ASCO EHA and myeloma treatment in a time of COVID-19

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

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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?

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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!

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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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