IMWG Conference Series: ASH 2020

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2

Topics for Virtual Conference Series  Smoldering myeloma  Frontline therapy

 Early relapse  Key new role of immune therapies  Future directions

3

Virtual ASH 2020 Myeloma Abstracts = 688 Oral = 179 Poster = 500 (Publications only 9) Total ASH abstracts for 2020 = 4,800 (down from 6,000) 4

Smoldering Myeloma 5

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 Rajkumar SV © 2020

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 6

Risk Score to Predict Progression Risk At 2 Years Score

100 High-risk group >12

0 2 3 5

0 3 4 0 2 3 5 6 2

80

% with progression

Risk Factor FLC Ratio 0-10 (ref) > 10-25 > 25-40 > 40 M protein (g/dL) 0-1.5 (ref) > 1.5-3 >3 BMPC% 0-15 (ref) > 15-20 > 20-30 > 30-40 > 40 FISH abnormality

Intermediate-risk group (9-12)

Low-intermediate-risk Group (5-8)

60

40 Low-risk group (0-4) 20

0 0

6

12

18

24

30

36

42

48

54

60

Months

Risk Stratification Groups

Hazard Ratio (95% CI) Versus Low-risk group (censored 2 year)

0-4

Reference

5-8

7.56 (3.77 to 15.2)

9-12

17.3 (8.63 to 34.8)

> 12

31.9 (15.4 to 66.3)

Total Risk Score

2-year Progression n (%)

0-4

9 / 241 (3.7%)

5-8

67 / 264 (25.4%)

9-12

65 / 133 (48.9%)

> 12

37 / 51 (72.6%)

# at Risk

0-4

241

238

229

213

194

175

153

117

100

76

63

5-8

264

256

229

197

174

145

118

91

73

53

44

9-12

133

119

98

73

59

47

33

26

20

14

13

>12

51

41

29

21

14

9

7

5

2

2

2

San Miguel. ASCO 2019. Abstr 8000. Mateos Blood Cancer J. 2020;10:102.

7

Phase III QuiRedex with Len/Dex vs Observation: OS From Progression To Active Disease Median follow-up: 10.8 years

Len-dex, median OS: 6.4 yrs

Observation, median OS: 4.7 yrs

Early treatment does not induce more resistant relapses 8 Mateos. EHA 2020. Abstr EP950.

Abstract #57

9

Interim analysis Risk of progression to active MM according to the 2/20/20 model 1 Low-risk 1/18 (5%)

18/150 (12%)

Intermediate-risk 7/18 (39%)

High-risk 15/132 (11%)

132/150 (88%) No progression

High-risk 10/18 (56%)

Low-risk 61/132 (46%)

Progression

Intermediate-risk 55/132 (42%)

10

8/18 SMM patients with progressive disease were not high-risk according to the 2/20/20 model1 1.

Mateos MV, et al. Blood Cancer J. 2020;10(10):102.

Risk-stratification according to CTC numbers in PB Patients with >1 CTC/µL showed significantly higher risk of transformation HR: 5.1 (95% CI 2.0 – 13.4); P < .001

Time-to progression (%)

100

75

Median TTP, 6 months 50

25

0

0 Number at risk ≤1 CTC/µL 135 >1 CTC/µL 15

120

240

360

480

600

Time from study entrance (days) 65 8

33 3

13 2

6 1

0 0

11

Immune kinetics in PB from baseline until disease progression Interim analysis in patients with longitudinal samples (N = 7) NK-cell compartment

T-cell compartment

P = .034

P = .042 8

1.0

15

0.8

2 2

0.6

% cells

4

4 % cells

% cells

6

% cells

P = .026

P = .011

6

0.4

10

5

0.2

0

Baseline

Progression

0

0.0

0

Baseline

Progression

Baseline

Progression

Baseline

Progression

CD4 effector memory

CD8

T gamma-delta

Adaptive

CXCR3+, CCR4+,CCR6-

CD127+, CD28+,TIGIT+, PD1+

CD62L-, CD39-, HLADR-, CD69n, CD27-

CD39-, HLADR-,CD16TCRgd+, CD69n, CD27-

12 Significant decrease in helper effector memory CXCR3+CCR4+ and cytotoxic CD127+TIGIT+PD1+ T cells, together with a significant increase in Tγδ CD69+ T cells and adaptive NK cells

Q&A 13

Frontline Therapy 14

Myeloma: Frontline Treatment Newly Diagnosed MM Not Transplant Candidate

1 - D-Rd

Transplant Candidate

1 - VRD or Dara-based quad induction 2 â&#x20AC;&#x201C; 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 15 P. Moreau

Phase III Trials in NDMM Not Eligible for ASCT Trial

Regimen

n

mPFS

mOS

Vista1

VMP

344

24 (TTP)

56.4

FIRST2

Rd cont

535

26

59.1

SWOG7773

VRD

242* 91**

43 34

75 65

Endurance4

VRD

542 # 167 ##

34.4 37

3-year: 84% NA

Alcyone5

VMP-Dara

356

36.4

42-Mo: 75%

MAIA6

Rd-Dara

368

30-Mo: 71%

Immature

*: median age: 64; ** > 65 years; # median age 65; ## > 70 years 1. San Miguel. ASH. 2011. Abstr. 476. 2. Facon. Blood. 2018;131:301. 3. Durie. Lancet. 2017;389:519. 4. Kumar. ASCO 2020 Abstr LBA3. 5. Mateos. ASH 2019.

Abstr 859. 6. Facon. NEJM. 2019;380:2104.

16

ASH2020 – Kumar et al – MAIA Follow-up : 4 years

Median NR (55+ ?) vs 34 mos

Kumar. ASH 2020. Abstr 2276.

17

18

19

20

21

Abstract #143

22

Updated PFS (primary endpoint) Median follow up

89.8 months

Median PFS 47.3 months (Transplantation, arm B)

Median PFS 35 months (RVD alone, arm A) HR (95CI)

0.70 [0.59;0.83]

30% reduction in the risk of progression or death in patients receiving transplant

23

OS

Median follow up

89.8 months

8y-OS 62.2% (Transplantation, arm B) 8y-OS 60.2% (RVD alone, arm A)

HR (95CI)

1.03 [0.8;1.32]

More than 60% of the patients in the two arms are alive after 8 years of follow-up

24

Subgroup analyses Median follow up

89.8 months

MRD negativity rate 50 45 40

35

29.79 %

30 25

p 0.01

20.4 %

20 15

10 5 0

RVD alone

Transplant

Transplant is superior to VRD alone, even in patients who achieved undetectable MRD at 10-6 25

Q&A 26

Early Relapse 27

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)

Alternatives: KPD, PDElo Frail: Pd, IxaPd, PCD

! Challenge : patients progressing on frontline dara

28 P. Moreau

Q&A 29

Key new role of immune therapies 30

Triple-Class Refractory: When All Else Fails Monoclonal Antibodies

IMiDs / CELMoDs/ Novel Drugs

BCMA Abs

Chemotherapy

HDAC / ADC XPO inhibitors

Bispecifics/ ADCs

Cellular therapies BCMA CARs

Doxorubicin, Liposomal doxorubicin

Panobinostat/ Vorinostat

CC-220 Next Gen 38 (Iberdomide), SAR442085 CC-92480

Teclistamab AMG-701, CC-93269

Cilta-cel (JNJ-4528) Ide-cel (bb2121), Orva-cel (JCARH125)

Cyclophosphamide, Bendamustine, Melphalan

Belantamab Mafodotin

TAK-079, TAK-573, TAK-169

Venetoclax Melflufen

TNB-3838, REGN5458 PF-06863135

LCAR-B38M, bb21217, P-BCMA-101

Selinexor

MOR202, Others

BFCR4350A Talquetamab

MEDI2228, CC-99712 FOR46

Lummicar-2 (CT053) ALLO-715 ALLO-605 (TurboCAR)

PACE, HyperCAD

*Blue = approved

Green = ongoing clinical trials

31

Abstract #177

32

CARTITUDE-1: CONSORT Diagram Enrolled/apheresed, N=113 Lymphodepletion, n=101

Discontinued, n=12 Progressive disease, n=2 Withdrawal by subject, n=2 Death,a n=8

Discontinued, n=4 Withdrawal by subject, n=3 Death,a n=1

Treated with cilta-cel, n=97 Phase 1b, n=29

Phase 2, n=68 Discontinued study, n=9

Discontinued study, n=5

Death, n=9

Death, n=5

Ongoing, n=24

Ongoing, n=59

 A total of 73 patients received bridging therapy  Median turnaround timeb for cilta-cel was 29 days  No patient discontinued due to manufacturing failure aDeaths

due to progressive disease (5), acute cardio-respiratory arrest (1), sepsis (1), subdural hematoma (1), and acute respiratory failure (1; after lymphodepletion). time was defined as time from receipt to release of product.

bTurnaround

33

62nd ASH Annual Meeting 2020, Madduri D et al. PRESENTATION #177

CARTITUDE-1: ORR and MRD Assessment ORRa: 96.9% (94/97) N

Frequency in evaluable patients n=57c

Frequency in all treated n=97d

Overall MRD-

53

93.0%

54.6%

MRD- and sCR

33

57.9%

34.0%

MRD- and ≥VGPR

49

86.0%

50.5%

100%

Patients

80%

60%

sCR: 67.0%

67.0%

≥VGPR: 92.8%

 Median time to first response: 1 month (0.9–8.5)

40%

 Responses ongoing in 70 (72.2%) patients

20%

 Of evaluable patients, 93.0% achieved MRD 10-5 negativity 25.8%

0% Best responseb =

̶

4.1%

sCR

VGPR

PR

Median time to MRD 10-5 negativity: 1 month (0.8–7.7)

 Among patients with 6 months individual follow-up, most had cilta-cel CAR+ T cells below the level of quantification (2 cells/µL) in peripheral blood

34

CAR, chimeric antigen receptor; CR, complete response; MRD, minimal residual disease; ORR, overall response rate; PR, partial response; sCR, stringent complete response; VGPR, very good partial response. a PR or better, Independent Review Committee assessed. bNo patient had CR or stable disease as best response. cMRD was assessed in evaluable samples at 10 -5 threshold by next-generation sequencing (clonoSEQ, Adaptive Biotechnologies) in all treated patients at Day 28, and at 6, 12, 18, and 24 months regardless of the status of dise ase measured in blood or urine; patients were not evaluable primarily due to lack of an identifiable clone in the baseline bone marrow sample. dAll treated patients.

62nd ASH Annual Meeting 2020, Madduri D et al. PRESENTATION #177

CARTITUDE-1: Deaths N=97

Time of death post cilta-cel infusion, days

14

45â&#x20AC;&#x201C;694

5

253â&#x20AC;&#x201C;694

Pneumonia

1

109

Acute myelogenous leukemia a

2

418; 582

Sepsis and/or septic shock

2

45; 162

CRS/HLH

1

99

Lung abscess

1

119

Respiratory failure

1

121

Neurotoxicity

1

247

Total deaths during the study, n

Due to progressive disease AEs unrelated to treatment (n=3)

AEs related to treatment (n=6)

35

AE, adverse event; CRS, cytokine release syndrome; HLH, hemophagocytic lymphohistiocytosis; MDS, myelodysplastic syndrome. aOne patient with acute myelogenous leukemia had MDS and a cytogenetic profile consistent with MDS (del20q [present prior to cilta-cel infusion], loss of 5q); the other had prostate cancer and squamous cell carcinoma of the scalp.

62nd ASH Annual Meeting 2020, Madduri D et al. PRESENTATION #177

CARTITUDE-1: Conclusions  Cilta-cel has a manageable safety profile at the recommended phase 2 dose ̶

CRS was mostly grades 1/2; median time to onset of CRS was 7 days (range, 1–12) ̶

CAR-T-related neurotoxicities occurred in 20 patients (20.6%); 10.3% had grade ≥3

 Low dose of cilta-cel yielded early, deep, and durable responses in heavily pretreated relapsed/refractory MM ̶ 96.9% ORR, with sCR 67.0% ̶ Median PFS not reached; 12-month PFS rate was 76.6%, OS rate was 88.5%

 Cilta-cel is under further investigation in other populations of patients with MM in earlier-line settings ̶

Outpatient administration is being studied in CARTITUDE-2 (NCT04133636) and CARTITUDE-4 (NCT04181827)

AE, adverse event; CAR-T, chimeric antigen receptor T cell; CRS, cytokine release syndrome; MM, multiple myeloma; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; sCR, stringent complete response.

36

62nd ASH Annual Meeting 2020, Madduri D et al. PRESENTATION #177

Abstract #131

37

CRB-401

Best response 100

Patients, %

80 60 40 20 0

ORR = 100% sCR

ORR = 89.5%

CR

33.3

VGPR

31.6

PR

ORR = 50.0% ORR = 33.3% 33.3

50 50 × 106 (n = 3)

33.3

≥ CR = 38.9%

ORR = 75.8%

≥ CR = 36.8%

30.6

5.3

42.1

≥ CR = 100%

≥ CR = 38.7%

8.1

66.7 25.8

5.6

11.1

10.5

150150 × 106 (n = 18)

450450 × 106 (n = 38)

11.3

800800 × 106 (n = 3)

Total Total (N = 62)

All 15 patients with ≥ CR who had a qualified assessment were MRD negative by NGSa

aOf

24 patients with ≥ CR, 8 had no MRD assessment and 1 had an assessment outside of the 3-month window; Lin Y, et al. ASH 2020. Abstract 131.

10-4 sensitivity.

38

CRB-401

Conclusions • Updated results from CRB-401 demonstrated deep and durable responses with ide-cel in heavily pretreated patients with RRMM – Efficacy and safety reflect prior reports and support a favorable clinical benefit-risk profile for ide-cel at target dose levels ≥ 150 × 106 CAR+ T cells, with a median OS of 34.2 months in a highly triple-class– exposed population and half of ongoing responders achieving DOR > 2 years

• In the pivotal phase 2 KarMMa trial, ide-cel treatment resulted in favorable risk/benefit profile in triple-class exposed RRMM 1 – ORR 73% (including CR rate 33%)

– Median DOR 10.7 months, median PFS 8.8 months, median OS 19.4 months

• Ide-cel is also being explored in ongoing clinical trials:

KarMMa-2

Phase 2 study of ide-cel in triple-class–exposed patients and patients with high-risk MM (PD within 18 months of 1L or inadequate response to ASCT); NCT03601078

KarMMa-3

Phase 3 study of ide-cel vs standard regimens in triple-class–exposed patients with 2-4 prior lines of therapy; NCT036511282

KarMMa-4

Phase 1 study of ide-cel in patients with high-risk NDMM (R-ISS stage III disease per IMWG criteria); NCT041964913

1. Munshi NC, et al. J Clin Oncol 2020;38(suppl) [abstract 8503]; 2. Delforge M, et al. ASH 2020 [abstract 2323]; 3. Usmani SZ, et al. ASH 2020 [abstract 1418].

Lin Y, et al. ASH 2020. Abstract 131.

39

Biallelic Loss of BCMA Triggers Resistance to Anti-BCMA CAR T Cell Therapy in Multiple Myeloma Mehmet K. Samur, Mariateresa Fulciniti, Anil Aktas-Samur, Abdul Hamid Bazarbachi, YuTzu Tai, Timothy B. Campbell, Fabio Petrocca, Kristen Hege, Shari Kaiser, HervĂŠ Avet Loiseau, Kenneth Anderson and Nikhil C. Munshi 40 40

BCMA, located on 16p, was deleted

Copy Number Alterations detected by scRNAseq

Copy Number Alterations detected by WES

41

BCMA had a biallelic loss, one allele was deleted, and the second allele was mutated

% of single cells in PC cluster with CNA

~60%-70% of cells detected with BCMA stop codon mutation TP53 missense mutation was clonal

42

del16p significantly co-occurs with del17p

• del16p was observed in 4-14% of newly diagnosed patients on different datasets.

• Half of the del16p events were subclonal • Mono-allelic del16p co-occurs with del17p in 77% of the del16p patients. (6X enrichment, hypergeometric test p-value=3.38e-11) • 30-40% of patients with del17p also carried del16p.

Deletion does not effect the BCMA expression at diagnosis

• Our previous study about the chronology of CNA events showed that relative timing for del16p and del17p events were similar

43

CAR-T Discussion

44

Bi-specific Antibodies

45

Abstract #180

46

Teclistamab: Overall Response Rate ORRa for SC Cohorts

80%

 At the RP2D of 1500 µg/kg SC: 73%

60%

60%

46%

̶ ̶

Median time to first confirmed response was 1 month (0.3–3) 14/20 (70%) triple-class refractory patients responded 6/8 (75%) penta-drug refractory patients responded 15/16 (94%) responders are alive and progression-free after mF/U of 3.9 months (1.7–7.4)

n=4 n=1

n=4

40% n=3

̶

̶ ≥VGPR 55%

n=7

 Most active doses were 270–720 µg/kg IV and 720–3000b µg/kg SC ̶ ̶

20%

̶

n=5 n=3

n=4

̶

ORRa at these doses was 69% (47/68) ≥VGPR was 59%; ≥CR was 26% 67% (18/27) ORR in IV cohorts and 71% (29/41) ORR in SC cohorts 44/47 (94%) responders remain on treatment with ongoing responses after mF/U of 6.5 months (1.7–14)

0% 80 + 240 µg/kg (n=13)

PR

720 µg/kg (n=15)

VGPR

CR

1500 µg/kg (RP2D) (n=22)

 Of 11 evaluable patients across all IV and SC doses so far, 8 had MRDneg CR at 10-6 and 1 at 10-5 sensitivityc

sCR

CR, complete response; mF/U, median follow-up; MRD, minimal residual disease; ORR, overall response rate; PR, partial response; sCR, stringent complete response; VGPR, very good partial response. aAmong response-evaluable patients who had ≥1 study treatment and ≥1 postbaseline disease evaluation; includes unconfirmed responses.b4/4 patients responded at 3000 µg/kg SC dose. cPatient with MRD-neg CR at 10 -5 was indeterminate at 10 -6 due to insufficient cell counts.

47 Garfall A, et al. 62nd ASH Annual Meeting 2020. Abstract #180 Phase 1 Study of Teclistamab in RRMM

47

Teclistamab: Conclusions 

Teclistamab was well-tolerated at the RP2D of 1500 µg/kg SC



̶ Maximum tolerated dose has not been identified ̶ All CRS events were grade 1–2 and generally confined to step-up and first full doses ̶ One grade 1 reversible neurotoxicity at RP2D ̶ No new safety signals were identified High response rate observed at the RP2D ̶ ORR at the RP2D (1500 µg/kg SC) was 73%; ≥VGPR was 55% and ≥CR was 23% • 14/20 (70%) triple-class refractory patients responded; 6/8 (75%) penta-drug refractory patients responded ̶ Responses appeared durable and deepened over time ̶ At median 3.9-month follow-up, 15/16 (94%) responders are alive and progression-free



Selection of the 1500 µg/kg SC RP2D was supported by promising safety, efficacy, PK, and pharmacodynamics



Teclistamab, an off-the-shelf therapy targeting BCMA, showed promising efficacy in heavily-pretreated patients with RRMM ̶ Phase 1 of the study is ongoing, and phase 2 expansion study has started

48 Garfall A, et al. 62nd ASH Annual Meeting 2020. Abstract #180 Phase 1 Study of Teclistamab in RRMM

Abstract #290

49

GPRC5D: G Protein-Coupled Receptor Class C Group 5 Member D

 Orphan G protein-coupled receptor of unknown function Loop-3

 Limited expression in healthy human tissue, primarily in plasma cells and hair follicles1-2

Loop-1

 Highly expressed in myeloma cells and associated with poor prognostic factors in multiple myeloma (MM)1-3

Loop-4

Loop-2

 No known shed peptides or extracellular domain shedding (reduced risk for sink effect)  Ideal target for CD3 redirection

50 1Smith Sci

11(485):eaau7746. 2Pillarisetti

Blood 135(15):1232. 3Atamaniuk Eur J

Transl Med gammopathy of undetermined significance; SMM, smoldering multiple myeloma

Clin Invest 42(9):953. CD3, cluster of differentiation 3; MGUS, monoclonal

62nd

Chari et al.

ASH Meeting 2020. Abstract #290 Phase 1 Study of Talquetamab in RRMM

Talquetamab: Overall Response Rate ORRa for SC Doses 80%

73%

 At the RP2D of 405 µg/kg SC ̶

69% ORR (9/13) ̶

Median 3.7-month (1.7–6.5) follow-up for responders

̶

Median time to first confirmed response was 1 month (1–2) ̶

67% (6/9) of triple-class refractory patients responded ̶

100% (2/2) of penta-drug refractory patients responded

69% n=2

60%

50% n=1

14%

n=5

n=3

40%

20%

≥VGPR 39%

 At most active doses of 20–180 µg/kg IV and 135–800 µg/kg SC

n=3 n=4

n=3

66% ORR (33/50) ̶

≥VGPR was 42% ̶

67% ORR (12/18) in IV cohorts and 66% ORRa (21/32) in SC cohorts

n=2

̶

0% 5–45 µg/kg SC n=14

135 µg/kg SC n=8

PR a

405 µg/kg SC (RP2D) n=13

VGPR

CR

800 µg/kg SC n=11

sCR

Among response-evaluable patients who had at least 1 study treatment and 1 postbaseline disease evaluation; includes unconfirmed responses. CR, complete response; ORR, overall response rate; PR, partial response; sCR, stringent complete response, VGPR, very good partial respons e

51 62nd

Chari et al.

ASH Meeting 2020. Abstract #290 Phase 1 Study of Talquetamab in RRMM

Talquetamab: Conclusions  Talquetamab has a tolerable safety profile at the RP2D of 405 µg/kg SC Safety profile at the RP2D was generally consistent with safety at lower doses, with low incidence of infections ̶

Early DLT of Gr 3 maculopapular rash and dose reductions due to certain toxicities (skin rash, oral toxicity, back pain) were observed in 4/11 patients (36%) at 800 µg/kg SC weekly

̶

CRS was generally low grade with no grade ≥3 CRS with SC dosing Low incidence of neurotoxicity with no grade ≥3 events with SC dosing ̶

̶

 High response rate observed at the RP2D ORR was 69% (9/13) at the RP2D of 405 µg/kg SC; 39% ≥VGPR • Median time to first confirmed response was 1 month • 6/9 triple-class refractory patients responded; 2/2 penta-drug refractory patients responded Responses were durable and continued to deepen over time ̶

̶

 PK results indicate target exposure levels at the RP2D, and pharmacodynamic data demonstrate consistent T cell activation, cytokine production, and redistribution at the RP2D  SC dosing is more convenient and may offer an opportunity for less frequent dosing  Talquetamab, a first-in-class, off-the-shelf therapy targeting GPRC5D, showed encouraging efficacy in heavily-pretreated patients with RRMM ̶

Dose expansion is ongoing and phase 2 is planned

52 62nd

Chari et al.

ASH Meeting 2020. Abstract #290 Phase 1 Study of Talquetamab in RRMM

Disadvantages

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

Available to any infusion center Outpatient administration

Potentially persistent 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

Single agent activity low in CD38 refractory patients

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

$$

$$$$

$$$

53

Q&A 54

Future Directions

55

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 DPd, or DKd, or KPd

Additional Options

• Belamaf • VDT-PACE like anthracycline containing regimens • Cyclo / benda / melphalan • Panobinostat + PI • Venetoclax [only t(11;14)] • Selinexor • Melflufen • CAR-T • Bispecific 56 P. Moreau

Newer IMiDs/Cel Mods

• Iberdomide (CC-220) (Cereblon ligase modulator)

− ASH 2020 Abstract 724: First Results of Iberdomide + Dara/Dex or Iberdomide + Vd in RR MM

• CC-92480

Image: Matyskiela. J Med Chem 2018;61:535

57

Myeloma: Future State Multiple Relapse

Refractory to IMiD, PI, Anti-CD38

Refractory to IMiD, PI, Anti CD38,

Alkylators, and Anti BCMA

Anti BCMA strategy

Existing drugs: Combinations with Cyclophosphamide

BCMA ADC

Elotuzumab

(eg., Belantamab)

Selinexor

New Monoclonals

Venetoclax

Iberdomide, CC-94480

Bispecific

Panobinostat

New ADCs

Anti BCMA

Bendamustine

New bi-specifics

VDT PACE

New CAR-Ts

that do not have IMiD, PI, Anti CD38

BCMA CAR-Ts Rajkumar SV © 2020

New Drugs:

58

Q&A 59

Replay available: https://www.myeloma.org/videos/ imwg-conference-series-ash-2020

60

Thank you to our sponsors!

61