Welcome and Introduction
Teresa Miceli, RN, BSN, OCN IMF InfoLine Advisor, Nurse Leadership Board Member; Mayo ClinicRochester
Yelak Biru President and CEO
28 Year Myeloma Patient
2024 Minneapolis Patient and Family Seminar
July 19-20, 2024
THANK YOU TO OUR SPONSORS!
What do the dots mean?
More than 1 year since diagnosis
Stem cell transplant recipient
Less than 1 year diagnosed
Care Partner for someone with Myeloma
Saturday Agenda: Morning
7:00 – 8:00 AM Registration & Breakfast
8:00 – 8:10 AM Welcome & Announcements
Yelak Biru, CEO and 28-year Myeloma Patient
Teresa Miceli, RN BSN OCN
8:10 – 8:30 AM President & CEO Address
Yelak Biru
8:30 – 9:15 AM Keynote Lecture: What is the Future of Myeloma? w/ Q&A
Morie Gertz, MD, Mayo Clinic – Rochester, MN
9:15 – 9:30 AM Support Group Update
Becky Bosley, RN BSN - Director, Support Groups
9:30 – 9:45 AM BREAK
9:45 – 10:45 AM Breakout Session #1: Treatment Approaches in Myeloma, 30-minute lecture w/20-minute facilitated discussion
Breakout A: Newly Diagnosed: An Approach to Frontline Therapy
Jeff Zonder, MD, Karmanos Cancer Institute
Diamond Ballroom ABC
Breakout B: An Approach to Relapsed Myeloma
Jonathan Kaufman, MD, Winship Cancer Institute of Emory University
Diamond Ballroom E
10:45 – 10:50 AM RETURN TO MAIN SESSION
10:50 – 11:05 AM Partnering with the IMF
Sylvia Dsouza – Vice President, Development
Reminder: After Break, return to designated Break-Out Room
11:05 – 11:40 AM Symptom Management and Living Well with Myeloma
Beth Faiman, PhD, MSN, APN-BC, BMTCN, AOCN, FAAN, FAPO; Cleveland Clinic, IMF Nurse Leadership Board Member
11:40 AM – 12:00 PM Health Disparities in Myeloma,
Joseph Mikhael, MD, MEd, FRCPC, FACP
Saturday Agenda: Afternoon
12:00 – 1:00 PM LUNCH
Reminder: After Lunch, return to designated Break-Out Room
1:00 – 1:40 PM Breakout Session #2:
Patients and Care Partners
Breakout A: Patients Only – Lessons Learned
Yelak Biru, IMF President & CEO, 28-year Myeloma Patient
Diamond Ballroom E
Breakout B: Care Partners Only
Teresa Miceli, RN, BSN, OCN - InfoLine Advisor, Nurse Leadership Board; Mayo Clinic-Rochester
Ruby (2nd Floor)
1:40 – 1:45 PM RETURN TO GENERAL SESSION
1:45 – 2:15 PM Wild Card Topic: Practical Aspects of Immunotherapy
Rahma Warsame, MD, Mayo Clinic – Rochester, MN
2:15 – 2:55 PM Ask – the – Experts with Guest Faculty
2:55 – 3:00 PM Closing Remarks & Program Evaluation
Parking Reimbursement
Hotel Guests: Please put parking on your room, and the IMF will cover this directly with the hotel.
Meeting Attendees: Please See Lauren at the registration desk for a voucher.
EVALUATION
Please be sure to complete your program evaluation today.
Questions 1 – 5 can be completed before the program begins.
Questions 7 & 8 can be answered after each presentation.
If you are attending Friday program only, we ask that you turn the survey in at the end of the day.
If you are coming back for the Saturday sessions, please hold onto your survey, bring it back tomorrow and turn it in at the end of the program.
We greatly appreciate your time and feedback!
President & CEO Address
Yelak Biru President and CEO
What is the Future of Myeloma?
Morie Gertz, MD
Mayo Clinic – Rochester, MN
Support Group Update
Becky Bosley, RN BSN Director, Support Groups
International Myeloma Foundation
International Myeloma Foundation Support Group Team
Robin Tuohy Vice President, Patient Support
Nancy Bruno PT Director, Support Groups
Becky Bosley Director, Support Groups
Cecilia Romero Project & Technology Manager, Support Groups
Support Groups make a Difference!
Local Support Groups: You Are Not Alone!
Multiple Myeloma Sharing SessionsRochester
Meets virtually the 3rd Saturday of each month at 10am Central
The Twin Cities Multiple Myeloma Education & Networking Group
Meets in a hybrid fashion the 2nd Saturday of each month at 10am Central
The Stillwater Multiple Myeloma Support Group
The Central Minnesota Multiple Myeloma Support Group
Meets in-person the 2nd Saturday of each month at 10am Central
Meets in a hybrid fashion the 2nd Wednesday of each month at 1pm Central
The Eastern South Dakota Multiple Myeloma Support Group
Meets in-person the 2nd Tuesday of each month at 6pm Central
IMF – Special Interest Virtual Groups
Special interest groups are designed as a supplemental support for specific populations of patients, in addition to their local Support Groups
Las Voces de Mieloma-founded in 2022
Designed for Spanish speaking patients only
Living Solo & Strong with Myelomafounded in 2022
Designed for patients without a care partner
High Risk Multiple Myeloma-founded in 2023
Designed to address the needs of the high risk MM population
Care Partners Onlyfounded in 2024
Designed to address the needs and concerns of care partners
Link available here
Smolder Bolder-founded in 2023
Created for people living with Smoldering Multiple Myeloma
MM Families-founded in 2021
For patients/care partners with young children
IMF | Support Group | Resources
Monthly Support Group Newsletter
• Key Links and Resources
• Helps Leader with Agenda Planning
• Informs Group Members
• Increases IMF website engagement
Monthly Support Group Newsletter: Distribution
• US Leaders: 255
• Leaders Share to Group Mailing List: ~6,100
• IMF Staff & NLB Members
• Myeloma Canada for their Distribution
• Support Group Leader Toolkit
• Each Support Group’s Website
Links to register for upcoming webinars, workshops, & conferences
IMF | Support Group | Resources
SGLS 2023 Theme: Uniting Voices, Connecting Lives: Empowering Myeloma Communities Together
24th Annual Support Group Leaders Summit 2023
In-Person Program | October 5-8 | Houston, TX
Uniting Voices, Connecting Lives: Empowering Myeloma Communities Together
The goal of the program was to support leaders by increasing
• Knowledge
• Connections
• Sharing the Hope
Wellness Excursion to Houston Botanical Gardens a HUGE
Success Theme/Goals met: Engage, Empower, Educate = Increased Hope!
ASH – Dr. Joe’s & SG Leaders Facebook
IMF – Care Partner Resources
Self-Care for the Care Partner
Caring Through the Journey
Talking with Your Loved Ones
Managing the Cost of Care
BREAK
Reminder: After Break, return to designated Break-Out Room
Breakout Session #1: Treatment Approaches in Myeloma
30-minute lecture w/20-minute facilitated discussion
Breakout A: Newly Diagnosed: An Approach to Frontline Therapy
Jeff Zonder, MD, Karmanos Cancer Institute
Diamond Ballroom ABC
Breakout B: An Approach to Relapsed Myeloma
Jonathan Kaufman, MD, Winship Cancer Institute of Emory University
Diamond Ballroom E
Welcome Back
Breakout Sessions #1: Treatment Approaches in Myeloma
An Approach to Relapsed Myeloma
Jonathan Kaufman, MD,
Winship Cancer Institute of Emory University
Objectives
• Discuss an approach to treating relapsed myeloma based on patient, disease and treatment characteristics
• Review the important trend of using an aggressive approach in early treatment of myeloma
• Outline the key results from recent trials in early relapse
• Discuss the approach to late relapse and the use of novel therapies such as CAR T and bispecific antibodies
Early lines treatment are important!
1st Relapse 2nd 3rd 4th 5th and beyond
Fewer patient are eligible for therapy in each subsequent line of therapy (LOT)
Figure adapted from: Yong, K et al. Br J Haematol 2016;175(2):252-264
An Approach to Relapsed MM
• It is not a simple algorithm of treatment #1 then 2 then 3…
• Leverage the benefit of multiple mechanisms of action in combination therapy
Categories:
• 1-3 prior lines
• Later Relapse
• Refractory to PI, IMiD and MoAb = Triple Class Refractory
Principles
1. Depth of Response matters…likely incorporate MRD soon
2. High risk vs standard risk…more aggressive Rx in high risk
3. Balance efficacy and toxicity…initially and constantly assess
4. Overcome drug resistance…change mechanism of action when possible
Definitions: What is relapsed/refractory disease and a line of therapy?
• Relapsed: recurrence (reappearance of disease) after a response to therapy
• Refractory: progression despite ongoing therapy
• Progression: change in M protein/light chain values
• Line of therapy: change in treatment due to either progression of disease or unmanageable side effects
• Note: initial (or induction) therapy + stem cell transplant + consolidation/ maintenance therapy = 1 line of therapy
NCCN Guidelines – Early Relapse
NCCN Guidelines – Early Relapse contd.
Therapy Selection Considerations
Disease-Related
• Nature of the relapse
– Biochemical vs symptomatic
• Risk stratification
– High-risk chromosomal abnormalities: del(17p), t(4;14), t(14;16)
• Disease burden
Therapy-Related
• Previous therapies
• Prior treatmentrelated adverse event
• Regimen-related toxicity
• Depth and duration of previous response
• Cost to patient
Patient-Related
• Renal insufficiency
• Hepatic impairment
• Comorbidities
• Preferences
• Social factors
– Support system
– Accessibility to treatment center
– Insurance coverage
Multiple Myeloma is Not One Disease!
Myeloma: first relapse – IMWG Guidelines
First Relapse
Not Refractory to Lenalidomide
Refractory to Lenalidomide
Preferred options: DRd (or KRd)
Alternatives:
DVD, Kd, DaraKd, IsaKd, IRd, Erd
When Dara, Isa, K not available:
Rd, Vd, VTD, VCD, VMP
Preferred options: PVd DaraKd IsaKd
Consider salvage auto transplant in eligible patients
Second options
DaraVd;Kd
Other options:
KPd; DaraPd; Ipd
When Dara, isa, K or P not available: VCD, Vd, VMP
DKd,daratumumab/carfilzomib/dexamethasone; DPd, daratumumab/pomalidomide/dexamethasone; DRd, daratumumab/lenalidomide/ dexamethasone; DVd, daratumumab/bortezomib/dexamethasone; Elo–Rd, elotuzumab/lenalidomide/dexamethasone; Ipd, ixazomib/pomalidomide/dexamethasone; Ird, ixazomib/lenalidomide/dexamethasone; Isa–Kd, isatuximab/carfilzomib/dexamethasone; Kd, carfilzomib/dexamethasone; KPd, carfilzomib/pomalidomide/dexamethasone; KRd, carfilzomib/lenalidomide/ dexamethasone; PVd, pomalidomide/bortezomib/dexamethasone; Rd, lenalidomide/dexamethasone; SVd, selinexor/bortezomib/dexamethasone; VCd, bortezomib/cyclophosphamide/dexamethasone; Vd, bortezomib/dexamethasone; VMP, bortezomib/melphalan /prednisone; VTd, bortezomib/thalidomide/dexamethasone.
Moreau P, et al. IMWG Recommendations for RRMM. Lancet Oncol. 2021;22(3):e105-e118.
Early Relapse
General Principles
Use mechanisms of action not previously used
Do not continue to use lenalidomide if progressing on len maintenance
Triplets are preferred over doublets
In real practice - most patients receiving VRD (Bortezomib-Lenalidomide-Dex) like regimens, 1st relapse is typically
Daratumumab + Pomalidomide + Dex (APOLLO)
Isatuximab + Pomalidomide + Dex (ICARIA)
Daratumumab + Carfilzomib + Dex (CANDOR)
Isatuximab + Carfilzomib + Dex. (IKEMA)
Selinexor + Bortezomib + Dex (BOSTON)
First Relapse
Not Refractory to Lenalidomide* Refractory to Lenalidomide*
Not refractory to
CD38 moAB
Dara-refractory or Relapse while on CD38 moAB
Not refractory to CD38 moAB
Dara-refractory or Relapse while on CD38 moAB
DKd or Isa-Kd
Or DPd or Isa-Pd DRd
KRd (preferred) ERd, IRd (Alternatives) KCd or KPd (preferred) VCd or
(Alternatives)
*Consider salvage ASCT in patients eligible for ASCT who have not had transplant before; Consider
2nd auto SCT if eligible and had >36 months response duration with maintenance to first ASCT
Currently Available Agents for One to Three Prior Lines of Therapy
Drug Formulation Approval
Velcade (bortezomib)
Kyprolis (carfilzomib)
Ninlaro (ixazomib)
Revlimid (lenalidomide)*
Pomalyst (pomalidomide)*
XPOVIO (selinexor)
• IV infusion
• SC injection
• IV infusion
• Weekly dosing
• For relapsed/refractory myeloma
• For relapsed/refractory myeloma as a single agent, as a doublet with dexamethasone, and as a triplet with Revlimid or Darzalex plus dexamethasone
Once-weekly pill
Once-daily pill
• For relapsed/refractory myeloma as a triplet with Revlimid and dexamethasone
• For relapsed/refractory myeloma in combination with dexamethasone
Once-daily pill
• For relapsed/refractory myeloma in combination with dexamethasone
Once-weekly pill
• For relapsed/refractory myeloma as a triplet with Velcade and dexamethasone
*Black box warnings: embryo-fetal toxicity; hematologic toxicity (Revlimid); venous and arterial thromboembolism
Proteasome Inhibitor–
and Immunomodulatory Drug–Based Regimens for Early Relapse
OPTIMISMM
• Velcade-Pomalystdex (VPd) vs Vd Regimens compared
ASPIRE TOURMALINE-MM1 BOSTON
• Kyprolis-Revlimiddex (KRd) vs Rd
Median progression-free survival favored
• VPd: 11 vs 7 months
• KRd: 26 vs 17 months
• Ninlaro-Rd (IRd) vs Rd
• Consider for relapse on Revlimid
• VPd associated with more low blood counts, infections, and neuropathy than Pd Clinical considerations
• KRd associated with more upper respiratory infections and high blood pressure than Rd
• IRd: 21 vs 15 months
• XPOVIO-Velcadedex (XPO-Vd) vs Vd
• XPO-Vd: 14 vs 9 months
• IRd an oral regimen
• Gastrointestinal toxicities and rashes
• Lower incidence of peripheral neuropathy
• XPO-Vd associated with low platelet counts and fatigue with triplet, but less neuropathy than the Vd
Currently Available Naked Monoclonal Antibodies
for One to Three Prior Lines of Therapy Drug
Darzalex (daratumumab)
SC once a week for first 8 weeks, then every 2 weeks for 4 months, then monthly
• For relapsed/refractory myeloma as a single agent and as a triplet with Revlimid or Velcade or Kyprolis or Pomalyst plus dexamethasone
Empliciti (elotuzumab)
Sarclisa (isatuximab)
IV once a week for first 8 weeks, then every 2 weeks (or every 4 weeks with pom)
IV once a week for first 4 weeks, then every 2 weeks
• For relapsed/refractory myeloma as a triplet with Revlimid or Pomalyst and dexamethasone
• For relapsed/refractory myeloma as a triplet with Pomalyst or Kyprolis and dexamethasone
Monoclonal Antibody–Based Regimens
for Early Relapse: Darzalex
POLLUX
• Darzalex-Revlimiddex (DRd) vs Rd Regimens compared
CASTOR CANDOR APOLLO
• Darzalex-Velcadedex (DVd) vs Vd
• Darzalex-Kyprolisdex (DKd) vs Kd
• Darzalex-Pomalystdex (DPd) vs Pd
• DRd: 45 vs 18 months Median progressionfree survival favored
• DVd: 17 vs 7 months
• DKd: 29 vs 15 months
• DPd: 12 vs 7 months
• Consider for relapses from Revlimid or Velcade maintenance
• DRd associated with more upper respiratory infections, low blood white blood cell counts, and diarrhea Clinical considerations
• Consider for patients who are Revlimid-refractory without significant neuropathy
• DVd associated with more low blood cell counts
• Consider for younger, fit patients who are doublerefractory to Revlimid and Velcade
• DKd associated with more respiratory infections
• Sever side effects (possibly fatal) in intermediate fit patients 65 and older
• Consider in patients who are double-refractory to Revlimid and a proteasome inhibitor (Velcade, Kyprolis, Ninlaro)
• Severe low white blood cell counts
Monoclonal Antibody–Based Regimens
for Early Relapse: Sarclisa and Empliciti
ELOQUENT-2
• Empliciti-Revlimiddex vs Rd Regimens compared
ELOQUENT-3 ICARIA-MM IKEMA
• EmplicitiPomalyst-dex vs Pd
• Empliciti-Rd: 19 vs 15 months Median progressionfree survival favored
• Empliciti-Pd: 10 vs 5 mos
• Sarclisa-Pomalyst-dex vs Pd
• Sarclisa-Pd: 12 vs 7 mos
• Sarclisa-Kyprolis-dex vs Kd
• Sarclisa-Kd: 41 vs 19 mos
• Consider for nonRevlimid refractory, frailer patients
• Overall survival benefit with Empliciti-Rd
• Empliciti-Rd associated with more infections Clinical considerations
• Consider for patients refractory to Revlimid and a proteasome inhibitor (Velcade, Kyprolis, Ninlaro)
• Consider for patients refractory to Revlimid and a proteasome inhibitor (Velcade, Kyprolis, Ninlaro)
• Sarclisa-Pd associated with severe low white blood cell counts, more dose reductions, upper respiratory infections, and diarrhea
• Consider for patients refractory to Revlimid and Velcade
• Sarclisa-Kd associated with higher MRD negativity rates
• Sarclisa-Kd associated with severe respiratory infections
Myeloma: Second or
Refractory to IMiD, PI, Anti-CD38
Second or higher relapse
Refractory to IMiD, PI, Anti-CD38, Alkylators, and Anti-BCMA
NCCN Guidelines – Late Relapse
Currently Available Drugs for Triple-Class Refractory Myeloma
Class Drug
Nuclear export inhibitor
Antibody-drug conjugate
XPOVIO (selinexor)
Twice-weekly pill
Chimeric antigen receptor (CAR) T cell
Blenrep (belantama b mafodotin)*
Abecma (idecabtage ne vicleucel)
Bispecific antibody
2.5 mg/kg IV over approximately 30 minutes once every 3 weeks
300 to 460 × 106 genetically modified autologous CAR T cells in one or more infusion bags
• For relapsed/refractory myeloma in combination with dexamethasone (after at least 4 prior therapies and whose disease is refractory to at least 2 PIs, at least 2 IMiDs, and an anti-CD38 mAb
• For relapsed/refractory myeloma (after at least 4 prior therapies including an antiCD38 mAb, a PI, and an IMiD
• For relapsed/refractory myeloma (after 4 or more
prior lines of therapy, including an IMiD, a PI, and an anti-CD38 mAb
Tecvayli (Teclistamab) Step up dosing then weekly SQ For relapsed/refractory myeloma (after 4 or more prior
CAR T cell
Carvykti (ciltacabtag ene autoleucel)
0.5 to 1.0 × 106 genetically modified autologous CAR T cells/kg of body weight
Talquetamab lines of therapy, (PI, an IMiD, and an anti-CD38 mAb Elranatamab
IMiD, immunomodulatory agent; PI, proteasome inhibitor; mAb, monoclonal antibody
• For relapsed/refractory myeloma (after 4 or more prior lines of therapy, including a PI, an IMiD, and an anti-CD38 mAb
Emerging Therapies for
Relapsed/Refractory Multiple Myeloma
Bispecific antibodies
• Cevostamab, Alnuctamab, ABBV383, and others
• Target BCMA, GPRC5D, or FcRH5 on myeloma cells and CD3 on T cells
• Redirects T cells to myeloma cells
Cereblon E3 ligase modulators (CELMoDs)
• Iberdomide
• Targets cereblon
• Enhances tumoricidal and immune-stimulatory effects compared with immunomodulatory agents
Small molecule inhibitors
• Venetoclax
• Targets Bcl-2
• Induces multiple myeloma cell apoptosis
CAR T-Cell Therapy and Bispecific Antibodies
Autologous CAR T-Cell Therapy: Underlying Principles
Leukapheresis Manufacturing Infusion
Collect patient’s white blood cells
Isolate and activate T cells Engineer T cells with CAR gene
Tumor cell
Targeting element (eg, CD19, BCMA, CD20)
Spacer
Expand CAR T cells Infuse same patient with CAR T cells
Transmembrane domain
Costimulatory domain (eg, CD28 or 4-1BB)
CD3 ( �� essential signaling domain)
Median manufacturing time: 17-28 days
Patients undergo lymphodepleting (and possibly salvage/bridging) therapy
Majors. EHA 2018. Abstr PS1156. Lim. Cell. 2017;168:724. Sadelain. Nat Rev Cancer. 2003;3:35. Brentjens. Nat Med. 2003;9:279. Park. ASH 2015. Abstr 682. Axicabtagene ciloleucel PI. Tisagenlecleucel PI.
CAR T-Cell Therapy Patient Journey
Fludarabine and Cytoxan are used to create “immunologic space” to
Abecma and Carvykti in Relapsed and Refractory Multiple Myeloma
ORR, overall response rate; PR, partial response; VGPR, very good partial response; CR, complete response; sCR, stringent complete response; MRD, minimal residual disease; PFS, progression-free survival
KarMMa Trial. Munshi NC et al. N Engl J Med. 2021;384:705.
CARTITUDE-1 Trial. Berdeja JG et al. Lancet. 2021;398:314; Martin T et al. J Clin Oncol. June 4, 2022 [Epub ahead of print].
CAR T: Expected Toxicities
Cytokine release syndrome (CRS) Neurotoxicity (ICANS)
Cytopenias
Infections
CRS ICANS
Onset 19 days after CAR T-cell infusion 29 days after CAR T-cell infusion
Duration 511 days 317 days
Symptoms
• Fever
• Difficulty breathing
• Dizziness
• Nausea
• Headache
• Rapid heartbeat
• Low blood pressure
• Headache
• Confusion
• Language disturbance
• Seizures
• Delirium
• Cerebral edema
Management
• Actemra (tocilizumab)
• Corticosteroids
• Supportive care
• Antiseizure medications
• Corticosteroids
*Based on the ASTCT consensus; †Based on vasopressor; ‡For adults and children >12 years; §For children ≤12 years; ‖Only when concurrent with CRS
Xiao X et al. J Exp Clin Cancer Res. 2021;40(1):367. Lee DW et al. Biol Blood Marrow Transplant. 2019;25:625; Shah N et al. J Immunother Cancer. 2020;8:e000734.
CAR-T access remain an issue
MM CAR-T infusion volume in 2021 10-50 (<5,50-100)
Number of FDA approved CAR-T slots given per month 1 (0-4)
Patients on wait list (FDA
Duration a patient is on waiting list 6 (2-8) months
Outcomes of patients on wait list
Survey of 20 centers. Responses from 17 centers.
Transplant vs CAR T Cells
Cellular therapies
Patient’s cells collected
T-cell therapy
Autologous stem cell transplantation
Types of cells collected T cells* Stem cells†
Collected cells are genetically engineered in a lab Yes No
Patient given chemotherapy before cells are infused back into patient Yes, lymphodepleting therapy Yes, melphalan
When in the course of myeloma is this usually done?
Side effects of treatment
After multiple relapses As part of initial treatment
Cytokine release syndrome; confusion Fatigue, nausea, diarrhea
*An immune cell that is the “business end” of the system, in charge of maintaining order and removing cells.
†Precursor cells that give rise to many types of blood cells. We actually collect CD34+ve cells.
Bispecific and Trispecific Antibodies
There are currently 3 approved bispecific antibodies:
Teclistamab (Tecvayli)
Talquetamab (Talvey)
Elranatamab (Elrexfio)
Earlier Line Use of CAR-T: Ide-cel KarMMa 3
MM patients with 2-4 prior lines of therapy Ide-cel (N=254)
Randomized 2:1
SOC treatment (5 options) (N=132) Primary
Cross-over allowed at progression in SOC arm
56% patients crossed over in SOC arm, confounding OS analysis
Pre-specified analysis adjusted for cross-over showed improved OS with ide-cel vs SOC Rodriguez-Otero et al. ASH
CARTITUDE- $
Earlier Line Use of CAR-T: Cilta-cel CARTITUDE 4
MM patients with 1-3 prior lines of therapy Cilta-cel
Earlier line compared to KarMMa-3
Randomized 1:1
No crossover allowed
Bispecific Antibodies
Bispecific antibodies are also referred to as dual specific antibodies, bifunctional antibodies, or T-cell engaging antibodies
Bispecific antibodies can target two cell surface molecules at the same time (one on the myeloma cell and one on a T cell)
Many different bispecific antibodies are in clinical development; none are approved for use in myeloma
Availability is off-the-shelf, allowing for immediate treatment
BCMA, GPRC5D, or FcRH5
Examples:
• Elranatamab
• Teclistamab
• TNB-303B (ABBV-383)
• REGN5458
• Cevostamab
• Talquetamab
Now Approved: Tecvayli, the First Bispecific Antibody
Drug Formulation Approval
Tecvayli (teclistama b)* Step-up dosing† the first week then once weekly thereafter by subcutaneous injection
• For relapsed/ refractory myeloma (after 4 or more prior lines of therapy, including an IMiD, a PI, and an anti-CD38 mAb)
IMiD, immunomodulatory agent; PI, proteasome inhibitor; mAb, monoclonal antibody
*Black box warning: cytokine release syndrome; neurologic toxicities
†Patients are hospitalized for 48 hours after administration of all step-up doses.
Tecvayli is available only through a restricted distribution program.
MajesTEC-1: Duration of Response
• Overall median DOR of 18.4 months (95% CI: 14.9–NE), and was not yet mature with data from 71 patients (68.3%)
• 12-month event-free rate:
• Overall:
MajesTEC-1: Overall Safety Profile; watch for infections
Teclistamab was well tolerated; discontinuations and dose reductions were infrequent
• 2 patients (1.2%) discontinued due to AEs (grade 3 adenoviral pneumonia; grade 4 PML)
• 1 patient had dose reduction at cycle 21
• The most common AEs were CRS and cytopenias
• Infections occurred in 126 (76.4%) patients (grade 3/4: 44.8%)
• 123 patients (74.5%) had evidence of hypogammaglobulinemia a
• There were 19 deaths due to AEs, including 12 COVID-19 deaths
• 5 deaths due to teclistamab-related AEs:
• COVID-19 (n=2)
• Pneumonia (n=1) • Hepatic failure (n=1)
Elranatamab : Duration of Treatment and Best Overall Response
• Median duration of followup was 12.0 mos (range 0.3–32.3)
• ORR = 64% (95% CI, 50–75); CR/sCR rate = 38% (21/55)
• 54% (7/13) of patients with prior BCMA-directed therapy achieved response
• For responders (n = 35), median TTR = 36 days (range 7–262)
Data cutoff 9/30/2022
Swimmer plot depicts disease assessments relevant to first response, confirmation of response, deepening of response, and best response. Mutational analysis was filtered on functional mutations annotated in OncoKB and normal allele frequency <5% in paired peripheral blood mononuclear cell samples. * Prior anti-BCMA ADC. * Prior BCMA-targeted CAR-T.
MR = minimal response; NE = not evaluable; PD = progressive disease; Q2W = every 2 weeks; REL = relapse; SD = stable disease; TTR = time to response.
Raje N, et al. ASH. 2022: abstract 158.
MonumenTAL-1: ORR With Talquetamab⍭
*Calculated from n =106 responders in each group. QW = weekly.
ORR was similar for QW and Q2W schedules
• Triple-class refractory: 72.6% and 71.0%
• Penta-drug refractory: 71.4% and 70.6%
• ORR was consistent across subgroups including baseline ISS stage III disease, baseline cytogenetic risk, number of prior therapies, and belantamab exposure, except among patients with baseline plasmacytomas
9/12/2022
MonumenTAL-1 Talquetamab⍭: Safety*
CRS
CRS events
• Most CRS events were grade 1/2 and largely confined to step-up doses and first full dose
Non-hematologic AEs
• Low rates of grade 3/4 nonhematologic AEs
• Low discontinuation rates due to AEs Most common AEs were CRS, skinrelated events, nail-related events, and dysgeusia
Hematologic AEs
• Most high-grade AEs were cytopenias
• Cytopenias were generally limited to first few cycles
Bispecific Antibodies: >20%
*Based on a recent sampling
Bispecific Antibodies: Expected Toxicities
• Cytokine release syndrome (CRS)
• Neurotoxicity (ICANS)
• Usually occurs within first 1–2 weeks
• Frequency (all grade and grade 3–5) higher with CAR T
• Cytopenias
• Target unique
• For example, rash, taste disturbance seen with GPRC5D, but not with BCMA
• Infections
• Incidence for bispecifics at RP2D not yet known
• Viruses: CMV, EBV
• PCP/PJP
• Ongoing discussions regarding prophylactic measures
Anti-infectives
Similarities and Differences Between CAR T-Cell Therapy and Bispecific
Antibodies
How given One-and-done IV or SC, weekly to every 3 weeks until progression Where
Key Points – CAR T and Bispecifics
CAR T and bispecific antibodies are very active even in heavily pretreated patients.
Side effects of CAR T cells and bispecific antibodies include cytokine release syndrome, confusion, and low blood counts, all of which are treatable.
Abecma and Carvykti are only the first-generation CAR T cells and target the same protein. Different CAR Ts and different targets are on the way.
Bispecific antibodies represent an “off-the-shelf” immunotherapy; Tecvayli was approved in October 2022, and now Talvey and Elrexfio in August 2023
Several additional bispecific antibodies are under clinical evaluation.
The Evolution of Myeloma Therapy
Bortezomib
Lenalidomide
Carfilzomib
Pomalidomide
Lenalidomide
Bortezomib
Ixazomib
Lenalidomide + PI
SCT +/- More induction
Carfilzomib
Combinations
Selinexor
Panobinostat
Daratumumab
Ixazomib
Elotuzumab
Isatuximab
Idecabtagene autoleucel
Ciltacabtagene autoleucel
Teclistamab
Talquetamab
Elranatamab
CAR T or Bispecifics?
Daratumumab?
Novel CAR T Cell Therapies
Bispecific/Trispecific Antibodies
CelMod Agents
Targeting BCL2
Multiple small molecules
Belantamab combinations
ASCT, autologous stem cell transplant; CAR, chimeric antigen receptor; Cy, cyclophosphamide; d- daratumumab; D/dex, dexamethasone; isa, isatuximab; K, carfilzomib; M, melphalan; PD-L1, programmed death ligand-1; PI, proteasome inhibitor; Rev, lenalidomide; V, bortezomib. Speaker’s own opinions.
Partnering with the IMF
Sylvia Dsouza
Vice President, Development
International Myeloma Foundation
Engaging & Partnering with the IMF
Sylvia Dsouza, Vice President, Development
WHO AM I & WHAT DO I DO?
Vice President of Development for the IMF
Securing philanthropic support and resources for the IMF through diverse mechanisms
Oversee a team of passionate and determined fundraising professionals who are committed to advancing the mission of the IMF
Have the incredible honor of working with dedicated volunteers from the US and across the globe.
3 Ways to Engage
Philanthropy
• Make a philanthropic gift to support research, education, advocacy or patient support programs.
• Organize or participate in fundraising events such as walks, runs, golf tournaments, community block parties, or galas.
• Create a fundraising campaign online to raise awareness and funds.
Volunteer
• Join your local support group/become a Support Group Leader
• Join our grassroots patient Advocacy program
• Volunteer your time at local events organized by the IMF to engage the community
• Engage on social media to connect with others affected by myeloma and spread awareness and empower patients with knowledge and resources.
Intellectual capacity
• Offer your expertise as a speaker or panelist at events.
• Be a beta tester for various new tools and products and provide reviews and feedback
Philanthropy Fuels Needle
Peer-to-Peer Fundraising
• Peer-to-Peer Fundraisers are created from YOUR ideas. Starting a Fundraiser is easy and fun. They also make a world of difference in the myeloma community.
• Engage your family, friends, co-workers, your network who honor your journey with myeloma and want to support you. Let them show you that you are not alone.
Join the HOPE Society (Recurring Monthly & Annual Giving Program)
• Help us cultivate the future by joining the International Myeloma Foundation's Hope Society.
• Monthly and annual gifts support IMF core programs, including educational events, publications, the toll-free InfoLine, and more.
• Start with a monthly contribution and when ready turn it into a yearly commitment. You will be a part of likeminded individuals united in the quest to find a cure for myeloma and a better quaity of life for all myeloma patients.
Transformative Gifts (Major Giving and Principal Giving)
• Gifts can be designated toward a specific program, project or initiative .
• Is there something specific that resonates deeply with you and you want to see change happening?
• Gifts can also be unrestricted, expendable and/or an endowment
P2P
• Laughs 4 Life -- 8 years, $483,850!
Peer-to-Peer (P2P) and Monthly & Annual Giving
• Miracles for Myeloma -- 12 years, $804,422!
• Iceland Cycling Expedition-- Inaugural Event and opportunity to be a part of a group of patients, doctors, nurses to train together, bike across Iceland and raise money to support iStopMM cure trials.
• Hole In One – Inaugural golf tournament that has raised almost $40k in three months.
Monthly & Annual Giving – HOPE Society
• Join our flagship monthly and annual giving program, the HOPE Society.
• Get invited to Regional Salon Dinners in your area with IMF leadership and KOLs.
• Receive exclusive updates on research and trials fresh off the press.
• Play a pivotal role in supporting our four pillars.
• Support long-term initiatives that make a lasting difference.
Major Giving - Black Swan Research Initiative
The Black Swan Research Initiative was funded by a Board member/donor who was a visionary and saw the need for the IMF to launch this initiative
The IMF's Black Swan Research Initiative serves as a conductor of sorts to this orchestra of collaborating experts in the field of myeloma. The BSRI sponsors more than 50 projects around the world aimed at curing multiple myeloma. Among them:
SPAIN: The CESAR trial uses the combination of Kyprolis, Revlimid, and dexamethasone plus autologous stem-cell transplant to treat high-risk smoldering multiple myeloma, incorporating minimal residual disease (MRD) testing using next-generation flow cytometry (NGF) and Blood testing for routine monitoring USA: The ASCENT trial tests early intervention in high-risk smoldering multiple myeloma.
ICELAND: Launched in 2016, the iStopMM project identifies and treats multiple myeloma at the earliest signs of disease.
GERMANY: Studies are exploring long-term survival and hereditary risk factors in multiple myeloma.
AUSTRALIA: Identifying mechanisms of the progression of multiple myeloma and testing DNA mutations in the blood.
SINGAPORE: Hub for the Clinical Trials Network in Asia for the IMF’s Asian Myeloma Network (AMN) program by Prof Wee Joo Chng. A collaboration of eight countries (or regions), the AMN is unique in providing access to novel agents in a clinical trial setting throughout Asia. In addition, research projects appropriate for the region are conducted to improve outcomes and achieve a cure.
What will your legacy be?
Planned Giving
• Join the Brian D. Novis Legacy Society and make a planned gift!
• Gain immediate tax benefits
• Potentially increase your income during your lifetime.
• Continue to fund our core programs and four pillars.
• Make a bequest (a gift from your estate)
• Include a provision in your will or living trust.
• Designate us as a beneficiary of a life insurance policy, or retirement plan (IRA, 401(k), or 403(b).
• Include us in your estate planning, one of the most profound ways to support the people and causes important to you.
Corporate and Foundation Gifts
• Your organization can contribute a corporate gift or foundation grant
• Provide seed funding that is necessary to accelerate the path to a cure.
$122,150 raised toward goal of $250,000!
• Each year, patients and care partners gather to share their stories, experiences, and knowledge. It is through the tireless dedication of our support group leaders that we’ve been able to extend our reach and foster connected communities across the world.
Support Group Leaders Summit 25th Anniversary
"The Support Group Leaders Summit has empowered me to network with leaders nationwide, learn from their experiences, and appreciate the dedication of the International Myeloma Foundation (IMF) to patients, caregivers, and families affected by myeloma."
Start the Conversation
We welcome you to learn more about our programs, projects, and initiatives at the IMF and find alignment with your own myeloma journey as well as ways to deepen and strengthen your engagement with us. Reach out to the IMF Development Team to start a conversation on how you can make a difference in the lives of the people impacted by myeloma.
Sylvia Dsouza Vice President, Development sdsouza@myeloma.org (310) 947.4126
Kate Fitzpatrick Assistant Director, Monthly and Annual Giving kfitzpatrick@myeloma.org (818) 487-7455 x 303
Kimberly Francis Assistant Director, Peer-to-Peer Fundraising kfitzpatrick@myeloma.org (818) 487-7455 x304
Matthew Broughton Assistant Director, Operations mbroughton@myeloma.org (818) 487-7455 x299
QUESTIONS?
Seasons of Multiple Myeloma
Beth Faiman, PhD, MSN, APN-BC, AOCN®, BMTCN®, FAAN, FAPO
Cleveland
Clinic Taussig Cancer Institute
IMF Nurse Leadership Board Member
Wintery Mix of Treatment Options Spring into Managing Side Effects
Summer of Success
Wintery Mix of Treatment Options
Diverse and Complex Treatment Combinations
Myeloma Treatment Common Combinations
Velcade® (bortezomib)
DVRd, VRd, Vd
Lenalidomide DVRd, VRd, Rd
Kyprolis® (carfilzomib) KRd, Kd, DKd, Isa-Kd
Pomalyst® (pomalidomide) Pd, DPd, EPd, PCd, Isa-Pd
Darzalex® (daratumumab) DVRd, DRd, DVd, DPd, DVMP, DKd
Ninlaro®(ixazomib) IRd
Empliciti® (elotuzumab) ERd, EPd
Xpovio® (Selinexor) XVd, XPd, XKd
Sarclisa® (Isatuximab) Isa-Kd, Isa-Pd
Blenrep® (Belantamab mafodotin) Bela-d
Abecma® (Idecabtagene Vicleucel) --
Carvykti™ (ciltacabtagene autoleucel) --
Elrexfio™ (elranatamab) --
Tecvayli® (teclistamab)
Talvey™ (talquetamab)
Venclexta® (venetoclax) Vd + ven
New agents or regimens in clinical trials are possible options
ASCT = autologous stem cell transplant; Bela = belantamab; C = cyclophosphamide; D = daratumumab; d = dexamethasone; E = elotuzumab; Isa = isatuximab; I = ixazomib; K = carfilzomib; M = melphalan; P = pomalidomide; R = lenalidomide; V = bortezomib; ven = venetoclax.
Stem Cell Transplant
ELIGIBILITY
Measuring Treatment Response
Determining Transplant Eligibility
Insurance Authorization Collecting Stem Cells
TRANSPLANT
High Dose Chemotherapy
Stem Cell Infusion
Supportive Care Engraftment
Duration: Approximately 2 weeks
Location: Transplant Center
Duration: Approximately 3-4 weeks
Location: Transplant Center
P H A S E 1 P H A S E 2 P H A S E 3
Restrengthening
Appetite recovery “Day 100” assessment
Begin maintenance therapy
Duration: Approximately 10-12 weeks
Location: HOME
CAR T: Another Treatment Approach
Ask for a referral to CAR Tcell center as soon as it is possible as next treatment option (ie, before relapse)
Manufacturing takes ≈ 4 to 6 weeks
Bridging therapy may be needed
T-Cell Collection
No driving for 8 weeks
“One
& Done” with continued monitoring
• Away from home
• Often some hospital stay
• Care Partner needed
• Side effect management
• CRS, ICANS
• Low blood counts
• Fatigue and fever
• Some patients need ongoing transfusion support
Bispecific Antibodies
• Different bispecific antibodies have differences in efficacy, side effects
– Available after 4 prior lines of therapy (or clinical trial)
– About 7 in 10 patients respond
– Off-the-shelf treatment; no waiting for engineering cells
– CRS and neurotoxicity
– Risk of infection
• BCMA target: greater potential for infection
– Tecvayli® (teclistamab)
– Elrexfio™ (elranatamab)
BISPECIFIC ANTIBODIES
• GPRC5D target: potential for skin and nail side effects, GI issues of taste change, anorexia and weight loss
– Talvey™ (talquetamab)
CAR T and Bispecific Antibodies: Unique Side Effects
CRS is a common but often mild & manageable side effect
CAR = chimeric antigen receptor; CRS = cytokine release syndrome. Oluwole OO, Davila ML. J Leukoc Biol. 2016;100:1265-1272. June CH, et al. Science. 2018;359:1361-1365. Brudno JN, Kochenderfer JN. Blood. 2016;127(26):3321-3330. Brudno JN, Kochenderfer JN. Blood Rev. 2019:34:45-55. Shimabukuro-Vornhagen, et al. J Immunother Cancer. 2018;6:56. Lee DW, et al. Biol Blood Marrow Transplant. 2019;25:625-638.
CAR T and Bispecific Antibodies: Unique Side Effects
Spring Into Managing Side Effects
The Early Bird Gets the Worm: Communicate Proactively
with Your Healthcare Team
Your team may be able to help, but only if they know how you feel.
Unmanaged Myeloma can cause:
• Calcium elevation
• Renal dysfunction
• Low blood counts
• Infection Risk
• Blood clots
• Bone pain
• Neuropathy
• Fatigue
How You Feel
Side Effects of Treatment can
cause:
• GI symptoms
• Renal dysfunction
• Low blood counts
• Infection Risk
• Blood clots
• Neuropathy
• Fatigue
Tip: Keep a Symptom Diary and bring it to appointments
Tip: proactively discuss common side effects and what to do if they occur
Are Steroids Messing With Your Sunny Disposition?
Steroids enhance the effectiveness of other myeloma therapies
Your provider may adjust your dose. Do not stop or alter your dose of steroids without discussing it with your provider
Steroid Side Effects
• Irritability, mood swings, depression
Managing Steroid Side Effects
• Consistent schedule (AM vs. PM)
• Take with food
• Stomach discomfort: Over-the-counter or prescription medications
• Medications to prevent shingles, thrush, or other infections
• Difficulty sleeping (insomnia), fatigue
• Blurred vision, cataracts
• Flushing/sweating
• Increased risk of infections, heart disease
• Muscle weakness, cramping
• Increased blood pressure, water retention
• Stomach bloating, hiccups, heartburn, ulcers, or gas
• Weight gain, hair thinning/loss, skin rashes
• Increased blood sugar levels, diabetes
Infection Can Be Serious for People With Myeloma
[P]reventing infections is paramount.
Infection remains the leading cause of death in patients with multiple myeloma. Several factors account for this infection risk, including the overall state of immunosuppression from multiple myeloma, treatment, age, and comorbidities (e.g., renal failure and frailty).
IMWG Consensus guidelines and recommendations for infection prevention in multiple myeloma; Lancet Haematol.2022;9(2):143–161.
Infection Prevention Tips
Good personal hygiene (skin, oral)
Environmental control (avoid crowds and sick people; use a high-quality mask when close contact is unavoidable)
Report fever of more than 100.4°F, shaking chills even without fever, dizziness, shortness of breath, low blood pressure to HCP as directed.
As recommended by your healthcare team:
Immunizations:
Flu, COVID, RSV & and pneumococcal vaccinations; avoid live vaccines
Preventative and/or supportive medications (next slide)
Medications Can Reduce Infection Risk
Type of Infection Risk
Viral: Herpes Simplex (HSV/VZV); CMV
Bacterial: blood, pneumonia, and urinary tract infection
PJP (P. jirovecii pneumonia)
Fungal infections
COVID-19 and Influenza
IgG < 400 mg/dL (general infection risk)
ANC < 1000 cells/μL (general infection risk)
Medication Recommendation(s) for Healthcare Team Consideration
Acyclovir prophylaxis
Consider prophylaxis with levofloxacin
Consider prophylaxis with trimethoprim-sulfamethoxazole
Consider prophylaxis with fluconazole
Antiviral therapy if exposed or positive for covid per institution recommendations
IVIg recommended
Consider GCSF 2 or 3 times/wk (or as frequently as needed) to maintain ANC > 1000 cells/μL and maintain treatment dose intensity
Some people receiving BCMA-targeting therapies have experienced infections that are less common like CMV, PJP and fungal infections
Management of Oral Side Effects
Dry Mouth
OTC dry mouth rinse, gel, spray are recommended. Advise patients to avoid hot beverages. Initiate antifungal therapy for oral thrush
Dexamethasone oral solutions “swish and spit” have been tried but with no proven benefit yet. Sour citrus or candies before meals are also recommended. Taste Changes
Dietary modifications with small bites, eating upright, and sips with food can help manage symptoms.
Some medications lead to weight gain, others to weight loss.
Dry mouth leads to taste changes which can lead to anorexia. Meet
Dysphagia
Catamero D, Purcell K, Ray C, et al. Presented at the 20th
Myeloma Society (IMS) Annual Meeting Nurse Symposium; September 27–30, 2023; Athens, Greece.
GI Symptoms: Prevention & Management
Fluid intake can help with both diarrhea and constipation and helps kidney function
Diarrhea may be caused by medications and supplements
• Laxatives, antacids with magnesium
• Antibiotics, antidepressants, other (check with provider, pharmacist)
• Supplements: milk thistle, aloe, cayenne, saw palmetto, ginseng
Avoid caffeinated, carbonated, or heavily sugared beverages
Take anti-diarrheal medication if recommended and no cause related to infection
Constipation may be caused by medications and supplements
• Opioid pain relievers, antidepressants, heart or blood pressure medications (check with provider, pharmacist)
• Supplements: Calcium, Iron, vitamin D (rarely), vitamin B-12 deficiency
Increase fiber
• Fruits, vegetables, high fiber whole grain foods
• Fiber binding agents – Metamucil®, Citrucel®, Benefiber®
Discuss GI issues with healthcare providers to identify causes and make adjustments to medications and supplements
Skin and Nail Side Effects
Possible side effect to some treatments and supportive care medications
Skin Rash:
• Prevent dry skin; apply lotion
• Report changes to your care team
• Medication interruption or alternative, as needed
• Steroids:
– Topical for grades 1-2,
– Systemic and topical for Grade 3
• Antihistamines, as needed
Nail Changes:
• Keep your nails short and clean. Watch for “catching and tearing”
• Apply a heavy moisturizer like Vaseline or salve. Wear cotton hand coverings to bed
• A nail hardener may help with thinning
• Tell the team if you have signs of a fungal infection, like thickened or discolored nails
Photos: Mount Sinai Hospital, NY, NY
Feel Like a Spring Chicken: Prevent and Manage Pain
Pain can significantly compromise quality of life
Sources of pain include bone disease, neuropathy and medical procedures
• Management
– Prevent pain when possible
• Bone strengtheners to decrease fracture risk
• Antiviral to prevent shingles
• Sedation before procedures
– Interventions depend on source of pain
• May include medications, activity, surgical intervention, radiation therapy, etc
• Complementary therapies (Mind-body, medication, yoga, supplements, acupuncture, etc)
• Scrambler therapy for neuropathy
Tell your healthcare provider about any new bone or chronic pain that is not adequately controlled
Peripheral Neuropathy Management
Peripheral neuropathy happens when there is damage to nerves in the extremities (hands, feet, limbs). Damage can be the result of myeloma, treatment or unrelated conditions (i.e. diabetes).
Symptoms:
• Numbness
• Tingling
• Prickling sensations
• Sensitivity to touch
• Burning and/or cold sensation
• Muscle weakness
Prevention / management:
• Bortezomib once-weekly and/or subcutaneous administration
• Massage area with cocoa butter regularly
• Neuroprotective Supplements:
– B-complex vitamins (B1, B6, B12)
– Green tea
• Safe environment: rugs, furnishings, shoes
If neuropathy worsens, your provider may:
• Adjust your treatment plan
• Prescribe oral or topical pain medication
• Suggest physical therapy
Report symptoms of peripheral neuropathy early to your healthcare provider; nerve damage from neuropathy can be permanent if unaddressed
Understanding Changes to Kidney Function
• Risk Factors
– Active multiple myeloma (light chains, high calcium)
– Other medical issues (ex: Diabetes, dehydration, infection)
– Medications (MM treatment, antibiotics, contrast dye)
– Poor Nutrition
• Prevention
– Stay hydrated – drink water
– Avoid certain medications when possible (eg, NSAIDs), dose adjust as needed
• Treatment
– Treatment for myeloma
– Hydration
– Dialysis
Many myeloma patients will experience kidney issues at some point; protecting your kidney function early and over time is important
Additional Supportive Care
B, et al. CJON. 2017;21(5)suppl:19-36. Dimopoulous M, et al. Leukemia. 2009;23(9):1545-56. Brigle K, et al. CJON.
B, et al. CJON. 2011;15suppl:66-76. Miceli TS, et al. CJON. 2011;15(4)suppl:9-23.
Faiman B, et al. CJON. 2017;21(5)suppl:19-36.
Summer of Success
Let the Sun Shine In
Fatigue is the most reported symptom.
Sources include anemia, pain, reduced activity, insomnia, treatment toxicity, bone marrow suppression 98.8%
Often, people do not share these symptoms with their providers. Talk to your provider about symptoms that are not well controlled or if you have thoughts of self-harm.
>35% of patients
of patients
Care Partners Are Vital for Success
If you want to go fast, go alone, if you want to go far, go together
• Care partners may help with medical appointments, managing medication, daily living, physical assistance, emotional support, myeloma knowledge, healthy lifestyle, patient advocacy, financial decisions
• Care partners can be a spouse, close relative, a network of people (family, friends, neighbors, church members, etc)
African Proverb
• Caring for the Care Partner
– Recognize that caregiving is difficult/stressful
– Encourage care partners to maintain their health, interests, and friendships
– The IMF has information and resources to help care partners
Cultivate A Care Network
• Multiple studies demonstrate that strong social ties are associated with
– Increased longevity including people with cancer
– Improved adherence to medical treatment leading to improved health outcomes
– Lower risk of cardiovascular diseases
– Increased sense of purpose & life satisfaction
– Improved mood and happiness
– Reduced stress and anxiety
– Enhanced resilience
Martino J, et al. Am J of Lifestyle Med. 2015;11(6):466-475. Yang YC, et al. Proc Natl Acad Sci U S A. 2016;113(3):578583.
Pinquart M and Duberstein PR. Crit Rev Oncol Hematol. 2010; 75(2):122–137.
• Strategies for enhancing social connection
– Deepen existing relationships with family, friends, and loved ones
– Build new relationships by participating in a support group, joining clubs or organizations, or volunteering
Tip: Start with small steps outside your comfort zone. Call a loved one you haven’t spoken to in a while. Invite a person you’d like to know better for lunch, coffee, or a walk.
Hetherington C. Healthnews.
https://healthnews.com/longevity/healthspan/social-connection-andlongevity/#:~:text=Research%20consistently%20demonstrates %20that%20people,of%20fulfillment%20in%20your%20life. Accessed Feb 1 2024.
Enjoy Life’s Bounty
Harvest Good Health
Have a Primary Care Provider & Have Recommended Health Screenings
• Blood pressure
• Cholesterol
• Cardiovascular disease
• Diabetes
• Colonoscopy
• Women specific: mammography, pap smear
• Men specific: prostate
• Vision
• Hearing
• Dermatologic evaluation
• Dental checkups & cleaning
Develop & maintain healthy behaviors
• Good nutrition
• Regular activity
• Quit tobacco use
• Sufficient Sleep (next slide)
An ounce of prevention is worth a pound of cure. Benjamin Franklin
Faiman B, et al. CJON. 2017;21(5)suppl:19-36. Dimopoulous M, et al. Leukemia. 2009;23(9):1545-56. Brigle K, et al. CJON. 2017;21(5)suppl:60-76. Faiman B, et al. CJON. 2017;21(5)suppl:19-36. Faiman B, et al. CJON. 2011;15suppl:66-76. Miceli TS, et al. CJON. 2011;15(4)suppl:9-23.
Plentiful Sleep: Important for Good Health
• Adequate rest and sleep are essential to a healthful lifestyle
• Shortened and disturbed sleep cause
– Increased heart-related death
– Increased anxiety
– Weakened immune system
– Worsened pain
– Increased falls and personal injury
• Things that can interfere with sleep
– Medications: steroids, stimulants, herbal supplements
– Psychologic: fear, anxiety, stress
– Physiologic: sleep apnea, heart issues, pain
• Sleep hygiene is necessary for quality nighttime sleep and daytime alertness
– Engage in exercise but not too near bedtime
– Increase daytime natural light exposure
– Avoid daytime napping
– Establish a bedtime routine - warm bath, cup of warm milk or tea
• Associate your bed ONLY with sleep
– Avoid before bedtime:
• Caffeine, nicotine, alcohol and sugar
• Large meals and especially spicy, greasy foods • Computer screen time
Sleep
Health Disparities in Myeloma
Joseph Mikhael MD, MEd, FRCPC
Chief Medical Officer, International Myeloma Foundation, Professor, Translational Genomics Research Institute,
City of Hope Cancer Center
Health Disparities in Myeloma
Patient and Family Seminars
Joseph Mikhael MD, MEd, FRCPC
Chief Medical Officer, International Myeloma Foundation
Professor, Translational Genomics Research Institute, City of Hope Cancer Center
What are Health Disparities?
•Health disparities are preventable differences in the burden of disease, injury, violence, or opportunities to achieve optimal health that are experienced by socially disadvantaged populations
- Centers for Disease Control (CDC)
•Health equity generally refers to individuals achieving their highest level of health through the elimination of disparities in health and health care
A Call to Action
Facts About African Americans and Myeloma
1. There is a longer time from symptoms to diagnosis among African Americans
2. African Americans and Latino Americans are about 5-6 years younger at diagnosis
3. MM and MGUS are more than 2x as common in African Americans
4. African Americans and Latino Americans are less likely to receive the FOUR T’s: Transplant, Triplets, Trials and CAR Ts
5. African Americans have biologic differences with more t(11;14) and less high-risk cytogenetics with deletion 17p
6. Survival outcomes in African Americans are HALF of what is seen in White Americans
7. African Americans can achieve equal or better outcomes when they receive therapy
M-Power = Myeloma Power
The core vision of this initiative is to improve the short- and longterm outcomes of African American patients with myeloma. We want to empower patients and communities to change the course of myeloma…
Enhance access to optimal care by educating myeloma providers about the disparity and how to reduce it
Engage the community to increase awareness and provide support
Shorten the time to diagnosis by educating primary care providers to recognize the disease and order the right tests
2023 M-Power Community Workshops
April 1, 2023
50+ attended
81% African American
• 100% rated v good or excellent
• 100% learned something new!
June 17, 2023
50+ attended 68% African American
September 24, 2023
35+ attended
41% African American
75+ attended 61% African American
• 80% at the Grace Baptist Church learned of the Workshop through their congregation
• 63% at the Riverside Church location learned of the Workshop from IMF
• 96% of attendees rated the program as excellent
• 92% of the attendees reported learning something new
• 100% plan to share something they learned
• 76% had not previously attended an IMF program
Facebook Live
Education of Primary Care Providers
Our goal is to reduce DELAYS in diagnosis among African Americans by educating the primary care community with a focus on:
• Recognizing the signs and symptoms of myeloma
• Discriminating myeloma from other diagnoses such as diabetes
• Capturing an accurate diagnosis through proper use of testing
• Providing referral guidelines for Hematology and Oncology
• Grand Rounds
• Postcards mailed to 6,000+ PCPs in target cities
• Free PCP CME course “Don’t Miss Myeloma”
• Cobb Institute talk
Talk at NMA Annual Meeting Articles and pending publications
8,000
Learners
Annual Meeting of the National Medical Association
Jane Cooke Wright Symposium on Health Disparities
• Hosted by Dr. Edith Mitchell
• Keynote speaker - Dr. Monica Bertagnolli, the director of the National Cancer Institute (NCI)
• Dr. Mikhael spoke about health disparities in myeloma
Poster Walk
Student research was presented to Yelak Biru, Dr. Mikhael, Dr. Mitchell, Dr. Morgan (CEO of the Cobb Institute) and Dr. Bertagnolli.
M-Power Website:
•Web Stats: Over 40k Page views across main, city sites & myeloma.org
•Google PPC targeted web traffic
Email Stats:
•Total Sent: 18 emails
•Total Audience: 38k*
•Open Rate Avg: 31%*
*Note: We have continued to refine lists, contributing to a more engaged audience as evidenced in the Open Rates (The industry standard high-mark is 21%).
M-Minute Promotion
M-Power Connections
•Total Sent: 19 emails
•Total Audience: 323k
•Open Rate Avg: 38.91% M-Power Related Video
• Total Views: Over 50k
Engage
• Planning for 2024 workshops in New York (Juneteenth) and other cities
• Expand online and social media strategy
Future Direction
Educate
• Primary care program in Charlotte
• Lab based education
• Electronic Medical Record Initiative
sEnhance
• Rolling out the Clinical Trial Mentor (CTM) as part of the Diversity in Clinical Trials initiative
• Nurse equity decision tool
Conclusions
•Health disparities are sadly prevalent across all diseases, but particularly in multiple myeloma
•There are MANY other types of inequity in myeloma, including geography, age, gender, orientation…
•Being aware of these disparities is critical to overcoming them
•The IMF’s M-Power is designed to reduce the inequity with specific emphasis on delayed diagnosis, access to therapy and diversity sensitive clinical care
What Can I Do??
•Be more conscious of the topics of health equity
•Evaluate the opportunities in your experience to reduce disparities
•Support the M-Power movement!
THANK YOU TO OUR SPONSORS!
Saturday Agenda: Afternoon
12:00 – 1:00 PM LUNCH
Reminder: After Lunch, return to designated Break-Out Room
1:00 – 1:40 PM Breakout Sessions #2:
Patients and Care Partners
Breakout A: Patients Only – Lessons Learned
Yelak Biru, 28-year Myeloma Patient & Diamond Ballroom E
Breakout B: Care Partners Only
Teresa Miceli, RN, BSN, OCN - InfoLine Advisor, Nurse Leadership Board; Mayo Clinic-Rochester
Ruby (2nd Floor)
1:40 – 1:45 PM RETURN TO GENERAL SESSION 1:45 – 2:15 PM Wild Card Topic: Practical Aspects of Immunotherapy
Rahma Warsame, MD, Mayo Clinic - Rochester
2:15 – 2:55 PM Ask – the – Experts with Guest Faculty 2:55 – 3:00 PM Closing Remarks & Program Evaluation
LUNCH
Reminder: After Lunch, return to designated Break-Out Room
Breakout A: Patients Only – Lessons Learned
Yelak Biru, 28-year Myeloma Survivor & Michael Tuohy, Patient Advocate & 24-year Myeloma Survivor
Diamond Ballroom E
Breakout B: Care Partners Only
Robin Tuohy, VP Patient Support & Teresa Miceli, RN, BSN, OCN - InfoLine Advisor, Nurse
Leadership Board; Mayo Clinic-Rochester
Ruby (2nd Floor)
Patients Only – Lessons Learned
Yelak Biru, IMF President, CEO & 28-year
Myeloma Patient
Wild Card Topic: Practical Aspects of Immunotherapy
Rahma Warsame, MD
Mayo Clinic – Rochester, MN
PRACTICAL ASPECTS OF IMMUNOTHERAPY
Rahma Warsame, M.D. Associate Professor of Medicine & Oncology
July 20th, 2022
NO DISCLOSURE
• Overview of treatment options
LEARNING
OBJECTIVE
• Basics of Immunology
• Timing and optimal candidate for different immune based therapy
• Unique toxicities
PLASMA CELL –
BASICS
Plasma cell: terminally differentiated B-cell that secretes
Immunoglobulins (Ig factory)
• Immunoglobulins
• Heavy chain
• IgM, IgG, IgA, IgD, IgE based on type of heavy chain
• Light chain
• Kappa and lambda
RSR = Relative Survival Rate
MULTIPLE MYELOMA
• Major advances in treatments and improved survival but no cure
• Survival remains poor for
• Disease with high-risk cytogenetics
• Multidrug refractory disease
MYELOMA TREATMENT PARADIGM
Induction Induction followed by continuous therapy Consolidation Maintenance S C T E l i g i b l e S C T I
Tumor Burden
Alkylators/Cytotoxics
Pillars of Myeloma therapy
OUTCOMES FOR PATIENTS
WHO ARE TRIPLE CLASS REFRACTORY (TCR)
• The median time to development of TCR was 2.9 years from diagnosis of MM
• Median PFS was 4 months and OS was 1 year from TCR status
IMMUNOLOGY BASICS
• Myeloma surface proteins (CD38, BCMA, SLAMF7, etc)
• MM cells use these proteins for cellular communication, survival, and potential target for drugs
• T cells
• Type of white blood cells
• Usual function to fight infections and cancer
• Stimulated by other immune cells to identify target proteins
• Identify cancer through T-cell receptor
• Antibodies
• Proteins produced by plasma cells to fight infections
• Attach to specific protein pathogens and cancer cells
• Very specific (1 antibody has only 1 target protein)
MM cells can:
STRATEGIES TO ESCAPE
IMMUNE SYSTEM
• Decrease surface protein expression
• Mask as normal cell
• Decrease proteins requires to stimulate immune cells
• Express surface proteins to suppress normal immune cell activation
B
CELL MATURATION AGENT (BCMA) IS A FREQUENT TARGET FOR IMMUNOTHERAPY TRIALS IN MYELOMA
• BCMA is member of the TNF receptor superfamily
• Expressed nearly universally on myeloma cells
• Expression largely restricted to plasma cells and some mature B cells
• Play important role in plasma cell survival
CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY
ELIGIBILITY FOR CAR T THERAPY
Disease not likely to progress too quickly
Meets trial guidelines or product labeling
Attempted at least 1 or 2 other lines of therapy that have failed (as per product label)
Is at least 3 months post-SCT (if this was a treatment) risk for graft-versus-host disease
In generally good health (ECOG 0-2)
Has good organ function and lab results
Organ function exams (echocardiogram, pulmonary function tests, brain MRI)
Has a support system for patient journey
Caregiver
Locate hospital or CAR T treatment center and send all relevant patient files Patient and caregiver should review logistical considerations
*In general, more patients would be eligible for CAR T-cell therapy compared to stem cell transplantation **Less patients would be eligible for CAR T cell therapy compared to Bispecific Ab
Dave H, et al. Curr Hematol Malig Rep. 2019. doi.org/10.1007/s11899-019-00544-6, Beaupierre A, et al. Clin J Oncol Nursing. 2019;23(2):27-34, Perica K, et al. Biol Blood Marrow Transplant. 2018;24:1135-1141, Cohen AD. American Society of Clinical Oncology Educational Book 38 (May 23, 2018) e6-e15. doi: 10.1200/EDBK_200889
IT TAKES A VILLAGE
INTAKE
• Non-CAR MDs
• Administrative staff
• CAR-certified MD
• Nurse coordinator
• Social worker
• Financial coordinator Consultation
• Apheresis staff
Bridging Chemotherapy
• Non-CAR MDs
• CAR MDs
• Nursing
• Pharmacy
• CAR MDs
• Cell therapy
• Nursing • Pharmacy
• FACT Acute Care
• CAR MDs
• ICU, Neurology
• Nursing
• Pharmacy
• FDA
• CAR MDs
• Nursing
Adapted from Perica K et al. Biol Blood Marrow Transplant. 2018;24(6):1135-1141.
• Financial Services
• Billing
• Pharmacy Regulation
• Data Management
• FACT, CIBMTR, FDA
CAR T-CELL THERAPY
Remove blood from patient to get T cells
T cell
Antigens
CAR T cells bind to cancer cells and kill them
CAR T cell
Make CAR T cells in the lab
Insert gene for CAR
Chimeric antigen receptor (CAR)
Grow millions of CAR T cells
Lymphodepleting chemotherapy
BCMA/GPRC5D
BISPECIFIC ANTIBODY
CD3
Plasma cell
T-cell
Bispecific antibody
Fc domain
IMMUNE SYNAPSE BETWEEN T-CELLS AND TUMOR
CELLS ESSENTIAL TO BISPECIFIC MEDIATED TUMOR LYSIS
Tian, Z et al. Bispecific T cell engagers: an emerging therapy for management of hematologic malignancies. J Hematol Oncol 14, 75 (2021)
WHAT ARE THE CURRENT OPTIONS?
• Approved drugs
• Selinexor- XPO1 inhibitor
• Belantamab – BCMA Antibody drug conjugate (likely renewal approval DREAM 8)
• Panobinostat – HDAC inhibitor
• Venetoclax off label t(11;14)
• CART – BCMA (Ide-cel, Ciltacel)
• T-cell engagers
• BCMA directed (Teclistamab, Elranatamab)
• GPRC5D Talquetamab
• Clinical trials
• T-cell engagers (BCMA and other targets FcRH5)
• Novel CART (allo CART)
• CELMODs
• Modakafusp alpha
•Who is eligible?
•When is it best to pursue this treatment?
•What order do sequence?
•How do you manage toxicity?
•Where can these treatments be conducted?
WHO IS ELIGIBLE FOR IMMUNOTHERAPY
Refractory to any drug
Must be exposed to: PI and IMiD and CD38 mAb PI and IMiD PI and IMiD and CD38 mAb PI and IMiD and CD38 mAb
Ide-cel Carvykti Teclistamab
Elrantamab Talquetamab
BCMA-DIRECTED CAR T CELLS: CURRENT STATE
18%, G3: 3%
21%, G3-4: 9%
onset, days Onset: 2 (1-10), duration: 3 (1-26) Onset: 8 (6-8), duration: 4 (3-6.5)
RWE has demonstrated similar outcomes in commercially treated patients (ide-cel/cilta-cel) relative to the KarMMa/CARTITUDE-1 trial despite >50% being ineligible for trial inclusion.
RWE, real-world evidence. Munshi NC et al. N Engl J Med. 2021;384(8):705-716; Berdeja JG et al. Lancet 2021;398(10297):314-324; Martin T et al. J Clin Oncol. 2023;41(6):1265-1274; Hansen D et al. J Clin Oncol. 2023;41(11):2087-2120.
IDE-CEL VS CILTA-CEL
• Single binding domain
• ORR ↑
• Median CRS onset ↓
• Outpatient administration ↓
• Cost ↑
Availability
ADE incidence • Patient population
Double binding domain
ORR ↑↑
Median CRS onset ↑
Outpatient administration ↑
Cost ↑↑
Summary: Access to timely treatment will often outweigh the safety and efficacy differences
WHAT ARE UNIQUE CAR-T TOXICITIES
• Cytokine release syndrome (CRS) = >80%
• Immune effector cell associated neurotoxicity (ICANS)
>50%
• Early 3-7 days with CRS
• Delayed– Parkinsonism, Guillain Barre Syndrome, Cranial neuropathy
• Potential second malignancies (T cell lymphoma?)
• Cost (Time, manufacturing, housing at tertiary center
• Prolonged cytopenias and hypogammaglobulinemia
WHY DOES CAR-T NOT ALWAYS WORK ?
MM is too aggressive (progresses before infusion)
Patient T cells are less effective (manufacturing failure, or weakened T cell)
Do not persist long enough
Before dysfunction after response
Loss of target by MM cell
BISPECIFIC AB SUMMARY
Route SC SC SC
Step-up: 0.06 mg/kg > 0.3
mg/kg > 1.5 mg/kg
Dosing
Treatment: 1.5 mg/kg
weekly; transition to biweekly if in CR after 6 months
Step-up: 12 mg > 32 mg > 76 mg
Treatment: 76 mg weekly;
transition to biweekly if PR or better after 6 cycles
Step-up: 0.01 mg/kg > 0.06 mg/kg > 0.4 mg/kg > 0.8 mg/kg (for biweekly dose)
Treatment: 0.4 mg/kg weekly or 0.8 mg/kg biweekly
Other Major Adverse Events
Tecvayli. Prescribing information. Janssen Biotech; February 2024; Moreau P et al. N Engl J Med. 2022;387:495-505; Elrexfio. Prescribing information. Pfizer; August 2023; Lesokhin AM et al. Nat Med. 2023;20(9):2259-2267; Talvey. Prescribing information. Janssen Biotech; August 2023; Chari A et al. N Engl J Med. 2022;387(24):2232-2244.
UNIQUE TOXICITY FOR TALQUETAMAB
Skin Related Events
• Asteatotic eczema
• Dry skin
• Eczema
• Pruritus
• Skin exfoliation
• Skin fissures
• Hyperpigmentation
• Lesions or ulcers
Rash Related
Events
• Contact dermatitis
• Dermatitis
• Erythematous rash
• Generalized exfoliative dermatitis
• Maculopapular rash
• Rash
Chari A et al. N Engl J Med. 2022;387(24):2232-2244.
Nail Related
Events
• Nail bed disorder
• Discoloration
• Dystrophy
• Hypertrophy
• Ridging
• Onycholysis
• Onychomadesis
Oral Toxicity
• Dysgeusia
• Dry mouth
• Dysphagia
• Poor appetite
• Weight loss
PRACTICAL TIPS FOR TALQUETAMAB
• Use ammonium lactate lotion on hands and feet twice daily. Recommend SPF 30 or greater for daily use.
• Nail changes: Recommend maintaining oral hydration with at least 8 glasses of water daily.
• Oral toxicity: Maintain good oral hygiene by brushing and flossing twice daily. Avoid alcohol-based mouthwashes which can worsen dry mouth. If having difficulty swallowing or eating, contact your hematology team immediately.
• Other side effects: low blood counts, increased infection risk, and injection site reactions
BISPECIFIC ANTIBODY PIPELINE
Bispecific Antibody Targets Route of Administration
ABBV-383 (TNB-383B) BCMA x CD3 IV
Alnuctamab (CC-93269)
Linvoseltamab (REGN5458)
Cevostamab (BFCR4350A)
(RO7425781)
FcRL5, fragment crystallizable receptor-like 5.
Lee H et al. Hematology Am Soc Hematol Educ Program. 2023(1):332-339.
x CD3 IV/SC
x
BISPECIFIC AB VS CART CONSIDERATIONS?
Bispecific T cell Ab CAR-T
Off-the-shelf option
Manufacturing limitations, limited slots, manufacturing failure up to 10% *
Production times for CAR-T vary from 4 to 6 weeks
No Bridging Likely need interim bridging treatment until CART infusion
IMMUNOTHERAPY SEQUENCING
Overall Response Rate
FUTURE IS BRIGHT
Many more novel therapies on the horizon
QUESTIONS & ANSWERS
Ask – the – Experts Panel
Led by Dr. Joseph Mikhael
Guest Faculty:
Morie Gertz,
MD
Jeffrey Zonder, MD
Jonathan Kaufman, MD
Beth Faiman, PhD, MSN, APN-BC,
BMTCN, AOCN, FAAN, FAPO
Rahma Warsame, MD
EVALUATION
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