1 of 31

Understanding and Managing Immune Effector Therapy in Multiple Myeloma: When You CART or BiTE

Saad Z. Usmani, MD MBA FACP FRCP FASCO

Chief of Myeloma Service, MSKCC

Professor, Weill Cornell Medical College, Cornell University

2 of 31

Disclosures

  • Research funding: Amgen, Array Biopharma, BMS, Celgene, GSK, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, SkylineDX, Takeda.
  • Consulting: Abbvie, Amgen, BMS, Celgene, EdoPharma, Genentech, Gilead, GSK, Janssen, Oncopeptides, Sanofi, Seattle Genetics, SecuraBio, SkylineDX, Takeda, TeneoBio.

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

3 of 31

This is the age of immune therapy in MM therapeutics – our collective aim is cure.

Adapted from Cho S-F et al. Front Immunol. 2018;9:1821.

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

4 of 31

Bispecific Antibodies (BsAbs) – Many Different Platforms

Adapted from Lejeune M et al. Front Immunol 2020 11:762.

Bispecific T-cell Engager or BiTE (Amgen)

Dual Affinity Re-Targeting or DART

(Janssen, Macrogenics)

Tandem diabodies or TandAb (Affimed)

BsAb armed activated T-cells or BAT (mostly academic)

T-cell dependent BsAb Xmab (Xencor, Glenmark, Amgen)

CrossMAb

(Celgene, Roche)

Duobody (Genmab)

Trifunctional Antibody or TriFAb

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

5 of 31

Clinical Trail Data in Multiple Myeloma

6 of 31

Teclistamab – 1st EMA/FDA Approved BsAb for MM

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

7 of 31

Summary of BCMA Bispecific Antibodies

Teclistamab

(n=165)

Linvoseltamab

(n=167)

ABBV-383

(n=118)

Elranatamab

(n=123)

Alnuctamab

(n=68)

Route

SC

IV

IV

SC

SC

Dose and schedule

1.5mg/kg/QW

Q1W x 16w

W≥16: Q2W

Q3W

76mg/Q1W

C≥7: Q2W if PR

Q1W x 8 w

Q2W C3-C7

C≥7 Q4W

Median prior LoT

5 (2-14)

6 (2-17)

5 (1-15)

5 (2-12)

4 (3-11)

Triple refractory

77.6%

90%

61%

96%

63%

CRS, G≥3

72.1%, 0.6%

47.9%, 0.6%

54%, 3%

57.7%, 0%

53%, 0%

Neurotoxicity, G≥3

3%, 0

4%, 0

NR, 6 pts

4, 3.4

2 pts, 3%

Infections, G≥3

76.4%, 44.8%

NR

32%, 17%

66.7%, 35%

34%, 9%

ORR (%)

63%

75%

200-800 mg

60%/81%* *at ≥40 mg

61%

53%

≥CR (%)

39.4%

16%

20%/30%*

27.6%

23%

Median PFS (m)

(95% CI)

11.3 m

(8.8-17.1)

Not reported

Not reported

NE

(10.4-NE)

Not reported

Median DoR (m)

(95% CI)

18.4 m

(14.9-NE)

Not reached

Not reported

NE

(12.0-NE)

Not reported

MRD – (10-5)

26.7%

4/10

Not reported

90.9% (n=22)

16/20

FDA APPROVED

X

X

Moreau P et al. NEJM 2022; Bahlis N et al. ASH 2022; Wong S et al. ASH 2022; Voorhees PM et al. ASH 2022 ;

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

8 of 31

Summary of non-BCMA Bispecific Antibodies

Chari A et al. NEJM 2023; Carlo-Stella et al. ASH 2022; Trudel S et al. ASH 2021.

Talquetamab

(n=288)

Forimtamig

(n=57 )

Cevostamab

(n=157)

Target

GPRC5d-CD3

2+1 GPRC5d-CD3

FcRH5-CD3

Route

SC (n=143)

SC (N=145)

SC

IV

Dose and schedule

0.4 mg/kg QW

0.8mg/kg Q2W

1200-7200 mcg/kg

Q2W

Q3W

Median prior LoT

5 (2-13)

5 (2-17)

4 (2-14)

6 (2-18)

Triple refractory

74.1%

69%

71.9%

85%

CRS, G≥3

79%, 2.1%

72.4%, 0.7%

78.9%, 1.8%

81%, 1.2%

Neurotoxicity, G≥3

13.9%, 1.6%

10%, 1.8%

12.3%, .6%

14.3%, 0.6%

Infections, G≥3

57.3%, 16.8%-

50.3%, 11.7%

45.6%, 26.4%

45%, ND

ORR (%)

74.1%

73.1%

63.6%

56.7%

132-198mg

≥CR (%)

33.6%

32.4%

25.5%

8.4%

Median PFS (m)

(95% CI)

7.5

(5.7-9.4)

11.9

(8.4-NE)

NR

NR

Median DoR (m)

(95% CI)

9.3

(6.6-12.7)

13.0

(10.6-NE)

12.5

(1.2-12.5)

11.5

(6-18.4)

MRD – (10-5)

NR

NR

10/14

7/10

FDA APPROVED

X

X

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

9 of 31

Summary of Bispecific Antibodies - Infections

 

Teclistamab

n=165

Elranatamab

n=123

Alnuctamab

n=68 (sc)

ABBV-838

n=118

Talquetamab

n=288

[0.4-0.8mg/kg]*

Cevostamab

n=161

Forimtamig

n=57 (SC)

Median FUP (months, m)

14.1 m

10.4 m

4.1 m

4.3 – 8.0m

14.9 – 8.6 m

8.8 m

8.0m

Overall, n (%)

126 (76.4)

82 (66.7)

23 (34)

38 (32)

57.3%-50.3%

45%

26 (45.6)

Grade 3-4, n (%)

74 (44.8)

43 (35)

6 (9)

20 (17)

16.8%-11.7%

ND

15 (26.4)

Bacterial

ND

ND

ND

ND

 

ND

ND

Fungal

ND

ND

ND

ND

 

ND

ND

Viral

ND

ND

ND

ND

 

ND

ND

Opportunistic infections

  1. PJP
  2. CMV

 

6 patients

NR

(*1 patients with Adenoviral pneumonia)

 

6 (4.9)

10 (8.1)

 

ND

ND

 

ND

ND

 

 

5(3.5%)–4(2.8%)

ND

3 patients

ND

ND

COVID infections, n (%)

Overall

Grade 3-4

 

29 (17.6)

20 (12.1)

 

31 (25.2)

14 (11.4)

 

ND

ND

 

ND

ND

 

13(9.1) – 16(11)

0.7% - 2.1%

ND

 

12 (24.6)

2 (3.6)

Infectious death, n (%)

16/27

NR

ND

4 pts

NR

ND

ND

Moreau P et al. NEJM 2022; Lesokhin A et al. ASH 2022. ; Wong S et al. ASH 2022; Voorhees PM et al. ASH 2022; Chari A et al. NEJM 2023; Carlo-Stella et al. ASH 2022; Trudel S et al. ASH 2021

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

10 of 31

Teclistamab: Long-term Follow-up from MajesTEC-1

van de Donk NWCJ et al. ASCO 2023; Usmani SZ et al ASCO 2023.

165 pts, median f/u 2 years

  • Median prior LOT, 5
  • ORR, 63.0%
  • ≥ CR, 45.5%
  • 81% of MRD evaluable pts were MRD undetectable at Day 100
  • ORR for pts with 3 vs > 3 prior LOT, 74.4% vs 59%

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

11 of 31

Mechanisms of resistance to BsAbs

Adapted from: van de Donk N, Themeli M, Usmani SZ. Blood Cancer Discov 2021;2:302–18

T-cell characteristics

  • T-cell frequency
  • T-cell fitness

MM microenvironment-related factors

  • BM stromal cells
  • Immune suppressor cells

BsAb characteristics

  • Affinity for target
  • Dose
  • Immunogenicity
  • Dual targeting

Tumor-related features

  • Antigen loss or diminished antigen expression
  • Soluble BCMA (for BCMA BsAbs)
  • Tumor load
  • High-risk cytogenetic features
  • Extramedullary disease
  • Inhibitory receptors and ligands, �which suppress T-cell function

IMiD/CelMOD,

Check point

inhibitors

CD38 antibody: Elimination of Tregs

BCMA, B-cell maturation antigen; BM, bone marrow; BsAb, bispecific antibody; IMiD, immunomodulatory drug; MMC, multiple myeloma cell; Tregs, regulatory T-cells

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

12 of 31

TRIMM-2: Talquetamab and daratumumab

CR, complete response; CRS, cytokine release syndrome; dara, daratumumab; ICANS, immune effector cell-associated neurotoxicity syndrome; mAb, monoclonal antibody; ORR, overall response rate; PL, prior lines of treatment; PR, partial response; QW/Q2W, weekly/every 2 weeks; SC, subcutaneous; sCR, stringent CR; SD, stable disease; Tal, talquetamab; VGPR, very good partial response

van de Donk N et al. EHA 2022;abstract S183 (oral presentation)

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

aIncluding a PI and an IMiD. b1–3 step-up doses given within 1 week before a full dose.

cGlucocorticoid, antihistamine, and antipyretic.

Parameter

Evaluable

patientsa

Tal 400 μg/kg QW

+ dara (n=14)

Tal 800 μg/kg Q2W

+ dara (n=37)

Follow-up, median (range)

6.7 months

(1.9–19.6)

4.2 months

(0.2–12.3)

ORRb, n (%)

10 (71.4)

31 (83.8)

CR/sCR

4 (28.6)

11 (29.7)

VGPR

4 (28.6)

13 (35.1)

PR

2 (14.3)

7 (18.9)

SD

4 (28.6)

4 (10.8)

PD

0

2 (5.4)

Time to first confirmed response, median (range)

1.0 month

(0.9–2.4)

1.0 month

(0.9–6.5)

aResponse-evaluable patients had received ≥1 study treatment and had ≥1 postbaseline response evaluation by the investigator. bPR or better in response-evaluable patients; includes unconfirmed responses.

  • Median age, years: 400 µg/Kg 68 (50-77); 800 µg/Kg 62 (44-81)
  • Median PL: 6; 5
  • High-risk cytogenetics: 1 (10.0%); 5 (19.2%)
  • Triple-class refractory: 8 (57.1%); 28 (63.6%)
  • Anti-CD38 mAb refractory: 11 (78.6%); 33 (75.0%)
  • Median follow-up 5.1 months
  • CRS all grades: 10 (71.4%); 34 (77.3%); Grade 3/4 0; 0
  • ICANS: 2 patients, both grade 1 and resolved within 1 day
  • Dysgeusia, all grades: 10 (71.4%), grade 3/4 NA; 26 (59.1%), grade 3/4 NA. Dry mouth, all grades: 10 (71.4%), grade 3/4

0; 18 (40.9%), grade 3/4 0

  • 31 patients (53.4%) had infections (grade ≥3: 17.2%)
  • Skin- and/or nail-related AEs: 81.0 % (47/58) patients

13 of 31

Phase 1b RedirecTT-1: Teclistamab + Talquetamab

Cohen YC et al. ASCO 2023. Abstract 8002.

Mateos M-V et al. EHA 2023. Abstract S190.

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

14 of 31

RedirecTT-1: Conclusions

Cohen YC et al. ASCO 2023. Abstract 8002.

Mateos M-V et al. EHA 2023. Abstract S190.

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

15 of 31

Pros/Cons of Bispecifics

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

    • Off the shelf
    • Low grade cytokine release syndrome (CRS)
    • Low incidence of neurotoxicity (NT)
    • Ability to combine with other mechanisms of actions

Pros:

    • Not every patient is responding to BsAbs.
    • Continuous therapy model associated with infection risk
      • Hypogammaglobulinemia requiring IVIg administration
      • VZV/PJP Prophylaxis
    • Logistic challenges for community at large during first cycle of monitoring and managing CRS/NT

Cons:

16 of 31

Hot off the press…April 30, 2024.

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

17 of 31

BCMA-Targeted CAR T-Cell Therapies Indicated for MM

BCMA, B-cell maturation antigen; CAR, chimeric antigen receptor; MM, multiple myeloma; R/R, relapsed/refractory.

BCMA-Targeted Therapy

Indications

Idecabtagene vicleucel

  • Adults with R/R multiple myeloma after > 2 prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody (April 4, 2024)
  • Adults with R/R multiple myeloma after ≥4 prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody

Ciltacabtagene autoleucel

  • Adults with relapsed and lenalidomide-refractory multiple myeloma after > 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent (April 5, 2024)
  • Adults with R/R multiple myeloma after ≥4 prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

18 of 31

KarMMa-3: Randomized Trial Ide-Cel vs SOC

Rodriguez-Otero P, et al. N Engl J Med. 2023;388(11):1002-1014.

14.8 months

9.7 months

Ide-cel

SOC

1.0

0.7

0.5

0.3

0.2

0.0

0.1

0.4

0.6

0.8

0.9

Probability of PFS

0

12

15

30

6

3

9

33

18

21

24

27

Months since randomization

254

206

178

149

110

62

40

22

14

4

2

0

132

75

42

32

25

13

10

7

6

2

1

0

Ode-cel

Standard regimen

No. at risk

0.73

0.40

0.55

0.30

Ide-cel

Standard of care

SOC regimens (n = 132):

43 Dara-Pd

30 Kd

30 Elo-Pd

22 Ixa-Rd

7 Dara-Vd

**93% were refractory to dara

Ide-cel

(n = 225)

SOC

(n = 126)

Median lines of therapy

3

3

Extramedullary disease

24%

24%

HR cytogenetics

42%

46%

Triple-class refractory

65%

67%

Penta-refractory

6%

4%

Median dose of ide-cel:

445 x 106 CAR+ T cells

Duration of Response

Progression-Free Survival

(Intent-to-treat population)

Ide-cel

Standard regimen

Median PFS, months (95% CI)

13.3 (11.8−16.1)

4.4

(3.4−5.9)

HR (95% CI)

0.49 (0.38−0.65)

P value

<0.001

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

19 of 31

CARTITUDE-4: Phase 3 Cilta-Cel vs SOC (DPd or VPd)

San-Miguel J, et al. N Engl J Med. 2023;389(4):335-347

Median follow-up 15.9 months

Cilta-cel

(n = 208)

SOC

(n = 211)

Median lines of therapy

2 (1–3)

2 (1–3)

Extramedullary disease

21%

17%

HR cytogenetics

59%

63%

Triple-class refractory

25.5%

26.1%

Penta-exposed

6.7%

4.7%

ORR

ITT: 84.6%

As-tx: 99.4%

67.3%

MRD-neg (10-5)

ITT: 61%

As-tx: 72%

16%

12-month DOR

84.7

63.0%

Cilta-cel was associated with superior PFS in the ITT population; patients in cilta-cel arm received DVd or VPd bridging, but had higher number of early progressions vs SOC

100

80

60

40

20

0

10

30

50

70

90

Percentage of patients surviving without disease progression

Months

Wk 8

0

3

6

9

12

15

18

21

24

27

30

Cilta-cel group

Standard-care group

No. at risk

Cilta-cel group

Standard-care group

208

211

166

116

45

20

1

0

9�1

22

4

94

46

146

88

172

133

177

176

0

0

HR* 0.40 (0.29–0.55); P < 0.0001

PFS: ITT Population

*unweighted

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

20 of 31

Why Use CART Early?

Derman B, et al. Blood Adv. 2023;7(19):5703-5712. Song Y, et al. ASH. 2023;Abstract 1009. Mateos M-V, et al. J Clin Oncol. 2024;42(suppl 36):Abstract 439572.

  • Anti-CD38 mAb increasingly being used in frontline, and anti-CD38 mAb + R as maintenance
  • At first relapse, patients may have anti-CD38 mAb and IMiD resistance
  • What are the options?

Belantamab mafodotin + Vd in 2L+ had median PFS of 36.6 months

0

21

3

6

9

12

15

18

24

36

33

30

27

39

42

0.0

1.0

0.6

0.4

0.2

0.8

PFS (probability)

Time since randomization (months)

BVd

DVd

43%

69%

18 months

Median �13.4 months

Median �36.6 months

PFS

BVd �(n = 243)

DVd �(n = 251)

HR �(95% CI)

P-value

Events, n (%)

91 (37)

158 (63)

mPFS

(95% CI), mo

36.6�(28.4-NR)

13.4�(11.1-17.5)

0.41 �(0.31-0.53)

< 0.00001

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

21 of 31

Why Use CART Early?

Derman B, et al. Blood Adv. 2023;7(19):5703-5712. Song Y, et al. ASH. 2023;Abstract 1009.

CARTITUDE-4 PFS

Appropriate for second-line CAR T

Later CAR T may be appropriate

Triple-class refractory disease at first relapse

No anti-CD38 mAb resistance (anti-CD38 mAb)

Value extended treatment-free period

Value weekly visits > hospitalization

Place premium on efficacy > toxicity

Place premium on lower toxicity

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

22 of 31

Cytopenias After BCMA-Targeting CAR T

Logue J, et al, Blood Adv. 2022;6(24):6109-6119. Thibaud S, et al. Blood. 2022;140(Suppl1):614-616.

  • Occur in almost all patients who received ide-cel (91%) and cilta-cel (100%)
  • Median time to recovery, ≥ 3 months
  • Commonly results in infections

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

23 of 31

Comparison of infectious complications with BCMA-directed therapies – the MSKCC Experience

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

Nath K et al. Blood Cancer J 2024;14(1):88.

Estimated cumulative incidence of grade ≥3 infections over time

24 of 31

Secondary (Hematologic) Cancers Post-CAR T-Cell Therapy

Rodriguez-Otero P, et al. New Engl J Med. 2023; 388(11):1002-1014. Lin Y, et al. J Clin Oncol. 2023;41(16):Poster 8009. San-Miguel J, et al. New Engl J Med. 2023;389(4):335-347.

Trial

Secondary hematologic malignancy incidence

Ide-cel (KarMMa-3) vs SOC

2% vs 0% [all MDS/AML]

Cilta-cel (CARTITUDE-1)

10% [Mostly AML/MDS, 1 B-cell lymphoma]

Cilta-cel (CARTITUDE-4) vs SOC

3% vs 0% [2% AML/MDS, 1% TCL]

Use of fludarabine/cyclophosphamide + risk of insertional mutagenesis raises specter of second hematologic cancers

Retrospective analyses

Details

FDA

33 cases of T-cell lymphoma among ~30K cases

Ghilardi G,et al.

Nat Med. 2024;30(4):984-989

Case of TCL after CD19 CAR T;

clone identified before CAR T infusion

Harrison S, et al.

Blood. 2023;142(Suppl1):6939

TCL after cilta-cel;

possibly driven by clone present before CAR T

Elsallab M, et al.

Blood. 2024;143(20):2099-2105

FAERS database; Myeloid leukemias and T-cell lymphomas reported [estimated 0.1% incidence]

AML, acute myeloid leukemia; MDS, myelodysplastic syndrome, TCL, T-cell lymphoma

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

25 of 31

Secondary (Hematologic) Cancers Post-CAR T-Cell Therapy

Black Box Warning:

Secondary hematological malignancies, including MDS, AML, T-cell malignancies

Longer follow-up from randomized trials of CAR T versus SOC should help to clarify the excess risk of secondary blood cancers

  • Many factors make it hard to conclude if there are associations between CAR T therapy and secondary cancers
    • Most patients received melphalan and lenalidomide in the past and there is a latency to developing secondary cancers from these drugs
    • Unclear if CAR transgene is present in T-cell lymphomas
    • Unclear if clones were present before CAR T-cell therapy
    • Unclear denominator in these analyses

IS THERE A LINK?

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

26 of 31

Real World Ide-Cel

SOC, standard of care

Hansen DK, et al. J Clin Oncol. 2023;41(11):2087-2097.

10% underwent apharesis but never received their product

(KarMMA, 9%; KarMMA-3: 7.5%)

Leukapheresis for planned SOC ide-cel CAR T therapy

(N = 196)

Did not proceed to CAR T infusion (n = 17)

  • Manufacturing failure (n = 5)
  • Progression/death (n = 12)

Pending ide-cel CAR T therapy infusion (n = 20)

Ide-cel infusion (n = 159)

  • SOC ide-cel (n = 158)
  • Expanded access program (n = 1)

Patients who are not infused were not included in initial outcomes analyses, which may inflate

PFS, OS, etc

27 of 31

Real World Ide-Cel

Compared to KarMMA:

  • ORR similar
  • PFS similar
  • OS worse (12.5 vs 19.4 months)

Hansen DK, et al. J Clin Oncol. 2023;41(11):2087-2097.

Day 30 (n = 159)

Day 90 (n = 149)

Best ORR (n = 159)

0

25

50

75

100

Percent

CR or sCR: 30%

ORR: �78%

CR or sCR: 38%

CR or sCR: 42%

ORR:�84%

ORR: �72%

CR or sCR, MRD+

VGPR

PR

CR or sCR, MRD-

CR or sCR, MRD unknown

0

12

3

6

9

0.75

0.50

0.25

1.00

PFS (probability)

Months

No. at risk

All

159

21

0

115

68

All

Median PFS, 8.5 months

95% CI, 6.5 to NR

0

12

3

6

9

0.75

0.50

0.25

1.00

OS (probability)

Months

No. at risk

All

159

37

2

138

93

All

Median OS, 12.5 months

95% CI, 11.3 to NR

Best Overall Tumor Responses

PFS From Ide-Cel Infusion

OS From Ide-Cel Infusion

28 of 31

Real-World Cilta-Cel

Hansen DK, et al. J Clin Oncol. 2023;41(suppl16):8012.

Real-world pts, retrospective

N = 139

Median age, years

64 (30–79)

ECOG PS 0 or 1

89%

High-risk Disease Features

Extramedullary disease

High-risk cytogenetics

Plasma cell leukemia

Prior BCMA therapy

ISS-3/R-ISS 3

31%

41%

7%

12%

22%

Penta-refractory disease

34%

Bridging Therapy

80%

Out of specification

22%

Grade >3 CRS and ICANS

5% / 6%

Delayed neurotoxicity

Parkinsonism

Bell’s/CN palsy

12%

1%

6%

*57% ineligible for CARTITUDE-1*

High-risk cytogenetics associated with inferior ORR, PFS, OS

Best ORR

ITT Best ORR

CR or sCR: 56%

ORR: �89%

CR or sCR: 53%

ORR: �84%

CR or sCR, MRD+

VGPR

PR

CR or sCR, MRD-

CR or sCR, MRD unknown

Real-World PFS

Real-World OS

0

12

3

6

9

0.75

0.50

0.25

1.00

0.00

PFS (probability)

Months

All

12-month PFS estimate: 67%

95% CI: 55-80%

No. at risk

All

159

56

8

141

119

0

12

3

6

9

0.75

0.50

0.25

1.00

0.00

OS (probability)

Months

All

12-month OS estimate: 79%

95% CI: 72-87%

No. at risk

All

153

60

9

145

123

29 of 31

Factors Associated With Outcomes in BCMA-Directed �CAR T-Cell Therapy

Criterion

Ide-Cel

Cilta-Cel

Source(s)

Association with response

Association with PFS/OS

Association with response

Association with PFS/OS

Higher ISS stage

Negative

Negative

Negative

Negative

Rodriguez-Otero, et al. Hemasphere. 2022; Rodriguez-Otero, et al. NEJM. 2023; Munshi, et al. NEJM. 2021; Martin, et al. JCO. 2022.

High-risk cytogenetics

Negative

Negative

Negative

Negative

Gagelmann, et al. Haematologica. 2023; Gagelmann, et al. JCO. 2024; Munshi, et al. NEJM. 2021; Martin, et al. JCO. 2022, Hashmi, et al. Haematologica. 2023; Hansen, et al. ASCO. 2023

Extramedullary disease

Negative 

Negative

 Negative 

Negative

Ibid

Plasma cell leukemia

Negative

Negative

Negative

Negative

Ibid

High/rapidly increasing disease burden

Negative?

Negative?

Negative?

Negative?

Rodriguez-Otero, et al. Hemasphere. 2022; Rodriguez-Otero, et al. NEJM. 2023; Martin, et al. JCO. 2022

Prior BCMA-directed therapy

- Antibody-drug conjugate

- Bispecific antibody

- CAR T-cell therapy (same product)

- CAR T-cell therapy (diff product)

 

Negative

Negative

Negative

None

Negative

Negative

Negative

None

 

Negative

Negative

Negative

Unknown

Negative

Negative

Negative

Unknown

Cohen, et al. Blood. 2022; Ferreri, et al. BCJ. 2023; Hashmi, et al. Haematologica. 2023; Munshi, et al. NEJM. 2021; Martin, et al. JCO. 2022

Patient-Related Factors

ECOG Performance Status ≥ 2

Negative 

Negative

 Negative 

Negative

Hansen, et al. JCO. 2023

Ferritin > upper limit of normal

Negative

Negative

Negative

Negative

Hashmi, et al. Haematological. 2023; Gagelmann, et al. JCO. 2024;

30 of 31

Conclusions

  • The myeloma treatment landscape is now undergoing a paradigm shift with novel immunotherapies extending our patient’s lives.
  • BCMA-/GPRC5D-directed therapies are available for TCR/penta-refractory disease.
  • Early use of CART makes sense, especially for anti-CD38/IMiD exposed or refractory pts.
  • Access (and equity) will be a key, issue with CAR T but improving.
    • BCMA BsAb appears to be an effective off the shelf option!
    • Logistics will differ for academic versus community settings.
  • Figuring out how to combine/sequence bispecific antibodies safely and effectively is the next hurdle.

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

31 of 31

MSKCC Myeloma Team – It Takes a Village!

Physicians:

  • Parastoo Dahi (ABMT)
  • Sergio Giralt (Deputy Chair, DHM)
  • Alexander Lesokhin
  • Hani Hassoun
  • Malin Hultcrantz
  • Neha Korde (Clinical Director)
  • Heather Landau (ABMT)
  • Kylee Maclachlan
  • Sham Mailankody (Research Director)
  • Francesco Maura
  • Dhwani Patel
  • Sridevi Rajeeve
  • Michael Scordo (ABMT)
  • Gunjan Shah (ABMT)
  • Urvi Shah
  • Carlyn Tan
  • Saad Z. Usmani (Chief)

APPs:

  • Isabel Concepcion
  • Katie Jones
  • Justina Kiernan (BER)
  • Lori Lang (WES)
  • Katelyn Kelly-Johnson (CMK)
  • Jennifer Rielly
  • Ashley Steinberger
  • Jenna Wenzel

CTNs:

  • Marcela Algave, RN
  • Kelly Barnett, RN
  • Jenna Blaslov, RN
  • Julia Caple, RN
  • Tara Sood, RN
  • Ling Tran, RN

OPNs:

  • Kelly Aliaga
  • Grismer Canales
  • Carolanne Carini (BER)
  • Kathleen Considine (WES)
  • Alexa Cracolici (MON)
  • Kellie Donovan
  • Mackenzie Galvin
  • Anna Howard
  • Kyla Lafond
  • Michelle O’Hare (CMK)
  • Pattie Scherer (BER)

PharmDs:

  • Alice Wang
  • Issam Hamadeh

Clinical Research Team:

  • Miranda Burge
  • Leah Gilbert
  • Bianca Gonzalez
  • Laura Guttentag (CRM, Myeloma)
  • Selena Hamid
  • Roger Huang
  • Meredith Hyland
  • Mosammed Kabir
  • Emily Lei
  • Guljar Nahar
  • Alexis Nwakwo
  • Garrett Preusz
  • Anna Przemielewska
  • Raisa Rahman
  • Colin Rueda
  • Jeannen Santos
  • Tala Shekarkhand
  • Felicia Slaton
  • Clare Sullivan
  • Kristina Vinzon-Baltazar

OCs:

  • Fariha Ali
  • Xavier Ayala
  • Elhaji Ba
  • Ruth Bien-aime
  • Odali Espinal
  • Eric Frazer
  • Daniel Maldonado
  • Krystal Soto

Service Manager/Admins:

  • Malika Langaine
  • Chelsea Brooklyn
  • Shaneeza Imran
  • Gladys Acosta