella MA, Cascavilla M, Greco MM, et al. Treatment of poor risk acute myeloid leukemia with fludarabine, cytarabine and G-CSF (flag regimen): a single centre study. Leuk Lymphoma. 2001;40:295-303. 12. Huhmann IM, Watzke HH, Geissler K, et al. FLAG (fludarabine, cytosine arabinoside, G-CSF) for refractory and relapsed acute myeloid leukemia. Ann Hematol. 1996;73:265-271. 13. Scappini B, Gianfaldoni G, Caracciolo F, et al. Cytarabine and clofarabine after high-dose cytarabine in relapsed or refractory AML patients. Am J Hematol. 2012;87: 1047-1051. 14. Martin MG, Welch JS, Augustin K, et al. Cladribine in the treatment of acute myeloid leukemia: a single-institution experience. Clin Lymphoma Myeloma. 2009;9: 298-301.

www.JHOPonline.com

March 2015

Vol 5, No 1

FROM THE LITERATURE

Concise Reviews of Studies Relevant to Hematology Oncology Pharmacy With Commentaries by Robert J. Ignoffo, PharmD, FASHP, FCSHP Clinical Professor Emeritus, University of California, San Francisco; Professor of Pharmacy, College of Pharmacy, Touro University–California, Mare Island, Vallejo, CA nV emurafenib/Cobimetinib

Combination Improves Outcomes in Advanced Melanoma

BACKGROUND: Although the BRAF inhibitor vemurafenib (Zelboraf) improves progression-free survival (PFS) and overall survival (OS) in patients with advanced melanoma, 25% of patients using it as monotherapy end up with a second cancer. Combining BRAF and MEK inhibitors has been shown to prevent or delay the onset of resistance with BRAF inhibitors alone. A new study investigated the use of combining vemurafenib with the experimental MEK inhibitor cobimetinib. METHODS: This international, multicenter, randomized, phase 3 trial included 495 patients with untreated, unresectable locally advanced or metastatic BRAF V600 mutation melanoma. Patients were randomized in a 1:1 ratio to vemurafenib (960 mg twice daily) together with placebo (control group) or to cobimetinib (combination group; 60 mg once daily for 21 days, followed by 7 days off). The median follow-up at the time of reporting was 7.3 months. The primary end point was investigator- assessed PFS. The secondary end points were rates of confirmed objective response and OS. RESULTS: The median PFS was 9.9 months in the combination group compared with 6.2 months in the control group (hazard ratio for death or disease progression, 0.51; 95% confidence interval, 0.39-0.68; P <.001). The combination group had a significantly higher complete or partial response compared with the control group—68% versus 45%, respectively (P <.001); this included a complete response rate of 10% versus 4%, respectively. Interim OS analyses showed higher rates of survival at 9 months with the combination compared with control (81% vs 73%, respectively). Adverse events were reported in ≥20% of the patients in either group (eg, arthralgia, alopecia, diarrhea, and rash); however, combining vemurafenib with cobimetinib decreased the number of secondary cutaneous cancers. No significant difference was observed in grade ≥3 adverse events. Drug discontinuations were similar (13% and 12%, respectively). Approximately 50% of patients diagnosed with melanoma carry the BRAF mutation. Combination therapy with vemurafenib and cobimetinib demonstrated im-

Vol 5, No 1

March 2015

provement in PFS and response rate, reduced second cancers, and early evidence of improved OS among patients with BRAF V600 mutation metastatic melanoma, at the cost of some increase in toxicity. Source: Larkin J, Ascierto PA, Dréno B, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014;371:1867-1876. COMMENTARY BY ROBERT J. IGNOFFO

The phase 3 study by Larkin and colleagues is an important advance in the concept of combination MEK and BRAF inhibition for the treatment of patients with malignant melanoma. The combination of vemurafenib and cobimetinib led to improved PFS/OS at 9 months, and tumor responses while minimizing the risk of second cancers associated with squamous-cell carcinoma, a worrisome problem when patients are treated with the BRAF inhibitor, vemurafenib, alone. Although the combination produced more grade 3 adverse effects (nausea, vomiting, and diarrhea), none were life-threatening and most were grade 1 or 2, which can be easily managed with supportive care medications. These results appear to be similar to those from another phase 3 trial evaluating the combination of other MEK and BRAF inhibitors, dabrafenib and trametinib.1 A New Drug Application has been filed by Genentech and was accepted by the US Food and Drug Administration, which announced an action date of August 11, 2015, to review the combination for the treatment of patients with advanced melanoma. The landscape for treating patients with advanced melanoma has improved dramatically in the past few years with the discovery of new signaling pathways (BRAF, MEK, and MAP-kinase) that serve as therapeutic targets. Unfortunately, the monthly cost of a combination is likely to range between $16,000 and $20,000; vemurafenib alone has an average wholesale price of $11,200 per month.2 1. Robert C, Karaszewska B, Schachter J, et al. Improved overall survival in melanoma with combined dabrafenib and

www.JHOPonline.com

Journal of Hematology Oncology Pharmacy

FROM THE LITERATURE

trametinib. N Engl J Med. 2015;372:30-39. 2. Hawaii Medical Service Association. Zelboraf. www.hmsa. com/PORTAL/PROVIDER/MEDCO_Cancer_Agents_ Zelboraf_Summary_111611.pdf. Published November 2011. Accessed February 25, 2015.

nA ssessing

the Economic Impact of Targeted Therapies in Advanced NSCLC

BACKGROUND: Improved understanding of the biol ogy of non–small-cell lung cancer (NSCLC) has led to increasing stratification of treatment based on pathologic and molecular characteristics to obtain the greatest clinical benefit for patients while minimizing the adverse effects. However, these advances have come at a financial cost. METHODS: In a review article, the researchers examined the economic impact of screening for molecular abnormalities and new targeted treatments for advanced NSCLC. RESULTS: The researchers found that major determinants of cost are molecular testing and drug price. For a molecular targeted therapy, adequate tissue sampling and accuracy of testing method are important. International guidelines recommend routine immunohistochemistry (IHC) staining for NSCLC diagnosis, the use of histologic subtype and molecular testing to detect EGFR mutation, and EML4-ALK fusion for patients with advanced NSCLC. The amount of tissue required and the labor intensiveness depends on the biomarker screening technique used (eg, IHC or fluorescence in situ hybridization [FISH]). The researchers reviewed testing methods and cost across a range of studies. One study analyzed the cost- effectiveness of testing for using FISH and IHC. The data showed that FISH testing was assessed at $106,707 per quality-adjusted life-year (QALY) gained compared with $57,165 per QALY gained for IHC. A Canadian study explored the cost-effectiveness of 2 treatment approaches for patients with EML4-ALK fusion–positive tumors. One approach consisted of molecular screening (initial IHC and, if positive, confirmatory testing with FISH) and targeted treatment with crizotinib (Xalkori). Molecular testing led to an increase of 0.11 QALYs and a $2725 (Canadian dollars) increase in cost per patient. Fusion testing accounted for $60 of those costs. For patients who have confirmed EML4-ALK–positive tumors, first-line therapy with crizotinib resulted in an incremental cost-effectiveness ratio (ICER) of $250,632 per QALY gained, which is more than the frequently accepted cost-effectiveness thresholds. Drug cost is an underlying concern for patients and payers regarding targeted therapies. Studies of EGFR tyrosine kinase inhibitors (TKIs) in patients with EGFR- mutated advanced NSCLC have demonstrated im-

Journal of Hematology Oncology Pharmacy

proved response rate, quality of life, and PFS compared with chemotherapy. Given these clinical benefits, analyses have been performed to determine the cost-effectiveness of first-line EGFR TKI therapy. A British study that compared gefitinib (Iressa) with platinum-doublet chemotherapy calculated an estimated ICER of £59,216 to £70,390 per QALY for gefitinib; however, it was not considered cost-effective at standard willingness-to-pay thresholds. In a separate study, from the perspective of the Chinese healthcare system, researchers compared the cost-effectiveness of erlotinib (Tarceva) monotherapy and platinum-doublet chemotherapy in patients with advanced EGFR mutation NSCLC. Treatment with erlotinib was deemed cost-effective, with an ICER of $85,927.41 per QALY gained. The cost of lung cancer in the United States is predicted to be $15.19 billion by 2020, without accounting for changes in treatment and the FDA approval of novel agents. As technology advances, molecular testing costs may become lower. The advances in targeted therapies have dramatically changed the diagnosis and treatment of NSCLC for patients with a previously poor prognosis. Collaboration among clinicians, payers, and manufacturers is needed to ensure that treatment cost does not limit patient accessibility to potentially beneficial treatments. Source: Graham DM, Leighl NB. Economic impact of tissue testing and treatments of metastatic NSCLC in the era of personalized medicine. Front Oncol. 2014;4:258. COMMENTARY BY ROBERT J. IGNOFFO

Strategies for the treatment of patients with metastatic lung cancer have been transformed substantially with the advancement of molecular testing and the development of personalized medications that target receptors responsible for the growth of NSCLC. Although the study by Graham and colleagues was performed in Canada, the results are relevant to the management of NSCLC in the United States. Because the cost of molecular testing of tumors is likely to decrease as a result of increased future utilization, it appears that the cost of treating patient with advanced lung cancer will be associated primarily with the expensive targeted agents. If the cancer is curable, then cost is secondary. However, if the cancer is minimally curable, the cost to society will be at a great price, most notably for metastatic cancers involving malignant melanoma, renal-cell carcinoma, breast cancer, and colon cancer. I agree with the authors that efforts must be made to work with payers and drug companies to ensure that our patients have access to newly targeted agents, but at a reasonable cost to society.

www.JHOPonline.com

March 2015

Vol 5, No 1

Government and Employer Trends

Jayson Slotnik, JD, MPH Partner Health Policy Strategies, Inc

F. Randy Vogenberg, PhD, RPh Principal Institute for Integrated Healthcare (IIH)

Omni Shoreham Hotel • Washington, DC TH

ANNUAL CONFERENCE

RSARY VE NI

AGENDA

MAY 6, 2015

7:00 am – 8:00 am

Meet the Experts Breakfast

8:00 am – 8:15 am

Introduction and Opening Remarks Jayson Slotnik, JD, MPH, Health Policy Strategies, Inc F. Randy Vogenberg, PhD, RPh, Institute for Integrated Healthcare

8:15 am – 9:00 am

Session 1 - Oncology Bundled Payments Speaker TBD

9:00 am – 9:45 am

Session 2 - Media Coverage Oncology Panel Speaker TBD

9:45 am – 10:00 am

Break

10:00 am – 10:45 am

Session 3 - Actuary View and Future Market Landscape Speaker TBD

10:45 am – 11:30 am

Session 4 - Coverage Parameter Trends in Health Benefits Impacting Oncology Speaker TBD

11:30 am – 12:15 pm

12:15 pm – 1:15 pm

Networking Lunch in Exhibit Hall or Sponsored Lunch Presentation

1:15 pm – 2:00 pm

Session 6 - Private Health Exchanges Laurel Pickering, Northeast Business Group on Health

2:00 pm – 2:45 pm

Session 7 - Onsite and Retail Clinic Services Expansion Larry Boress, Midwest Business Group on Health

2:45 pm – 3:30 pm

Session 8 - Group Health Benefits 2016 and Beyond Brian Klepper, PhD, National Business Coalition on Health

3:30 pm – 4:15 pm

Session 9 - Panel Discussion: Patient Engagement Patrick McKercher, PhD, Patient Assistance Network Foundation

4:15 pm – 4:30 pm

Closing Remarks

*Agenda subject to change.

Session 5 - Keynote Session – 21st-Century Cures Speaker TBD

AVBCC395_Agenda6Asize021215

AVBCConline.org/conference

Cancer cell

Amgen is researching ways to help T cells target cancer.

Lyse

Oncolytic Immunotherapy is an innovative area of research that uses a modified virus designed to induce tumor cell lysis and expose tumor-derived antigens.

Learn

Activated dendritic cells can teach T cells to help find and fight cancer cells with a matching antigen profile.1

Explore whatâ&#x20AC;&#x2122;s new at:

OncolyticImmunotherapy.com

Dendritic cell