Best of 2021 ASCO & EHA

Thank you to our sponsors!

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Virtual ASCO 2021 Total ASCO abstracts for 2021 = 4,782 Myeloma Abstracts = 282  Oral = 26  Poster Discussion = 32  Poster Session = 106  Publication Only = 118 3

Abstracts Overview 1. Immune Therapies • CAR-T • Bispecifics 2. Frontline Therapy • Triplets • Quadruplets 4

Abstracts Overview 3. Monitoring • Mass spectrometry • Imaging 4. Relapsed therapies • Ninlaro®(ixazomib) • Xpovio®(selinexor) 5

Immune Therapies

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Abstract #8005: CARTITUDE-1

https://www.myeloma.org/videos/ciltacabtagene-autoleucel-bcma-directed-cart-therapy-relapsed-refractory-multiple-myeloma-cartitude1

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CARTITUDE-1 Update • • • • •

Median follow-up – 18 months Overall response rate = 98% (!) sCR = 80% Response duration = 66% at 18 months Some newer concerns about delayed toxicities and how to mitigate.

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Idecabtagene vicleucel (ide-cel, bb2121) •

Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T cell therapy, inrelapsed and refractory multiple myeloma: Updated KarMMa results

•

https://www.myeloma.org/videos/idecabtagene-vicleucel-ide-cel-bb2121-bcma-directed-car-t-cell-therapyrelapsed-refractory

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Characteristics of neurotoxicity associated with idecabtagene vicleucel (ide-cel, bb2121)in patients with relapsed and refractory multiple myeloma (RRMM) in the pivotal phase II myeloma KarMMa study

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https://www.myeloma.org/videos/characteristics-neurotoxicity-associated-idecabtagene-vicleucel-patientsrelapsed-refractory

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Idecabtagene Vicleucel (Ide-cel, bb2121), a BCMA-Directed CAR T Cell Therapy, in Patients With Relapsed andRefractory Multiple Myeloma: Updated KarMMa Results

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https://www.myeloma.org/videos/idecabtagene-vicleucel-relapsed-refractory-myeloma-patients-karmma

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KarMMa-4: Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T-celltherapy in high-risk newly diagnosed multiple myeloma

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https://www.myeloma.org/videos/karmma-4-idecabtagene-vicleucel-bcma-directed-car-t-cell-therapy-high-risknewly-diagnosed

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Abstract #8007 - teclistamab

https://www.myeloma.org/videos/updated-phase-1-teclistamab-trial-results-relasped-refractory-multiple-myeloma

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Teclistamab Update • 40 patients • Response rate = 65% • Of responders: • VGPR = 58% • CR/ sCR = 30% • Toxicities acceptable/ manageable for this bispecific 11

Abstract #8006: elranatamab

https://www.myeloma.org/videos/efficacy-safety-elranatamab-bcma-cd3-bispecific-antibody-patients-relapsed-or-refractory

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What’s next for CAR T? • Rollout of approved products • Earlier use

• Next generation CARs 13

Where will bi-specifics fit in?

• Ongoing IV/ SC • Course of therapy – 6 months?

• Toxicity concerns persist?

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Audience Q&A Type and submit your questions here. Click the Q&A icon circled below if you have minimized the “Ask Question” window.

Triplets and Quadruplets

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EHA Late Breaking Abstract

https://www.myeloma.org/videos/overall-survival-results-daratumumab-lenalidomide-dexamethasone-transplant-ineligible-MAIA

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Progression Free Survival (PFS) data 60-month PFS rate

% surviving without progression

100 80 52.5%

60

D-Rd: median, NR 28.7%

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Rd: median, 34.4 months 20

HR, 0.53; 95% CI, 0.43-0.66; P <0.0001

0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 Months No. at risk Rd 369 333 307 280 255 237 220 205 196 179 172 155 146 133 123 113 105 94 63 36 12 4 D-Rd 368 347 335 320 309 300 290 276 266 256 246 237 232 222 210 199 195 170 123 87 51 17

2 5

0 0

• D-Rd continued to demonstrate a significant PFS benefit, with median PFS not reached with D-Rd • These data provide a new PFS benchmark in patients with NDMM who are transplant ineligible

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Overall Survival (OS) data 60-month OS rate 100

% surviving

80

66.3% D-Rd: median, NR

53.1%

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Rd: median, NR 40 20

HR, 0.68; 95% CI, 0.53-0.86; P = 0.0013

0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 Months No. at risk Rd 369 351 343 336 324 317 308 300 294 281 270 258 251 241 232 223 213 183 134 85 42 14 5 D-Rd 368 350 346 344 338 334 328 316 305 302 297 286 280 273 266 255 249 228 170 118 63 22 6

1 1

0 0

D-Rd demonstrated a significant benefit in OS, with a 32% reduction in the risk of death, in patients with NDMM who are transplant ineligible 19

Abstract #8004: CASSIOPEIA Part II

https://www.myeloma.org/videos/daratumumab-maintenance-or-observation-after-treatment-vtd-asct-patients-cassiopeia

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CASSIOPEIA Update Key Point • Dara maintenance – no added benefit with Dara VTd induction/ consolidation

• Does this change thinking about Dara maintenance?

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Audience Q&A Type and submit your questions here. Click the Q&A icon circled below if you have minimized the “Ask Question” window.

Monitoring

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Abstract #8009: STAMINA Trial

MASS-FIX versus standard methods to predict for PFS and OS among multiple myeloma patients participating on the STAMINA trial. https://meetinglibrary.asco.org/record/196625/abstract

Angela Dispenzieri Mayo Clinic Rochester, MN, USA

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MASS-FIX Testing in STAMINA Trial • MASS-FIX excellent independent predictor of PFS and OS • Compared with MRD Testing with NGF * Promising use of simple blood testing 25

Abstract #8010: GEM (Spanish) Trial

Analysis of minimal residual disease in bone marrow by NGF and in peripheral blood by mass spectrometry in newly diagnosed multiple myeloma patients enrolled in the GEM2012MENOS65 clinical trial.

Noemi Puig University of Salamanca Salamanca, Spain

https://meetinglibrary.asco.org/record/195522/abstract

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Mass spectrometry in GEM (Spanish) Trial • Mass Spec and MRD by NGF found to be complementary in assessing outcomes • Patterns of NGF +/- and Mass Spec +/being further studied 27

Abstract #8012

https://www.myeloma.org/videos/prospective-comparison-whole-body-mri-fdg-pet-ct-detection-multiple-myeloma-correlation

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Key questions about imaging • Is WBLDCT (Whole Body Low Dose CT) the standard?

• What about PET/CT versus MRI?

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Audience Q&A Type and submit your questions here. Click the Q&A icon circled below if you have minimized the “Ask Question” window.

Relapsed Therapies

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Ninlaro®(ixazomib)

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Abstract EP963

https://www.myeloma.org/videos/final-analysis-phase-3-tourmaline-mm1-study-investigating-ixazomib-lenalidomide

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Abstract S184

https://www.myeloma.org/videos/mrd-evaluation-during-ixazomib-maintenance-newly-diagnosed-myeloma-tourmaline

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Significant PFS benefit with ixazomib vs placebo in patients converting from MRD+ to MRD– status 1.0

Censored

MRD+ to MRD–

n

Events

24month PFS, %

Median PFS, months

Ixazomib

42

2

97.5

NE

Placebo

18

5

80.1

NE

Ixazomib, MRD+ to MRD–

Probability of PFS

0.8

0.6

HR 0.139, 95% CI 0.026–0.733, p=0.007

Placebo, MRD+ to MRD–

0.4

• There was no significant difference in PFS between ixazomib and placebo among patients with sustained MRD– status

0.2

0.0 0 3 Number of patients at risk Ixazomib, MRD– to MRD– Ixazomib, MRD+ to MRD– Placebo, MRD– to MRD– Placebo, MRD+ to MRD–

6

9

12

15

18 21 24 27 30 Months since randomization

33

36

39

42

45

48

75

72

71

71

69

65

63

57

52

38

28

22

16

3

1

0

0

42

41

41

41

41

40

38

34

32

28

20

11

6

3

2

0

0

43

43

43

42

41

41

38

35

35

24

17

15

5

2

0

0

0

18

16

16

16

16

15

13

13

11

9

6

4

2

0

0

0

0

Xpovio®(selinexor)

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Abstract #8018: STOMP Trial

Oral selinexor, pomalidomide, and dexamethasone (XPd) at recommended phase 2 dose in relapsed refractory multiple myeloma (MM). https://meetinglibrary.asco.org/record/195449/abstract

Darrell White, MD Dalhousie University Halifax, NS, Canada

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Abstract #8038: Selinexor + Kd

https://www.myeloma.org/videos/once-weekly-selinexor-carfilzomib-dexamethasone-xkd-heavily-pretreated-multiple-myeloma

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Abstract #8024: Selinexor + Vd

https://www.myeloma.org/videos/effects-refractory-status-to-revlimid-to-either-XVd-or-Vd-myeloma-treatment-boston-trial

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Abstract #8019: BOSTON Study

Survival among older patients with previously treated multiple myeloma treated with selinexor, bortezomib, and dexamethasone (XVd) in the BOSTON study. https://meetinglibrary.asco.org/record/195458/abstract

Prof. Thierry Facon, MD Université of Lille, CHU Lille, Service des Maladies du Sang, Lille, France

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Selinexor in Elderly: Update • Patients over age 65 years • Excellent results with selinexor + Vd (BOSTON regimen) re: efficacy/ toxicity • Both PFS and OS improved 41

Abstract #8027

Effects of weekly selinexor, bortezomib, dexamethasone (XVd) versus standard twice weekly bortezomib and dexamethasone (Vd) on RASmutated previously treated multiple myeloma (MM). https://meetinglibrary.asco.org/record/195493/abstract

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Audience Q&A Type and submit your questions here. Click the Q&A icon circled below if you have minimized the “Ask Question” window.

Key questions from IMWG Summit • Several items already discussed • Additional points: • Diagnosis/ treatment for HR/ ultra HR SMM (2/20/20 system) • Immune therapy registry and virtual biobank 44

Key questions from IMWG Summit • Additional points: • Role of new MoAbs and new agents (ex. CelMods) • COVID-19 vaccination

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Additional IMF Resources Acronyms & Abbreviations: https://imf-d8-prod.s3.us-west-1.wasabisys.com/2021-03/acronymand-abbrev-3-2021.pdf

Myeloma Terms & Definitions: https://issuu.com/international-myeloma-foundation/docs/myelomaterms-definitions

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Thank you to our sponsors!

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