Approved and selected investigational BCMA-targeted therapies for use in late-line MM*
| Agent (reference) . | Construct . | Trial (NCT#, status) . | Phase . | Design . | n . | % ORR (% ≥CR); median DOR in months (95% CI); median PFS in months (95% CI) at reported median follow-up . | Selected safety event % (G3 + 4%, if any) . |
|---|---|---|---|---|---|---|---|
| Belantamab mafodotin (belamaf)3† | Antibody-drug conjugate | DREAMM-2 (NCT03525678, active, not recruiting) | 2 | Open-label, 2-arm, randomized to receive 2.5 mg/kg or 3.4 mg/kg RP2D | 196 | 2.5 mg/kg: 31% (3% ≥ CR), 13.7 (9.9-NE); 2.9 (2.1-3.7) at 13 months 3.4 mg/kg: 34% (3% ≥ CR); NR; 4.9 (2.3-6.2) | 2.5 mg/kg: keratopathy 70% (27%), thrombocytopenia 35% (20%), anemia 24% (20%) 3.4 mg/kg: keratopathy 75% (21%), thrombocytopenia 54% (30%), anemia 37% (25%) |
| Idecabtagene vicleucel (ide-cel)5 | Autologous CART | KarMMa-1 (NCT03361748, active, not recruiting) | 1/2 | Open-label, single-arm, dose escalation and dose expansion | 128 | ORR 73% (33% ≥ CR); 10.7 (9.0-11.3); 8.8 (5.6-11.6) | CRS 84% (5%), neurotoxicity 18% (3%), neutropenia 91% (89%), anemia 91% (60%), thrombocytopenia 63% (52%), hypogammaglobulinemia (21%) |
| Ciltacabtagene autoleucel (cilta-cel)7 | Autologous CART | CARTITUDE-1 (NCT03548207, completed) | 1/2 | Open-label, single-arm, dose escalation and dose expansion | 97 | 97% (sCR 82.5%); 33.9 (25.5-NE); 34.9 (25.2-NE) | CRS 95% (4%), neurotoxicity 21% (9%), neutropenia 91% (89%), anemia 93% (95%), thrombocytopenia 81% (68%) |
| Teclistamab6‡ | BsAb (humanized IgG4) | MajesTec-1 (NCT04557098, recruiting) | 1/2 | Open-label, nonrandomized, IV or SC teclistamab in RRMM, dose expansion and dose escalation | 165 | 63% (43% ≥ CR); 24 (24-NE); 12.5 (8.8-17.2) at 22 months | CRS 72.1% (0.6%), neurotoxicity 14.5% (0.6%), neutropenia 70.9% (64.2%), anemia 52.1% (37%), pneumonia 18.2% (12.7%), COVID-19 17.6% (12.7%), hypogammaglobulinemia 74.5% (0%) |
| Elranatamab38‡ | BsAb (humanized IgG2a) | Magnetissm-3 (NCT04649359, active, not recruiting) | 2 | Open-label, multicenter, nonrandomized, single-agent SC | 123 | 61% (28% ≥ CR); NE (12-NE); NE (10.4-NE) at 10.4 months | CRS 57.7% (0%), neurotoxicity 3.4% (0%), peripheral neuropathy 17.1% (0.8%), infections 66.7% (35%) |
| Linvoseltamab (REGN5458)39‡ | BsAb (Veloci-Bi antibody) | LINKER-MM1 (NCT03761108, active, not recruiting) | 1/2 | Open-label, multicenter, nonrandomized, single-agent IV | 87 | 64% (24% ≥ CR); NE; NE at 3.2 months | CRS 37% (1%), ICANS 5.6% (1.2%), anemia 28% (24%), neutropenia 20% (17%), thrombocytopenia 15% (10%), infections 54% (29%) |
| Alnuctamab (CC-93269)40‡ | BsAb (2 + 1 humanized IgG1) | (NCT03486067, recruiting) | 1 | Open-label, multicenter, nonrandomized, single-agent IV or SC | 70 (IV), 68 (SC) | IV: 39%; 33.6 (10.6-NE); 3.1 (1.9-5.5) at 8 months SC: 53% (16%,7%); NE; NR at 4.1 months | CRS 53% (0%), peripheral neuropathy 6% (0%), ICANS 3% (0%), anemia 38% (25%), neutropenia 37% (32%), infections 34% (9%) |
| ABBV-383B41‡ | BsAb (2 + 1 humanized IgG4) | (NCT05286229, active, not recruiting) | 1b | Open-label, multicenter, nonrandomized, single-agent IV | 55 (40 mg), 61 (60 mg) | 40 mg: 58% (13% ≥ CR); NE (4.3); 13.7 (3.1-NE) at 3.5 months 60 mg: 61% (34% ≥ CR); NE (10.4); 11.2 (4.8-NE) at 12.7 months | CRS 60% (1%), ICANS 4.9% (1.6%), anemia 37% (16%), neutropenia 34% (26%), thrombocytopenia 29% (11%), infections NR (22%) |
| Agent (reference) . | Construct . | Trial (NCT#, status) . | Phase . | Design . | n . | % ORR (% ≥CR); median DOR in months (95% CI); median PFS in months (95% CI) at reported median follow-up . | Selected safety event % (G3 + 4%, if any) . |
|---|---|---|---|---|---|---|---|
| Belantamab mafodotin (belamaf)3† | Antibody-drug conjugate | DREAMM-2 (NCT03525678, active, not recruiting) | 2 | Open-label, 2-arm, randomized to receive 2.5 mg/kg or 3.4 mg/kg RP2D | 196 | 2.5 mg/kg: 31% (3% ≥ CR), 13.7 (9.9-NE); 2.9 (2.1-3.7) at 13 months 3.4 mg/kg: 34% (3% ≥ CR); NR; 4.9 (2.3-6.2) | 2.5 mg/kg: keratopathy 70% (27%), thrombocytopenia 35% (20%), anemia 24% (20%) 3.4 mg/kg: keratopathy 75% (21%), thrombocytopenia 54% (30%), anemia 37% (25%) |
| Idecabtagene vicleucel (ide-cel)5 | Autologous CART | KarMMa-1 (NCT03361748, active, not recruiting) | 1/2 | Open-label, single-arm, dose escalation and dose expansion | 128 | ORR 73% (33% ≥ CR); 10.7 (9.0-11.3); 8.8 (5.6-11.6) | CRS 84% (5%), neurotoxicity 18% (3%), neutropenia 91% (89%), anemia 91% (60%), thrombocytopenia 63% (52%), hypogammaglobulinemia (21%) |
| Ciltacabtagene autoleucel (cilta-cel)7 | Autologous CART | CARTITUDE-1 (NCT03548207, completed) | 1/2 | Open-label, single-arm, dose escalation and dose expansion | 97 | 97% (sCR 82.5%); 33.9 (25.5-NE); 34.9 (25.2-NE) | CRS 95% (4%), neurotoxicity 21% (9%), neutropenia 91% (89%), anemia 93% (95%), thrombocytopenia 81% (68%) |
| Teclistamab6‡ | BsAb (humanized IgG4) | MajesTec-1 (NCT04557098, recruiting) | 1/2 | Open-label, nonrandomized, IV or SC teclistamab in RRMM, dose expansion and dose escalation | 165 | 63% (43% ≥ CR); 24 (24-NE); 12.5 (8.8-17.2) at 22 months | CRS 72.1% (0.6%), neurotoxicity 14.5% (0.6%), neutropenia 70.9% (64.2%), anemia 52.1% (37%), pneumonia 18.2% (12.7%), COVID-19 17.6% (12.7%), hypogammaglobulinemia 74.5% (0%) |
| Elranatamab38‡ | BsAb (humanized IgG2a) | Magnetissm-3 (NCT04649359, active, not recruiting) | 2 | Open-label, multicenter, nonrandomized, single-agent SC | 123 | 61% (28% ≥ CR); NE (12-NE); NE (10.4-NE) at 10.4 months | CRS 57.7% (0%), neurotoxicity 3.4% (0%), peripheral neuropathy 17.1% (0.8%), infections 66.7% (35%) |
| Linvoseltamab (REGN5458)39‡ | BsAb (Veloci-Bi antibody) | LINKER-MM1 (NCT03761108, active, not recruiting) | 1/2 | Open-label, multicenter, nonrandomized, single-agent IV | 87 | 64% (24% ≥ CR); NE; NE at 3.2 months | CRS 37% (1%), ICANS 5.6% (1.2%), anemia 28% (24%), neutropenia 20% (17%), thrombocytopenia 15% (10%), infections 54% (29%) |
| Alnuctamab (CC-93269)40‡ | BsAb (2 + 1 humanized IgG1) | (NCT03486067, recruiting) | 1 | Open-label, multicenter, nonrandomized, single-agent IV or SC | 70 (IV), 68 (SC) | IV: 39%; 33.6 (10.6-NE); 3.1 (1.9-5.5) at 8 months SC: 53% (16%,7%); NE; NR at 4.1 months | CRS 53% (0%), peripheral neuropathy 6% (0%), ICANS 3% (0%), anemia 38% (25%), neutropenia 37% (32%), infections 34% (9%) |
| ABBV-383B41‡ | BsAb (2 + 1 humanized IgG4) | (NCT05286229, active, not recruiting) | 1b | Open-label, multicenter, nonrandomized, single-agent IV | 55 (40 mg), 61 (60 mg) | 40 mg: 58% (13% ≥ CR); NE (4.3); 13.7 (3.1-NE) at 3.5 months 60 mg: 61% (34% ≥ CR); NE (10.4); 11.2 (4.8-NE) at 12.7 months | CRS 60% (1%), ICANS 4.9% (1.6%), anemia 37% (16%), neutropenia 34% (26%), thrombocytopenia 29% (11%), infections NR (22%) |
sCR, stringent complete response; NE, not estimable/reached; NR, not reported; RRMM, relapsed and refractory multiple myeloma.
Nonexhaustive list of selected trials (search May 18, 2023)—for a comprehensive list, please visit clinicaltrials.gov.
Withdrawn from the US market in late 2022 due to a negative phase 3 trial (DREAMM-3).
Updated data as presented during ASH 2022 or ASCO 2023 meetings.