Promising therapeutic approaches for relapsed/refractory multiple myeloma

Figures & data

Table 1. Clinical trials with different drug modalities in the RRMM setting.

Drug categories	Product name	Development phase	Study no.	study participants	Key efficacy	Key safety	Ref
Anti-BCMA CAR T-cell therapy	bb2121 (Idecabtagene vicleucel)	Phase 2, KarMMa study	NCT03361748	128	ORR was 73%, CR was 33%, VGPR was 52%, The mediam PFS time was 8.8 months. OS time was 19.4 months.	CRS was 84%, neutropenia (91%), anemia (70%), and thrombocytopenia (63%).	[21]
	bb21217	Phase 1, CRB-402 study	NCT03274219	72	ORR was 69%, CR was 36%, The median DOR was 23.8.	CRS was 75%, 15% patients developed neurotoxicity.	[23]
	Ciltacabtagene autoleucel (LCAR−B38M)	Phase 1/2, LEGEND-2 study	NCT03090659	57	ORR wasv88%, CR was 74%, VGPR was 4%, PR was 11%, The median PFS time was 20 months.	–	[26]
	Ciltacabtagene autoleucel (JNJ-4528)	Phase 1b/2, CARTITUDE-1 study	NCT03548207	97	ORR was 97%, sCR was 67%, VGPR was 32.0%, PR was 7.2%. Overall 12 month PFS and OS rates were 77% and 89%, respectively.	CRS was 95%, neutropenia (90.7%), anemia (81.4%), and thrombocytopenia (79.4%).	[28]
Combined CAR T-cell therapy	Unnamed	Phase 1	ChiCTR-OIC-17011272	21	ORR was 95%, sCR was 43%, CR was 14%, VGPR was 24%, PR was 14%.	CRS was 90%.	[31]
	Unnamed	Phase 1	ChiCTR1800018143	16	ORR was 87.5%, sCR was 50%, VGPR was 12.5%, PR was 25%, 75% with PFS at 9 months.	–	[32]
Antibody-drug conjugates	Belantamab mafodotin (GSK2857916)	Phase 2, DREAMM-2 study	NCT 03525678	196	ORR was 34% (2·5 mg/kg cohort), ORR was 30% (3·4 mg/kg cohort), The DOR in the two groups was 11.0 and 13.1 months, and the median PFS was 2.9 and 2.2 months, respectively.	Keratopathy (33%, 27%), thrombocytopenia (17%, 20%), anemia (11%, 31%), and decreased lymphocyte count (11%, 14%).	[35]
Bispecific Ab therapy	AMG 420	Phase1b	NCT02514239	42	ORR was 70%, sCR was 11%.	CRS was 61%, anemia (43%), neutropenia (23%), and thrombocytopenia (20%).	[39]
	AMG 701	Phase 1, FIH study	NCT03287908	75	ORR was 36%, The median time to response was 1.0 month.	–	[40]
	CC-93269	Phase1	NCT03486067	175	ORR was 43.3% and the CR/sCR was 16.7%.	CRS was 76.7%, infections was 56.7%.	[41]
	Talquetamab (JNJ-64407564)	Phase1	NCT03399799	174	ORR was 78% (IV), and was 67% (SC).	Anemia (50%), CRS (47%), neutropenia (45%), and lymphopenia (40%).	[44,45]
CELMoDs	Iberdomide (CC-220)	Phase 1/2	NCT02773030	107	ORR was 35% (IberDd cohort) and 50% (IberVd cohort), the median response time was 4.1 and 4.9 weeks.	Neutropenia (45%), leukopenia (20.6%), and anemia (28%)	[48]
	CC-92480	Phase1	NCT03374085	76	The ORR was 21.1%, with 1 CR, 6 VGPRs, 9 PRs, and 4 MRDs.	Myelosuppression	[50]

Abbreviations: BCMA: B cell maturation antigen, CAR: chimeric antigen receptor, ORR: overall response rate, CR: complete response, PFS: progression free survival, VGPR: very good partial response, CRS: cytokine release syndrome, PR: partial response, sCR: stringent complete response, IV: intravenous, SC: subcutaneous, MRD: measurable residual disease, RRMM: relapsed/refractory multiple myeloma.

Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384(8):705–716.

 PubMed Web of Science ®Google Scholar

Raje NS, Jagannath S, Kaufman JL, et al. Updated clinical and correlative results from the phase I CRB-402 study of the BCMA-targeted CAR T cell therapy bb21217 in patients with relapsed and refractory multiple myeloma. Blood. 2021;138(Suppl 1):548.

 Google Scholar

Madduri D, Usmani SZ, Jagannath S, et al. Results from CARTITUDE-1: a phase 1b/2 study of JNJ-4528, a CAR-T cell therapy directed against B-cell maturation antigen (BCMA), in patients with relapsed and/or refractory multiple myeloma (R/R MM). Blood. 2019;134(Suppl_1):577.

 PubMedGoogle Scholar

Berdeja JG, Madduri D, Usmani SZ, et al. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet. 2021;398(10297):314–324.

 PubMed Web of Science ®Google Scholar

Yan Z, Cao J, Cheng H, et al. A combination of humanised anti-CD19 and anti-BCMA CAR T cells in patients with relapsed or refractory multiple myeloma: a single-arm, phase 2 trial. Lancet Haematol. 2019;6(10):e521–e529. DOI:10.1016/S2352-3026(19)30115-2.

 PubMed Web of Science ®Google Scholar

Li C, Mei H, Hu Y, et al. A bispecific CAR-T cell therapy targeting BCMA and CD38 for relapsed/refractory multiple myeloma: updated results from a phase 1 dose-climbing trial. Blood. 2019;134(Suppl_1):930.

 Google Scholar

Richardson PG, Lee HC, Abdallah AO, et al. Single-agent belantamab mafodotin for relapsed/refractory multiple myeloma: analysis of the lyophilised presentation cohort from the pivotal DREAMM-2 study. Blood Cancer J. 2020;10(10):106.

 PubMed Web of Science ®Google Scholar

Topp MS, Duell J, Zugmaier G, et al. Anti-B-cell maturation antigen BiTE molecule AMG 420 induces responses in multiple myeloma. J Clin Oncol. 2020;38(8):775–783.

 PubMed Web of Science ®Google Scholar

Harrison SJ, Minnema MC, Lee HC, et al. A phase 1 first in human (FIH) study of AMG 701, an anti-B-cell maturation antigen (BCMA) half-life extended (HLE) BiTE® (bispecific T-cell engager) molecule, in relapsed/refractory (RR) multiple myeloma (MM). Blood. 2020;136(Suppl 1):28–29.

 Google Scholar

Costa LJ, Wong SW, Bermúdez A, et al. First clinical study of the B-cell maturation antigen (BCMA) 2 + 1T cell engager (TCE) CC-93269 in patients (Pts) with relapsed/refractory multiple myeloma (RRMM): interim results of a phase 1 multicenter trial. Blood. 2019;134(Suppl_1):143.

 Google Scholar

Chari A, Berdeja JG, Oriol A, et al. A phase 1, first-in-human study of talquetamab, a G protein-coupled receptor family C group 5 member D (GPRCIT005D) × CD3 bispecific antibody, in patients with relapsed and/or refractory multiple myeloma (RRMM). Blood. 2020;136(Suppl 1):40–41.

 Google Scholar

Berdeja JG, Krishnan AY, Oriol A, et al. Updated results of a phase 1, first-in-human study of talquetamab, a G protein-coupled receptor family C group 5 member D (GPRCIT005D) × CD3 bispecific antibody, in relapsed/refractory multiple myeloma (MM). J Clin Oncol. 2021;39(15_suppl): Abstract No.8008.

 Web of Science ®Google Scholar

Lonial S, Popat R, Hulin C, et al. Iberdomide (IBER) in combination with dexamethasone (DEX) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): results from the dose-expansion phase of the CC-220-MM-001 trial. Blood. 2021;138(suppl 1):162.

 Google Scholar

Richardson PG, Ramasamy K, Trudel S, et al. First-in-human phase I study of the novel CELMoD agent CC-92480 combined with dexamethasone (DEX) in patients (pts) with relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2020;38(15_suppl): Abstract No.8500.

 Google Scholar