Best of ASH 2021

Thank you to our sponsors!

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ASH 2021 OVERVIEW  Virtual/ Live (hybrid) ASH Annual Meeting & Exposition

 879 “myeloma related” abstracts

 Many important reports on biology, diagnostics and trials follow-up 3

ASH 2021 – Hybrid (live & virtual) ATTENDANCE Live = 211 Virtual = 647

Total = 858

Slides and replay available: ASH Friday Satellite Symposium

4

ASH 2021 – Hybrid (live & virtual)

REGISTERED Live = 120 Virtual = 230

Total = 360

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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 7

The iStopMM team

Prof. Sigurður Kristinsson 8

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

9

iStopMM Overview

Rögnvaldsson S et al. Blood Cancer Journal 2021 – “Monoclonal gammopathy of undetermined significance and COVID-19: a population-based cohort study”

10

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) Abstract #156: Screening for Monoclonal Gammopathy of Undetermined Significance: A Population-Based Randomized Clinical Trial. First Results from the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) Study

11

Diseases revealed by screening RCT* OF MGUS SCREENING, WORK-UP, AND FOLLOW-UP *RCT = RANDOMIZED CLINICAL TRIAL

MM

MM

SMM

SMM

p<0.001 Abstract #151: ASH Abstract and Video Summary

12

Unexpectedly high prevalence of SMM Abstract #151 • •

• •

RESULTS

75,422 (51% of target population) were screened for M-protein and abnormal free light chain ratio 3,725 with abnormal screening were randomized to one of the three arms At the time of analysis, bone marrow sampling was performed in 1,503 individuals 180 were diagnosed with SMM • 110 (61%) men and 70 (39%) women • Median age 70 (range 44-92) • 151 (84%) with M-protein present, median 0.5 g/dL (range 0.01-3.5), 25 (14%) with abnormal FLC analysis only • 116 (64%) with abnormal FLC ratio 13 Abstract #151: ASH Abstract and Video Summary

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

14 Abstract #151: ASH Abstract and Video Summary

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

Abstract #154: Monoclonal Gammopathy of Undetermined Significance and COVID-19: Results from the Population-Based Iceland Screens Treats or Prevents Multiple Myeloma Study (iStopMM)

15

Abstract #541

Definition and Clinical Significance of the MGUS-like Phenotype: A Study in 5,114 Patients (Pts) with Monoclonal Gammopathies Leire Burgos*, Esteban Tamariz-Amador*, Noemi Puig*, Maria-Teresa Cedena*, Tomas Jelínek, Sarah Johnson, Paolo Milani, Lourdes Cordon, Jose J. Perez, Marta Lasa, Rosalinda Termini, Albert Oriol, Miguel-Teodoro Hernandez, Luis Palomera, Rafael Martinez-Martinez, Javier de la Rubia, Felipe de Arriba, Rafael Rios, Maria-Esther Gonzalez, Mercedes Gironella, Valentin Cabañas, Maria Casanova, Isabel Krsnik, Albert Perez-Montaña, Verónica González-Calle, Paula Rodriguez-Otero, Vladimir Maisnar, Roman Hajek, Fritz Van Rhee, Victor Jimenez-Zepeda, Giovanni Palladini, Giampaolo Merlini, Alberto Orfao, Laura Rosiñol, Joan Blade, Joaquín Martínez-Lopez, Juan-Jose Lahuerta, Maria-Victoria Mateos, Jesus F. San Miguel, Bruno Paiva on behalf of the GEM (Grupo Español de Mieloma)/PETHEMA (Programa para el Estudio de la Terapéutica en Hemopatías Malignas) cooperative study group

16

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%

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Abstract #541: Definition and Clinical Significance of the MGUS-like Phenotype: A Study in 5,114 Patients (Pts) with Monoclonal Gammopathies

Circulating tumor cells predict risk of progression in SMM patients > 78% of SMM patients had CTC > Untreated SMM patients with high CTC levels (≥0.02%) showed ultra-high risk of transformation (11 months) vs those with <0.02% CTCs and undetectable CTCs > CTCs were selected as an independent prognostic factor for TTP, together with the M-protein and sFLC ratio (the % of BM tumor cells was not significant)

> Additional Messages: Evaluation of CTCs in PB outperformed quantification of BM tumor burden in SMM and the 2/20/20 model can be replaced by the 2/20/0.02% model. Allows frequent monitoring (evolving pattern) > Thus, CTC assessment should be part of the diagnostic workup of SMM > New SMM model 2/20/0.02% model JJ Garcés ASH 2021 Abstr 76: TTP, time-to-progression; sFLC, serum free-light chain ratio

Abstract #76: Circulating Tumor Cells (CTCs) in Smoldering and Active Multiple Myeloma (MM): Mechanism of Egression, Clinical Significance and Therapeutic EndpointsClinically Relevant Abstract

18

University of Navarra, Spain Prof. Jesús San Miguel

Dr. Bruno Paiva

19

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  Prevalence of 10% in PROMISE cohort (BioBank = 9.4%) 20 Abstract #152: ASH Abstract and Video Summary

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

 PFS = 94% @ 55 months and OS = 95%  Sustained MRD negative 67% @ 12 months

Abstract #1829: Curative Strategy (GEM-CESAR) for High-Risk Smoldering Myeloma (SMM): Carfilzomib, Lenalidomide and Dexamethasone (KRd) As Induction Followed By HDT-ASCT, Consolidation with Krd and Maintenance with Rd

NOTE: Abstract # 2749: IRd in HR SMM -- CR = 21.8% A Phase II Trial of the Combination of Ixazomib, Lenalidomide, and Dexamethasone in High-Risk Smoldering Multiple Myeloma

21

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

Abstract #544: Assessment of Treatment Response By IFE, Next Generation Flow Cytometry and Mass Spectrometry Coupled with Liquid Chromatography in the GEM2012MENOS65 Clinical Trial

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Abstract #79

Daratumumab (DARA) Plus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Patients (Pts) With Transplant-eligible Newly Diagnosed Multiple Myeloma (NDMM): Updated Analysis of GRIFFIN After 24 Months of Maintenance

Additional information can be viewed by scanning the QR code or accessing this link: https://www.oncologysciencehub.com/ ASH2021/Daratumumab/Laubach The QR code is intended to provide scientific information for individual reference, and the information should not be altered or reproduced in any way.

Presented at the 63rd American Society of Hematology (ASH) Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA/Virtual

*Presenting author.

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Abstract #79

GRIFFIN: PFS 88.9% vs 81.2% 2-year PFS rate

• Median follow-up: 38.6 months • Median PFS was not reached in either group

• There is a positive trend toward improved PFS for DRVd/DR versus RVd/R • The separation of the PFS curves begins beyond 1 year of maintenance and suggests a benefit of prolonged DR therapy

% surviving without progression

100

3-year PFS rate

91.6%

81.2%

89.7%

80

D-RVd

88.9%

RVd 60

40

20

HR: 0.46 (95% CI: 0.21-1.01) 0

0

3

6

9

12

15

18

21

24

27

30

33

36

39

42

45

48

52 81

50 79

45 67

34 50

19 29

9 11

2 2

0 0

Months No. at risk RVd D-RVd

103 104

93 97

77 93

72 89

69 89

67 88

62 86

60 85

58 81

24 Presented at the 63rd American Society of Hematology (ASH) Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA/Virtual

GRIFFIN: MRD-negativitya Rates Improved Throughout the DR Maintenance Period

Abstract #79

Patients with MRD negativity, %

70

64% 59%

60

50%

50

21%

11%

10–6

36%

40

10–5

30

22% 20

Patients with MRD negativity, %

80

30% 26% 20%

13%

3%

10–6

15% 10–5

8%

10

MRD-negative (10–5) conversion rate • 29% (15/52) of D-RVd patients and 12% (10/82) of RVd patients who were MRD positive at the end of consolidation became MRD negative after 2 years of DR or R maintenance

0 End of induction

End of consolidation

At 1 year of After 2 years of maintenance maintenance

End of induction

End of consolidation

RVd

D-RVd 10–5 threshold

At 1 year of After 2 years of maintenance maintenance

10–6 threshold

10–5 threshold

10–6 threshold

aThe

threshold of MRD negativity was defined as 1 tumor cell per 105 white cells. MRD status is based on the assessment of bone marrow aspirates by NGS in accordance with International Myeloma W orking Group criteria. Bone marrow aspirates were assessed at baseline, at first evidence of suspected CR or sCR (including patients with VGPR or better and suspected DARA interference), at the end of induction and consolidation, and after 1 and 2 years of maintenance, regardless of response. Median follow-up was 38.6 months, and MRD-negativity rates are among the ITT population (D-RVd, n = 104; RVd, n = 103).

Presented at the 63rd American Society of Hematology (ASH) Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA/Virtual

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Early Data – GMMG-HD7 trial Abstract #463  Isatuximab + VRD versus VRD frontline  660 patients with intention-to-treat analysis (ITT)  MRD negative after induction 50.1% versus 35.6%

26 Abstract #463: ASH Abstract and Video Summary

Abstract #466

Ixazomib plus Lenalidomide/dexamethasone (IRd) versus lenalidomide/dexamethasone (Rd) maintenance after autologous stem cell transplant in patients with newly diagnosed multiple myeloma: results of the Spanish GEM2014MAIN trial L. Rosiñol, A. Oriol, R. Rios, Mª J. Blanchard, I. Jarque, J. Bargay, M.T. Hernández, J. M. Moraleda, E. Carrillo, A. Sureda, J. Martínez-López, I. Krsnik, M.E. González, F. Casado, J.M. Martí, C. Encinas, F. de Arriba, L. Palomera, A. Sampol, Y. González-Montes, E. Cabezudo, Mª V. Mateos, J.F. San Miguel, J.J Lahuerta J. Bladé on behalf of the PETHEMA/GEM group.

ASH Annual Meeting, Atlanta, December 12, 2021

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Abstract #466

PFS from maintenance: Rd vs IRd

5-yrs: Rd 63%, IRd 62%

Median follow-up: 56 months

Rd HR 1.052 (95% CI 0.730-1.577), p=0.785

IRd

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Triple Class Refractory: When All Else Fails Chemotherapy

Doxorubicin, Liposomal doxorubicin

HDAC / ADC XPO inhibitors

Approved BCMA

BCMA Abs TCEs/ADCs

BCMA CARs

Teclistamab* Selinexor + Belantamab* Cilta-cel (JNJ-4528)* Pavurutamab* Dexamethasone Mafodotin LCAR-B38M TNB-383B*

Cyclophosphamide Bendamustine, Melphalan

Venetoclax

PACE, HyperCAD

Panobinostat/ Vorinostat

Ide-cel* (bb2121)

REGN5458* Elranatamab* CC-93269

bb21217

Non-BCMA Zevo-cel (CT053) [Talquetamab]* ALLO-715 [Cevostamab]* ALLO-605 (TurboCAR)

Blue = approved Orange = BCMA approved Green = ongoing clinical trials

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Clinical response to SEL was more favorable for patients after DARA – Abstract # 893

Abstract #893: Rationale for Selinexor Treatment in Daratumumab-Refractory MM Patients Identified By Paired Ex Vivo Drug Sensitivity and RNA-SeqClinically Relevant Abstract

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Patients treated with belamaf + VRd

DREAMM-9: Abstract #2738

Abstract #2738: DREAMM-9: Phase I Study of Belantamab Mafodotin Plus Standard of Care in Patients with Transplant-Ineligible Newly Diagnosed Multiple Myeloma

DREAMM-5 Updates: Bela after + alCOS – promising!

Abstract #897: DREAMM-5 Study: Investigating the Synergetic Effects of Belantamab Mafodotin Plus Inducible T-Cell Co-Stimulator Agonist (aICOS) Combination Therapy in Patients with Relapsed/Refractory Multiple Myeloma

31

Abstract #898

Modakafusp Alfa (TAK-573), an Immunocytokine, Shows Clinical Activity in Patients with Relapsed/Refractory Multiple Myeloma; Updated Results from a First-In-Human Phase 1 Study Dan T. Vogl,1 Jonathan L. Kaufman,2 Sarah A. Holstein,3 Shebli Atrash,4 Omar Nadeem,5 Murali Janakiram,6 Kaveri Suryanarayan,7 Yuyin Liu,7 Sabrina Collins,7 Xavier Parot,7 Maria Chaudhry8 1Abramson

Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; 2Winship Cancer Institute of Emory University, Atlanta, GA, USA; 3University of Nebraska Medical Center, Omaha, NE, USA; 4Levine Cancer Institute, Charlotte, NC, USA; 5Dana-Farber Cancer Institute, Boston, MA, USA; 6University of Minnesota, Minneapolis, MN, USA; 7Takeda Development Center Americas, Inc. (TDCA), Lexington, MA, USA; 8Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.

Oral presentation at the 63rd Annual Meeting of the American Society of Hematology (ASH), December 11–14, 2021 For questions or comments please contact Dr Dan Vogl: Dan.Vogl@pennmedicine.upenn.edu

Abstract #898: ASH Abstract and Video Summary

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Abstract #898

Overall response rate •

ORR with 1.5 mg/kg Q4W modakafusp alfa

Among 29 patients who received modakafusp alfa 1.5 mg/kg Q4W (5 in dose escalation and 24 in ongoing dose expansion):

40

– 11 patients had ≥PR (ORR 38%), including 6 with VGPR and 2 with CR (28% ≥VGPR) Among 26 anti-CD38 mAb-refractory patients, ORR was also 38% (31% ≥VGPR): – Among the 4 patients who received an anti-CD38 mAb in their most recent line of therapy, 1 achieved a CR, and 2 achieved a VGPR (ORR 75%) •

Of the 15 patients with prior anti-BCMA therapy, 3 (20%) had a VGPR

ORR 38%

6.9

7.7

30

Patients, %

•

ORR 38%

20

20.7

≥VGPR 28%

≥VGPR ORR 20% 31% 23.1

10

20.0 10.3

≥VGPR 20%

7.7

0 All patients (N=29)

Anti-CD38 mAb- Anti-BCMA exposed refractory patients patients (n=26) (n=15) PR

VGPR

CR

CR, complete response; PR, partial response; VGPR, very good partial response

Vogl DT, et al. Blood 2021;138(Suppl.1):898

33

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 #161: Phase 1b Results for Subcutaneous Talquetamab Plus Daratumumab in Patients with Relapsed/Refractory Multiple Myeloma

Abstract #158: single agent data in 95 patients continues promising results Abstract #158: ASH Abstract and Video Summary

34

Abstract #84

Early, Deep, and Durable Responses, and Low Rates of Cytokine Release Syndrome with REGN5458, a BCMAxCD3 Bispecific Antibody, in a Phase 1/2 First-in-Human Study in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Jeffrey A. Zonder, MD1, Joshua Richter, MD2, Naresh Bumma, MD3, Jason Brayer, MD, PhD4, James E. Hoffman, MD5, William I. Bensinger, MD6, Ka Lung Wu, MD7, Linzhi Xu, PhD8, Dhruti Chokshi, BS8, Anita Boyapati, PhD8, Damien Cronier PhD8, Yariv Houvras MD, PhD8, Karen Rodriguez Lorenc, MD8, Glenn S. Kroog, MD8, Madhav V. Dhodapkar, MD9, Suzanne Lentzsch, MD, PhD10, Dennis Cooper, MD11, Sundar Jagannath, MD2 1Karmanos

Cancer Institute, Detroit, MI, USA; 2Icahn School of Medicine at Mount Sinai, New York, NY , USA; 3The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA; 4H. Lee Moffitt Cancer Center, Tampa, FL, USA; 5University of Miami Health System, Miami, FL, USA; 6Swedish Center for Blood Disorders and Stem Cell Transplants, Seattle, WA, USA; 7Ziekenhuis Netwerk Antwerpen Stuivenberg, Antwerp, Belgium; 8Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 9Emory University School of Medicine, Atlanta, GA, USA; 10Columbia University Medical Center, New York, NY, USA; 11Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA

ClinicalTrials.gov ID: NCT03761108 This study was funded by Regeneron Pharmaceuticals, Inc. Medical writing support was provided by Lewis Cawkwell of Arc, a division of Spirit Medical Communications Group Limited, and funded by Regeneron Pharmaceuticals, Inc. Presented at the 63rd ASH Annual Meeting, December 11–14, 2021, Atlanta, Georgia, USA. Abstract #160

Abstract #84: ASH Abstract and Video Summary

35

Abstract #84

Phase 1 efficacy

BOR per modified IMWG criteria (%)

8%

70

8%

60

ORR* = 48% 50 40

20%

ORR* = 29% 30 20 10

42% 4%

13% 24%

13% 4%

17%

Patients’ duration of response (N=37)

ORR* = 75%

80

Response

0

sCR

CR

VGPR

PR

SD

NE

No response yet

MR

Arrows indicate that patient is still on treatment

3–12 mg (n=24)

24–96 mg (n=25)

200–800 mg (n=24)

0

1

2

3

4

5 6

7

8

9 10 11 12 13 14 15 16 17 18 19 20 21 22

Dose level Intention-to-treat analysis Data cut-off: 30 September 2021. *Full analysis set - includes all patients who had opportunity for response assessment at 4 weeks.

BOR, best overall response; CR, complete response; IMWG, International Myeloma Working Group; MR, minimal response; NE, not evaluable; ORR, objective response rate; PR, partial response; sCR, stringent CR; VGPR, very good partial response; SD, stable disease..

Treatment duration (months)

36 Observed median duration of follow-up (range): 3 months (0.7–22.1)

Summary of Bispecific Antibodies in R/R MM Drug

Target

Median prior lines, n

Dosing

ORR, %

CRS, %

Neurotoxicity, %

Notes

65 @ RP2D (70 @ other IV/SC doses)

70 @ RP2D (no grade 3)

2.5 @ RP2D (0 in other SC doses)

SC dosing!

Q3W, allowed for CrCl 30

Teclistamab1 (n = 40 RP2D)

BCMA

5 (2-11)

SC QW for RP2D

TNB-383B2 (n = 58, 15)

BCMA

6 (3-15)

Q3W

80 @ higher doses (n = 15)

45 (no grade 3)

0

REGN-54583 (n = 49, 8)

BCMA

5

Q2W

63 @ highest doses (n = 8)

39 (no grade 3)

12

Pavurutamab/ AMG-7014 (n = 85, 6)

BCMA

6 (2-25)

QW

83 @ most recent doses (n = 6)

64 (9% grade 3)

3.8

Elranatamab5 (n = 30)

BCMA

8 (3-15)

SC weekly

70 @ ≥215 μg/kg

73

20

SC dosing!

6 (2-17)

SC weekly RP2D: 450 μg/kg

53.3 all SC doses (70.0 @ RP2D)

67 all SC (73 @ RP2D) (3% grade 3 @ RP2D)

4.9 all SC (7 @ RP2D)

SC dosing! 16% of pts @RP2D had prior BCMA tx Some grade 3 skin rash, oral toxicity, back pain

Q3W

53, higher doses 61, highest dose (n = 18) 63 in prior BCMA (n = 8)

76 (2% grade 3)

28

21% with prior BCMA tx

Talquetamab6 (n = 82 all SC, 30 RP2D) Cevostamab7 (n = 53, 34)

GPRC5D

FcRH5

6 (2-15)

1. Usmani. Lancet. 2021;398:665. 2. Rodriguez. ASH 2020. Abstr 293. 3. Madduri. ASH 2020. Abstr 291.

4. Harrison. ASH 2020. Abstr 181. 5. Bahlis. ASCO 2021. Abstr 8006. 6. Berdeja. ASCO 2021. Abstr 8008. 7. Cohen. ASH 2020. Abstr 292.

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Slide credit: clinicaloptions.com

Abstract #549

Updated Results From CARTITUDE-1: Phase 1b/2 Study of Ciltacabtagene Autoleucel, a B-cell Maturation Antigen–Directed Chimeric Antigen Receptor T Cell Therapy, in Patients With Relapsed/Refractory Multiple Myeloma

1UCSF

Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA; 2Levine Cancer Institute, Charlotte, NC, USA; 3Sarah Cannon Research Institute, Nashville, TN, USA; 4University of Chicago, Chicago, IL, USA; 5UPMC Hillman Cancer Center, Pittsburgh, PA, USA; 6Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 7Medical College of Wisconsin, Milwaukee, WI, USA; 8Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; 9Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA; 10City of Hope Comprehensive Cancer Center, Duarte, CA, USA; 11Memorial Sloan Kettering Cancer Center, New York, NY, USA; 12Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; 13Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 14University Health Network and the Princess Margaret Cancer Centre, Toronto, ON, Canada; 15Janssen R&D, Raritan, NJ, USA; 16Janssen R&D, Spring House, PA, USA; 17Janssen R&D, Beerse, Belgium; 18Legend Biotech USA, Piscataway, NJ, USA; 19Mayo Clinic, Rochester, MN, USA; 20Mount Sinai Medical Center, New York, NY, USA Presented at the 63rd American Society of Hematology (ASH) Annual Meeting & Exposition; December *Presenting author.

11-14, 2021; Atlanta, GA/Virtual.

Abstract #549: ASH Abstract and Video Summary

Additional information can be viewed by scanning the QR code or accessing this link: https://www.oncologysciencehub.com/ASH2021/ Cilta-cel/ThomasMartin The QR code is intended to provide scientific information for individual reference, and the information should not be altered or reproduced in any way.

38

Abstract #549

CARTITUDE-1: Response Data ORRa: 97.9% (95/97)

Responses deepened over time from the 1-year follow-up

100%

Best response at any time

Patients, %

80%

60%

sCR: 82.5%

sCR, % 82.5%

40%

≥VGPR: 94.9%

Median–1 year follow-up

Median–2 years follow-up

67

83

• Median time to first response was 1 month (range, 0.9–10.7) • Median time to best response was 2.6 months (range, 0.9–17.8) • Median time to CR or better was 2.9 months (range, 0.9–17.8)

20%

• Median duration of response was not estimable (21.8 months–NE)

12.4% 0%

3.1% Best responseb =

• 60.5% of patients are still progression-free at 2 years sCR

VGP R

PR 39

Abstract #549

CARTITUDE-1: Progression-Free Survival and Overall Survival Progression-Free Survival

Overall Survival

100

100 2-year PFS: 71.0% (95% CI, 57.6–80.9) Median PFS not reached (95% CI, 25.2–NE)

80

80

60

Patients (%)

Patients (%)

2-year OS: 74.0% (95% CI, 61.9–82.7) Median OS not reached (95% CI, 27.2 months–NE)

2-year PFS: 60.5% (95% CI, 48.5–70.4) Median PFS not reached (95% CI, 22.8 months–NE)

40

60

40

20

20

0

0 0

Patients at risk All patients 97 sCR patients 80

3

6

9

12

15

18

21

24

27

30

33

36

0

Months 95 80

85 78

77 73

74 71

67 64

63 61

36 35

19 19

4 4

1 1

1 1

Patients at risk All patients 97

0 0

All patients

3

6

9

12

15

18

21

24

27

30

33

36

46

23

8

2

1

0

Months 96

91

88

85

81

78

sCR patients

40

Abstract #549

CARTITUDE-1: Progression-Free Survival and Overall Survival by MRD Negativity (10-5) sustained for ≥ 6 and 12 months •

Of the 61 patients evaluable for MRD, 92% were MRD-negative (at 10-5) Progression-Free Survival 100

Overall Survival 100

2-year PFS: 100%

2-year OS: 100% 2-year OS: 100%

2-year PFS: 91.0% (95% CI, 67.1–97.8)

80

80

60

Patients (%)

Patients (%)

2-year OS: 74.0% (95% CI, 61.9–82.7) Median OS not reached (95% CI, 27.2 months–NE) 2-year PFS: 60.5% (95% CI, 48.5–70.4) Median PFS not reached (95% CI, 22.8 months–NE)

40

60

40

20

20

0

0

Patients at risk All patients MRD negativity ≥6 months MRD negativity ≥12 months

0

3

6

9

12

15

97 30 18

95 30 18

85 30 18

77 30 18

74 30 18

67 29 18

18 21 Months 63 29 18

All patients

36 17 12

24

27

30

33

36

19 12 10

4 2 1

1 1 1

1 1 1

0 0 0

Patients at risk All patients MRD negativity ≥6 months MRD negativity ≥12 months

MRD negativity sustained ≥6 months

0

3

6

9

12

15

97 30 18

96 30 18

91 30 18

88 30 18

85 30 18

81 30 18

18 21 Months 78 30 18

46 17 12

24

27

30

33

36

23 13 11

8 3 2

2 1 1

1 1 1

0 0 0

MRD negativity sustained ≥12 months 41

Advantages

BCMA Therapeutics – Advantages/Disadvantages Antibody–drug conjugate

CAR T-cells

Bispecific antibody

Off-the-shelf

Personalized

Off the shelf

Targeted cytotoxicity Not dependent on T-cell health

Targeted immuno-cytotoxicity

Targeted immuno-cytotoxicity

No lymphodepletion No steroids

Single infusion (“one and done”)

No lymphodepletion Minimal steroids

Potentially persistent

Likely available for local administration

Fact accredited center required (hospitalization likely required)

Initial hospitalization required

Currently requires REMS/Ophtho

CRS and Neurotoxicity; requires ICU and Neurology services

CRS and Neurotoxicity possible

Currently Requires dose adjustments and holds

Dependent on T-cell health (manufacturing failures)

Dependent on T-cell health (T-cell exhaustion)

Requires continuous administration

Requires significant support social – caregiver required

Requires continuous administration

Disadvantages

Available to any infusion center Outpatient administration

$$

$$$$

$$$

42

Abstract #162

Iberdomide in combination with dexamethasone in patients with relapsed/refractory multiple myeloma: results from the dose-expansion phase of the CC-220-MM-001 trial Sagar Lonial,1 Rakesh Popat,2 Cyrille Hulin,3 Sundar Jagannath,4 Albert Oriol,5 Paul G. Richardson,6 Thierry Facon,7 Katja Weisel,8 Jeremy T. Larsen,9 Monique Minnema,10 Al-Ola Abdallah,11 Ashraf Z. Badros,12 Stefan Knop,13 Edward A. Stadtmauer,14 Min Chen,15 Tuong Vi Nguyen,15 Alpesh Amin,15 Elisabeth Kueenburg,17 Teresa Peluso,16 Niels W.C.J. van de Donk18 1Winship

Cancer Institute, Emory University, Atlanta, GA, USA; 2NIHR UCLH Clinical Research Facility, University College London Hospitals NHS Foundation Trust, London, UK; 3Service d'Hématologie Hôpital Haut-Lévêque, CHU Bordeaux, Pessac, France; 4The Mount Sinai Hospital, New York, NY, USA; 5Catalan Institute of Oncology and Josep Carreras Institute, Hospital Germans Trias i Pujol, Badalona, Spain; 6Dana-Farber Cancer Institute, Boston, MA, USA; 7Service des Maladies du Sang, CHRU de Lille - Hôpital Claude Huriez, Lille, France; 8University Medical Center of Hamburg-Eppendorf, Hamburg, Germany; 9Mayo Clinic Arizona, Phoenix, AZ, USA; 10University Medical Center Utrecht, Utrecht, Netherlands; 11University of Kansas Medical Center, Kansas City, KS, USA; 12Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA; 13Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany; 14University of Pennsylvania, Philadelphia, PA, USA; 15Bristol Myers Squibb, Princeton, NJ, USA; 16Celgene International Sàrl, a Bristol-Myers Squibb Company, Boudry, Switzerland; 17Celgene International Sàrl, a Bristol-Myers Squibb Company, Boudry, Switzerland; at the time of the study; 18Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Department of Hematology, Cancer Center Amsterdam, Amsterdam, Netherlands

43 Abstract #162: ASH Abstract and Video Summary

Abstract #162

CC-220-MM-001: Response ORRa 26.2%

ORRa 25.0%

1 (0.9) 100

Response. n (%)

80

8 (7.5)

CBR 36.4%

CBR 41.7%

19 (17.8) 11 (10.3)

60

DCR 79.4%

1 (4.2) 1 (4.2)

sCR

4 (16.7)

VGPR

4 (16.7)

CR

DCR 75.0%

PR MR SD PD

40

46 (43.0)

8 (33.3)

20

4 (16.7)

15 (14.0) 0

NE

7 (6.5)

2 (8.3)

Cohort D IBER + DEX (N = 107)ᵇ

Cohort I IBER + DEX post BCMA (N = 24)ᶜ

aPR

or better; b2 patients in SD and MR discontinued treatment because of death due to COVID-19; cIncludes all treated patients who have post-baseline efficacy assessment or have discontinued treatment before any post-baseline efficacy assessment (2 patients were in C1 with no post-baseline efficacy assessments so were excluded from analysis).

C, cycle; CBR, clinical benefit rate; CR, complete response; DCR, disease control rate; MR, minimal response; NE, not evaluable; PR, partial response; sCR, stringent complete response; SD, stable disease; VGPR, very good partial response.

Lonial S, et al. ASH 2021. Abstract #162.

44

COVID-19 Status Reports  10 abstracts (including iStopMM – Abstract #154)

 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)

45

When Should Treatment Be Initiated?

Potential New Myeloma or Smoldering Myeloma

Any Myeloma Defining Events?

•CRAB •≥60% PC •FLC ≥100 •MRI >1 focal lesion

Treat as Myeloma

No Myeloma Defining Events (SMM)

High-Risk SMM (Median TTP ≈2 years)

Early Therapy With Len or Rd

Clinical Trials

Intermediate or Low-Risk SMM

Observation Rajkumar SV © 2021

46

Myeloma: Frontline Treatment Newly Diagnosed MM Not Transplant Candidate

1 - D-Rd

Transplant Candidate 1 - VRD or Dara-based quad induction 2 – VTD / VCD

2 - VRD followed by Len

(VMP-Dara; Rd)

Auto-SCT Maintenance [Len for std risk; (Len)+PI-based for high risk] Tandem for high-risk

No Delayed Transplant Outside clinical trials

P. Moreau

47

Myeloma: First Relapse First Relapse Not Refractory to Lenalidomide

1 - DRd

Alternatives including: KRd, IRd, ERd; Kd-Dara / Kd-Isa

Refractory to Lenalidomide

Kd-Dara, Kd-Isa Pom-Vd, (PomD-Dara, PD-Isa)

Dara refractory: Pd-Elo, KPd, PVd Frail: IxaPd, PCD

P. Moreau

48

Myeloma: Second or Higher Relapse First Relapse Options

• Any first relapse options that have not been tried (2 new drugs; triplet preferred) Isa-Pd, or Dara-Pd, Kd-Dara, or Kd-Isa (KPd)

Additional Options

• • • •

• • • • •

CAR T-cell Belantamab mafodotin Selinexor - dex VDT-PACE like anthracycline containing regimens Bendamustine-based regimens Elo-based regimens Panobinostat + PI Venetoclax [only t(11;14)] Cyclophosphamide-dex P. Moreau

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