IMWG Conference Series: ASH 2021

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Thank you to our sponsors!

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ASH 2021 OVERVIEW  Virtual/ Live (hybrid)  879 “myeloma related” abstracts  Many important reports on biology, diagnostics and trials follow-up 3


iStopMM abstracts for ASH  6 ASH Abstracts for 2021  4 oral presentations  Overall results – Abstract #156

 High prevalence of SMM – Abstract #151  No increased COVID with MGUS – Abstract #154  New FreeLite reference levels – Abstract #542

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iStopMM abstracts for ASH  2 poster presentations  Circulating plasma cells – Abstract #2645  Selection bias in prior MGUS studies –

Abstract #1618

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iStopMM: Overall Results Abstract #156  Over 75,000 individuals screened  “MGUS positive” patients randomized (3,725):  No further contact (1,164)  Periodic follow-up (1,159)  Intensive diagnostic testing/ monitoring (1,164) 6 Abstract #156 - https://ash.confex.com/ash/2021/webprogram/Paper152333.html


iStopMM: Overall Results Abstract #156  Many more disease diagnoses in group 3 including:  SMM + active MM ( + amyloid)  Waldenstrom’s

 CLL  Lymphoma (NHL) 7 Abstract #156 - https://ash.confex.com/ash/2021/webprogram/Paper152333.html


iStopMM: Overall Results Abstract #156

8 Abstract #156 - https://ash.confex.com/ash/2021/webprogram/Paper152333.html


Unexpectedly high prevalence of SMM Abstract #151  0.5% in persons over age 40 years

Abstract #151 - https://ash.confex.com/ash/2021/webprogram/Paper148617.html

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No increased occurrence of COVID-19 in MGUS Patients - Abstract #154

10 Abstract #154 - https://ash.confex.com/ash/2021/webprogram/Paper153145.html


Circulating plasma cells in MGUS/ SMM/ MM - Abstract #2645 Discussion of iStopMM data

11 Abstract #2645 - https://ash.confex.com/ash/2021/webprogram/Paper146363.html


Many diverse outcomes of iStopMM Tumor microenvironment Risk scores MGRS

Pain Flow cytometry

Cancer screening

Renal amyloidosis Genetics Mental health Early intervention

Correlative science

Neuropathy Survival

Cardiac amyloidosis

Psychological impact

The significance of the “unknown significance”

Polyclonal immunoglobulins Waldenströms


iStopMM Outcomes Value of screening (from randomized trial) will be clear during 2022 Additional results are highly anticipated including full sequence data and immune monitoring

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Identifying NGF algorithm for MGUS Abstract #541: Spanish Team collaboration  5,114 patients with plasma cell disorders studied  3 parameters identified  In training datasets rates of progression @ 5 years:  “MGUS phenotype” – Zero  “Intermediate/ SMM” – 54%  “Multiple myeloma” – 66% Abstract #541 - https://ash.confex.com/ash/2021/webprogram/Paper150092.html

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High prevalence of MGUS in Black/ AA Cohort Abstract #152: First results of PROMISE Study  2,960 individuals over 40 years screened  High risk with family history included  Prevalance of 10% in PROMISE cohort (BioBank = 9.4%) 15 Abstract #152 - https://ash.confex.com/ash/2021/webprogram/Paper149868.html


CESAR Trial Update: Abstract #1829 Maria-Victoria Mateos, MD, PHD

 PFS 94% @ 55 months  Sustained MRD negative 67% @ 12 months

Abstract #1829 - https://ash.confex.com/ash/2021/webprogram/Paper148423.html

NOTE: Abstract # 2749: IRd in HR SMM -- CR = 21.8% https://ash.confex.com/ash/2021/webprogram/Paper149787.html

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Machine learning tool to predict undetectable MRD - Abstract #1596  Studied in ASCT-eligible MM  Excellent correlations with outcomes.  Effective “weighted” factors:  t(4;14) and/or 17 p  Level of PCs in bone marrow + PB  Immune markers: CD27- ; CD 38+ ; CD56+ Abstract #1596 - https://ash.confex.com/ash/2021/webprogram/Paper145968.html

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Response assessed by IFE, NGF and Mass Spec - Abstract #544

18 Abstract #544 - https://ash.confex.com/ash/2021/webprogram/Paper151557.html


Dara + VRd Frontline: GRIFFIN Abstract #79

 Updated results: Dara + VRd vs. VRd  Now 24 months maintenance – R ± Dara

19 Abstract #79 - https://ash.confex.com/ash/2021/webprogram/Paper149024.html


Dara + VRd Frontline: GRIFFIN Abstract #79

 Updated responses and MRD

20 Abstract #79 - https://ash.confex.com/ash/2021/webprogram/Paper149024.html


MRD Testing in CASSIOPEIA study Abstract #82 – Part 1 and 2 MRD

NOTE: Q8W Dara maintenance did not improve MRD negativity Abstract #82 - https://ash.confex.com/ash/2021/webprogram/Paper147897.html

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Clinical Outcomes after Bispecifics Therapy - Abstract #821 (Mount Sinai, NY)  Data for 64 RRMM patients  ORR of 58% after bi-specific therapy  18 patients transitioned to CAR T: PFS 28.9 months (OS not reached)  Encouraging results  Further studies needed to assess best sequencing Abstract #821 - https://ash.confex.com/ash/2021/webprogram/Paper151585.html

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Therapy after CAR T treatment (ide-cel) Abstract #2743 KarMMa Trial follow-up  68 patients with subsequent therapy including anti-BCMA  PFS 2 longer than 13 months OS = 24.8 – 31 months  Longer follow-up required to assess all outcomes 23 Abstract #2743 - https://ash.confex.com/ash/2021/webprogram/Paper147990.html


Results with talquetamab (anti-GPRC5D + Dara)

Abstract #161: Multi-center trial

 Small study so far: 23 patients  3 dose cohorts  Tolerable safety profile  Promising efficacy Abstract #158: single agent data in 95 patients continues promising results https://ash.confex.com/ash/2021/webprogram/Paper146868.html Abstract #161 - https://ash.confex.com/ash/2021/webprogram/Paper148813.html

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Results with REGN 5458 (BCMA/ CD3) Abstract #160: Multi-center trial  68 patients  ORR = 73.3% (at 96 + 200 mg doses)  CRs noted in 48.1% of responders  Acceptable safety/ tolerability Overall promising results! 25 Abstract #160 - https://ash.confex.com/ash/2021/webprogram/Paper144921.html


Iberdomide (CelMod) in RRMM Abstract #162  Results for 107 patients with relapsed/refractory MM (RRMM)

26 Abstract #162 - https://ash.confex.com/ash/2021/webprogram/Paper147704.html


COVID-19 Status Reports  10 abstracts (including iStopMM)  Follow-up Spanish data 1 over (Abstract #2719)  451 patients  Key factors remain: Male/ Over age 65 years/ Active MM  Poor antibody responses to vaccines; boosters required  Specific concerns about anti-BCMA and anti-CD38  (impact of omicron variant unknown) Abstract #2719 - https://ash.confex.com/ash/2021/webprogram/Paper149192.html

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Summary Takeaways for ASH 2021  Overview  Additional important observations ??

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Thank you to our sponsors!

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