CAR-T and Bispecific Antibodies: The New Standard for Relapsed and Refractory Multiple Myeloma, or Reserved for Late-Line Salvage Therapy?
Abstract
:1. Introduction
2. Point: CAR-T and Bispecific Antibodies Are Not Yet the Standard for RRMM
3. Counterpoint: CAR-T and Bispecific Antibodies Will Rapidly Become the Standard for the Treatment of RRMM
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Phase | Target | Binder and Costim | Age (Range) | Disease Setting | # of Lines | HR Cyto, % | EMD, % | Triple-R, % | CRS: Any Grade, 3/4 | Neuro: Any Grade, 3/4 | ORR, % | CR/sCR, % | PFS | Ref. | |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Ide-cel KarMMa (n = 128) | II | BCMA | scFv Murine 4-1BB | 61 (33–78) | RRMM | 6 | 35 | 39 | 84 | 84/5 | 18/3 | 81 ^ | 39 ^ | 12.1 ^ m | [1] |
Ide-cel KarMMa-3 (n = 386) | III | 63 (30–81) | 2–4 PLT | 3 | 42 | 24 | 65 | 88/4 | 15/3 | 71 | 39 | 13.3 m | [4] | ||
Cilta-cel CARTITUDE-1 (n = 97) | Ib/II | BCMA | VHH, Camelid 4-1BB | 61 (56–68) | RRMM | 6 | 24 | 13 | 88 | 95/4 | 21/9 | 98 | 82 | 34.9 m | [5,6] |
Cilta-cel CARTITUDE4 (n = 419) | III | 61.5 (27–78) | 1–3 PLT | 2 | 35 | 21 | 14 | 74.5/1.1 | 20.5/2.8 | 85 | 73 | 76%@12 m | [7] | ||
ARI0002h (n = 60) | I/II | BCMA | scFv Human | 58 (36–74) | RRMM | 3 | 28 | 18 | NR | 90/5 | 3/0 | 95 | 58 | 15.8 m | [8] |
ddBCMA (n = 40) | I | BCMA | Synthetic 4-1BB | 66 (44–76) | RRMM | 4 | 29 | 34 | 100 | 95/3 | 18/5 | 100 | 76 | 74%@12 m | [9] |
GC012F FasTCAR (n = 22) | I | BCMA/ CD19 | scFv | 59 (43–69) | NDMM | 1 | 32 * | 55 | 0 | 27/0 | 0/0 | 100 | 95.5 | NR | [10] |
CC-95266 (n = 84) | I | GPRC5D | scFv, Human | 63 (39–80) | RRMM | 5 | 44 | 41 | 74 | 76/4 | ICANS 10/2 (non-ICANS 11/4) | 88 | 45 | NR | [11] |
Bispecific Antibody | Teclistamab (JNJ6400795) [18] | Elranatamab (PF-06863135) [19] | Linvoseltamab (REGN5458) [20,21] | Talquetamab (JNJ-64407564) [22,23] | Cevostamab (GO39775) [24,25] | |
---|---|---|---|---|---|---|
Structure/Function | BCMA-CD3 | BCMA-CD3 | BCMA-CD3 | GPRC5D-CD3 | FcRH5 X CD3 | |
Treatment | Weekly SC | Weekly SC | Weekly IV | Weekly SC | Bi-weekly SC | Every 3 weeks IV, up to 17 cycles |
Patients (n; age) | n = 165; 64 (33–84) | n = 123; 68 (36–89) | n = 117; 70 (37–91) | n = 143; 67 (46–86) | n = 145; 67 (38–84) | n = 161; 64 (33–82) |
Median prior lines | 5 | 5 | 5 | 5 | 5 | 6 |
HR cyto/EMD TCR | 26%/17% 78% | 25%/32% 97% | 36%/14% 74% | 31%/23% 74% | 29%/26% 69% | 40%/21% 85% |
ORR/CR (at RP2D) RP2D | 63%/39.2% 1.5 mg/kg | 61%/35% 76 mg | 71%/46% 200 mg | 74%/34% 0.4 mg/kg | 72%/32% 0.8 mg/kg | 57%/8.4% 132–198 mg |
PFS | 11.3 mos | 51@15 mos | 69%@12 mos | 7.5 mos | 11.9 mos | NR |
DOR | 18.4 mos | 71.5@15 mos | 78%@12mos | 9.3 mos | 13 mos | 11.5 mos |
Median f/u | 14.1 mos | 14.7 mos | 11 mos | 18.8 mos | 12.7 mos | 8.8 mos |
CRS (all/Gr3+) | 72.1% (0.6%) | 58% (0%) | 46% (1%) | 79% (02.1%) | 72.4% (0.7%) | 81% (1.2%) → toci prophy: 36% (2.3%) |
Infections (all/Gr3+) | 76.4% (45%) | 70% (40%) | 73% (34%) | 57% (17%) | 51% (12%) | ~48% (20%) |
Neutropenia (all/Gr3+) | 71% (64%) | 49% (49%) | 42% (40%) | 34% (31%) | 28% (22%) | ~39% (37%) |
Anemia Thrombocytopenia (all/Gr3+) | 52% (37%) 40% (21%) | 49% (37%) 31% (24%) | 36% (31%) 18% (6%) | 45% (31% 27% (20%) | 39% (25%) 27% (17%) | ~36% (16%) ~28% (18%) |
Neurotoxicity ICANS (all/Gr+) Other | 3% (0%) 10% (0%) | 3.4%/0% PN 17.1 | 8% (3%) | 10.7% (1.6%) | 10.1% (1.8%) | ~14% (1%) |
Hypogamma (IVIg replacement) | 75% (39)% | NR | NR | 64% (15%) | 68% (13%) | NR |
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Rodriguez-Otero, P.; Martin, T. CAR-T and Bispecific Antibodies: The New Standard for Relapsed and Refractory Multiple Myeloma, or Reserved for Late-Line Salvage Therapy? Hemato 2024, 5, 171-179. https://doi.org/10.3390/hemato5020014
Rodriguez-Otero P, Martin T. CAR-T and Bispecific Antibodies: The New Standard for Relapsed and Refractory Multiple Myeloma, or Reserved for Late-Line Salvage Therapy? Hemato. 2024; 5(2):171-179. https://doi.org/10.3390/hemato5020014
Chicago/Turabian StyleRodriguez-Otero, Paula, and Thomas Martin. 2024. "CAR-T and Bispecific Antibodies: The New Standard for Relapsed and Refractory Multiple Myeloma, or Reserved for Late-Line Salvage Therapy?" Hemato 5, no. 2: 171-179. https://doi.org/10.3390/hemato5020014