ASCO, EHA and myeloma treatment in a time of COVID-19
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Today’s Speakers
Joseph Mikhael
Brian GM Durie
Craig Cole
Chief Medical Officer International Myeloma Foundation
Board Chairman International Myeloma Foundation
Michigan State University Breslin Cancer Center
Thank you to our sponsors!
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Today’s Agenda ASCO/ EHA Highlights Late-breaking abstracts Immune therapies Trial updates Impact of SLiM CRAB and MRD COVID-19 Challenges Infection prevention Management adjustments
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Late-Breaking Abstract (LBA-3)
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Late-Breaking Abstract (LBA-3) Key Eligibility Criteria Newly diagnosed myeloma Excluding high-risk patients : [t(14;20); t(14;16); del17p; PCL; LDH > 2] Included t(11;14) and t(4;14); 1q+ not assessed Upfront ASCT excluded [intent for] CRAB features; no SLiM CRAB 5
KRd versus VRd comparison Median Progression Free Survivals Progression-Free Survival (%)
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KRd 32.8 months VRd 31.7 months
80
60
40
20
0 0
6
12
18
24
30
36
42
48
54
60
Time from Randomization (Months) KRd VRd
545 542
401 377
252 243
187 183
Numbers at Risk 127 83 59 114 73 43
38 31
25 26
13 14
3 0
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Treatment-related Adverse Events KRd: Cardio/ Pulmonary and Renal
VRd: Neuro
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VRd vs KRd: Conclusions • In this trial, KRd does not improve PFS compared with VRd • KRd achieved a higher VGPR rate • Higher rate of peripheral neuropathy is seen with VRd, while rate of cardio-pulmonary and renal toxicity is higher with carfilzomib • No difference has been seen in overall survival • Based on this data VRd should remain the standard of care for initial therapy of multiple myeloma A summary of this abstract is also available on the IMF website: https://www.myeloma.org/videos/results-endurance-e1a11-phase-iii-trial-krd-versus-vrd-initial-therapy-ndmm
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Panel Discussion Is this conclusion correct? What about high-risk disease? What about early disease and older patients? Are there other issues?
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Immune Therapies CAR-T: bb2121 and JNJ 4528 Bi-specific antibody: Teclistamab Antibody/drug conjugate: DREAMM-6
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Idecabtagene vicleucel (ide-cel; bb2121), a BCMA-targeted CAR T-cell therapy, in patients with relapsed and refractory multiple myeloma (RRMM): Initial KarMMa results
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bb2121: Overall Results Conclusions Deep and durable responses Target dose of 450 x 106 CAR T cells best Tolerable A summary of this abstract is also available on the IMF website: https://www.myeloma.org/videos/idecabtagene-vicleucel-ide-celbb2121-bcma-targeted-car-t-cell-therapy-patients
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Update of CARTITUDE-1: A phase Ib/II study of JNJ-4528, a BCMA-directed CAR-T-cell therapy, in relapsed refractory multiple myeloma
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CARTITUDE-1: Overall Results Response Rate
Minimal Residual Disease
MRD +
MRD -
A summary of this abstract is also available on the IMF website: https://www.myeloma.org/videos/update-cartitude-1-phase-ibii-study-jnj-4528-bcma-directed-car-t-cell-therapy-0
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CAR-T Comparisons Novel CAR T fully human binder
Krina Patel MD MSc Oral Abstract Session: CAR T in Multiple Myeloma
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Phase I study of teclistamab, a humanized B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in relapsed/refractory multiple myeloma
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Teclistamab: Duration of Response
A summary of this abstract is also available on the IMF website: https://www.myeloma.org/videos/phase-i-study-teclistamab-humanized-b-cell-maturation-antigen-bcma-x-cd3-bispecific
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DREAMM-6: Safety and Tolerability of Belantamab Mafodotin in Combination with Bortezomib/ Dexamethasone in Relapsed/ Refractory Multiple Myeloma (RRMM) Response Rate ORR 78%
Conclusions Acceptable safety profile • Keratopathy managed with dose modifications Deeper responses expected over time A summary of this abstract is also available on the IMF website: https://www.myeloma.org/videos/dreamm-6-safety-tolerabilitybelantamab-mafodotin-combination-bortezomib-dexamethasone
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Panel Discussion ďƒ˜ What are the pros and cons of each type of therapy? ďƒ˜ What will be the future role of these therapies? 19
Clinical Trial Results 20
First-in-human phase 1 study of the novel CELMoD agent CC-92480 combined with dexamethasone (DEX) in patients (pts) with relapsed/ refractory multiple myeloma (RRMM)
A summary of this abstract is also available on the IMF website: https://www.myeloma.org/videos/first-human-phase-i-studynovel-celmod-agent-cc-92480-combined-dexamethasone-patients
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Weekly selinexor, bortezomib, and dexamethasone versus twice weekly bortezomib and dexamethasone in patients with multiple myeloma: Initial results of the phase III BOSTON study
A summary of this abstract is also available on the IMF website: https://www.myeloma.org/videos/weekly-selinexor-bortezomib-dexamethasone-versus-twice-weekly-bortezomib-dexamethasone
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STaMINA PFS by Treatment Received Auto/ Auto
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PFS Landmark Analysis: Len continued beyond 38 mo. vs Not Len stopped
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Primary analysis of the randomized phase II trial of bortezomib, lenalidomide, dexamthasone with/without elotuzumab for newly diagnosed, high-risk multiple myeloma (SWOG-1211) Progression Free Survival
Elo had no added benefit
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Progression Free Survival
A summary of this abstract is also available on the IMF website: https://www.myeloma.org/videos/isatuximab-plus-carfilzomib-dexamethasone-ikema-phaseiii
Positive data with Isa/ KRd Frontline
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Panel Discussion How important are these trial results? CELMoD Selinexor STaMINA SWOG high-risk IKEMA
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Updated results from BELLINI, a phase III study of venetoclax or placebo in combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma Progression Free Survival
Bortezomib/ Dex + Venetoclax 23.2 months
Bortezomib/ Dex 11.4 months
Overall survival benefit for Venetoclax in t(11;14)/ high BCL-2 A summary of this abstract is also available on the IMF website: https://www.myeloma.org/videos/updated-results-bellini-phase-iii-studyvenetoclax-or-placebo-combination-bortezomib
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Daratumumab + bortezomib, thalidomide, and dexamethasone (D-VTd) in transplant-eligible newly diagnosed multiple myeloma (TE NDMM): Baseline SLiM-CRAB based subgroup analysis of CASSIOPEIA. “SLiM” CRAB: ≥ Sixty % CPC; Light chain ratio ≥ 100; > 1 focal lesion on MRI
SLiM Only
MFC, multiparamatric flow cytometry; NR, not reached
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ASCO Poster Abstracts
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Mass spec more sensitive than SPEP/IFE Mass spec positive predicts earlier relapse Conversion MRD - MRD + also predicts relapse A summary of these abstracts are also available on the IMF website: 1. https://www.myeloma.org/videos/analysis-treatment-efficacy-gem-cesar-trial-high-risk-smoldering-multiple-myeloma 2. https://www.myeloma.org/videos/mrd-assessed-mass-spectrometry-versus-next-generations-sequencing-bonemarrow-myeloma 3. https://www.myeloma.org/videos/clinical-implications-loss-minimal-residual-disease-mrd-negativity-multiplemyeloma
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Panel Discussion Do you agree that:
ďƒ˜ Early intervention provides added benefit? ďƒ˜ Sequential MRD testing is most helpful?
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EHA Abstracts Summary
Orals = 15; Posters = 123 6 Orals also presented at ASCO!
Late Breaking Abstract = IKEMA Trial results 33
EHA Abstracts of Note Several on genetics/ single cell studies Many on MRD testing QoL and “Real World” analyses popular Multiple abstracts on Ixazomib (Ninlaro®)
and Belantamab (“Bela Maf”) 34
Single Cell Transcriptomic Analysis of the Multiple Myeloma Bone Marrow Identifies a Unique Inflammatory Stromal Cell Population Associated with Myeloma Cells In-Situ Activated inflammatory stromal cells in the bone marrow: pathogenic myelomaassociated fibroblasts create a favorable micro-environment for myeloma growth 35
Ixazomib vs Placebo as Post-Induction Maintenance Therapy in Newly Diagnosed Multiple Myeloma (NDMM) Patients (PTS) Not Undergoing Autologous Stem Cell Transplant (ASCT): Phase 3 TOURMALINE-MM4 Trial Ixazomib maintenance
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COVID-19 Key Guidance
Wear a mask
Avoid crowds & physically distance 37
COVID-19 Articles Links to articles (open access) 1. 2.
https://www.nature.com/articl es/s41591-020-0965-6 https://www.thelancet.com/jou rnals/laninf/article/PIIS14733099(20)30471-0/fulltext
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COVID-19 Prevention 85-95% of individuals in communities NOT exposed Have a plan to avoid exposure! • Limit new contacts [including friends/family] • Avoid crowds • Wear a mask in public/ unable to distance • Physically distance/ wash hands • Focus on outdoor/ well-ventilated activities • Avoid group travel • Be alert for dangerous situations
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Myeloma Management MGUS OK; Myeloma a risk! Higher risk with co-factors:
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Increasing age Hypertension Diabetes Chronic lung/ kidney disease Obesity
Use telemedicine when feasible Enhance cautions with intensive/ aggressive therapies such as ASCT or CAR T Use oral therapies as much as possible: dex ok! Remember: myeloma disease control is a priority! 40
Resilience will get you through this together! • Take time in your personal space to re-energize • Enhance your social network to bolster strength and action plans Also listen to the “Conversations with Dr. Durie” podcast on how to build personal resilience: https://www.myeloma.org/podcasts/conversations-dr-durie-special-guest-sue-dunnet Image Source: What Makes Some People More Resilient Than Others https://www.nytimes.com/2020/06/18/health/resilience-relationships-trauma.html
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Panel Discussion
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Thank you to our sponsors!
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