Safety and efficacy data of the 2 FDA- and EMA-approved CARs
| . | Idecabtagene vicleucel KarMMa trial1–3 . | Ciltacabtagene autoleucelCARTITUDE 1 trial . |
|---|---|---|
| Number of patients infused, n | 128 (140 apheresed) | 97 (120 apheresed) |
| Phase | 2 | 1b/2 |
| Target/costimulation | BCMA/4-1BB | BCMA/4-1BB *2 BCMA-targeting heavy-chain antibody |
| scFv | Chimeric mouse | Chimeric llama |
| Specificity | Autologous | Autologous |
| Follow-up, median (range) | 13.3 mo (0.2-21.2) | 21.7 mo (not reported) |
| Prior lines, median (range) | 6 (3 to 16) | 6 (3-18) |
| Triple-class refractory, n (%) | 108 (84) | 85 (87.6) |
| Penta-exposed, n (%) | 77 (60) | 81 (83.5) |
| Bridging therapy, n (%) | 112 (88) | 73 (75) |
| Response to bridging therapy, n (%) | 5/112 (4) | 33/73 (45) |
| EMD, n (%) | 50 (39) | 13 (13) |
| CAR T-cell dose | 150, 300, 450 × 106 CAR + T | 0.75 × 106 CAR T+/kg |
| LD chemotherapy | Fludarabine 30 mg/m2 × 3 d Cyclo 300 mg/m2 × 3 d | Fludarabine 30 mg/m2 × 3 d Cyclo 300 mg/m2 × 3 d |
| ORR, n (%) | 94 (73) At 450 × 106 (n = 54): 44 (81%) | 95 (97.9) |
| CR or sCR, n (%) | 42 (33) At 450 × 106 (n = 54): 21 (39) | 82.5% (sCR) |
| Time to first response, median (range) | 1.0 mo (0.5-8.8) | 1.0 mo (IQR 0.9-1.0) |
| MRD in CR, n (%) | 33/42 MRD neg (10−5) | 61 evaluable 92% MRD negative (10−5) |
| DOR, median (95% CI) | 10.7 mo (9.0-11.3) | Not reported |
| PFS, median (95% CI) | 8.8 mo (5.6-11.6) At 450 × 106 : 12.1 mo (8.8-12.3) | NR (16.8-NE) 2-y PFS: 60.5% (48.5-70.4) |
| PFS in high-risk, median (95% CI) | PFS at 2y, % (95% CI) | |
| ISS 3/R-ISS 3 | 4.9 mo (1.8-8.2)a | NE (NE-NE) |
| High-risk CA | 8.2 mo (4.8-11.9) | 48.4% (25.1-68.4) |
| Plasmacytomas | 7.9 mo (5.1-10.9) | 47.4% (24.4-67.3) |
| OS, median (95% CI) | 24.8 mo (19.9-31.2) | NR (27.2-NE) |
| CRS, n (%) | ||
| Overall | 107 (84) | 92 (95) |
| Grade 3-4 | 7 (5) | 4 (4) |
| Time to CRS onset, median (range) | 1 d (1-12) | 7 d (5-8) |
| Duration of CRS, median (range) | 5 d (1-63) | 4 d (3-6) |
| Neurotoxicity, n (%) | ||
| Overall | 23 (18) | 20 (21)b |
| Grade 3-4 | 4 (3) | 9 (9) |
| Time to neurotoxicity onset, median (range) | 2 d (1-10) | 8 d (6-8) for ICANs Other: CAR-T cell neurotoxicites: 26.5 d (11-108)b |
| Grade 3-4 neutropenia, n (%) | 114 (89) | 92 (95) |
| Time to recovery, median (range) | 1.9 mo (1.2-5.6) | Not reported |
| Grade 3-4 thrombocytopenia, n (%) | 67 (52) | 58 (60) |
| Time to recovery, median (range) | 2.1 mo (1.2-13.8) | Not reported |
| Infections, n (%) | 88 (69) | 56 (58) |
| Grade 3-4 infections, n (%) | 28 (22) | 19 (20) |
| Death, n (%) | 44 (34) | 14 |
| Reference | (1) Munshi et al9 (2) Anderson et al.34 (3) Oriol et al.35 | (4) Berdeja et al8 (5) Martin et al.36 (6) Jakubowiak et al11 |
| . | Idecabtagene vicleucel KarMMa trial1–3 . | Ciltacabtagene autoleucelCARTITUDE 1 trial . |
|---|---|---|
| Number of patients infused, n | 128 (140 apheresed) | 97 (120 apheresed) |
| Phase | 2 | 1b/2 |
| Target/costimulation | BCMA/4-1BB | BCMA/4-1BB *2 BCMA-targeting heavy-chain antibody |
| scFv | Chimeric mouse | Chimeric llama |
| Specificity | Autologous | Autologous |
| Follow-up, median (range) | 13.3 mo (0.2-21.2) | 21.7 mo (not reported) |
| Prior lines, median (range) | 6 (3 to 16) | 6 (3-18) |
| Triple-class refractory, n (%) | 108 (84) | 85 (87.6) |
| Penta-exposed, n (%) | 77 (60) | 81 (83.5) |
| Bridging therapy, n (%) | 112 (88) | 73 (75) |
| Response to bridging therapy, n (%) | 5/112 (4) | 33/73 (45) |
| EMD, n (%) | 50 (39) | 13 (13) |
| CAR T-cell dose | 150, 300, 450 × 106 CAR + T | 0.75 × 106 CAR T+/kg |
| LD chemotherapy | Fludarabine 30 mg/m2 × 3 d Cyclo 300 mg/m2 × 3 d | Fludarabine 30 mg/m2 × 3 d Cyclo 300 mg/m2 × 3 d |
| ORR, n (%) | 94 (73) At 450 × 106 (n = 54): 44 (81%) | 95 (97.9) |
| CR or sCR, n (%) | 42 (33) At 450 × 106 (n = 54): 21 (39) | 82.5% (sCR) |
| Time to first response, median (range) | 1.0 mo (0.5-8.8) | 1.0 mo (IQR 0.9-1.0) |
| MRD in CR, n (%) | 33/42 MRD neg (10−5) | 61 evaluable 92% MRD negative (10−5) |
| DOR, median (95% CI) | 10.7 mo (9.0-11.3) | Not reported |
| PFS, median (95% CI) | 8.8 mo (5.6-11.6) At 450 × 106 : 12.1 mo (8.8-12.3) | NR (16.8-NE) 2-y PFS: 60.5% (48.5-70.4) |
| PFS in high-risk, median (95% CI) | PFS at 2y, % (95% CI) | |
| ISS 3/R-ISS 3 | 4.9 mo (1.8-8.2)a | NE (NE-NE) |
| High-risk CA | 8.2 mo (4.8-11.9) | 48.4% (25.1-68.4) |
| Plasmacytomas | 7.9 mo (5.1-10.9) | 47.4% (24.4-67.3) |
| OS, median (95% CI) | 24.8 mo (19.9-31.2) | NR (27.2-NE) |
| CRS, n (%) | ||
| Overall | 107 (84) | 92 (95) |
| Grade 3-4 | 7 (5) | 4 (4) |
| Time to CRS onset, median (range) | 1 d (1-12) | 7 d (5-8) |
| Duration of CRS, median (range) | 5 d (1-63) | 4 d (3-6) |
| Neurotoxicity, n (%) | ||
| Overall | 23 (18) | 20 (21)b |
| Grade 3-4 | 4 (3) | 9 (9) |
| Time to neurotoxicity onset, median (range) | 2 d (1-10) | 8 d (6-8) for ICANs Other: CAR-T cell neurotoxicites: 26.5 d (11-108)b |
| Grade 3-4 neutropenia, n (%) | 114 (89) | 92 (95) |
| Time to recovery, median (range) | 1.9 mo (1.2-5.6) | Not reported |
| Grade 3-4 thrombocytopenia, n (%) | 67 (52) | 58 (60) |
| Time to recovery, median (range) | 2.1 mo (1.2-13.8) | Not reported |
| Infections, n (%) | 88 (69) | 56 (58) |
| Grade 3-4 infections, n (%) | 28 (22) | 19 (20) |
| Death, n (%) | 44 (34) | 14 |
| Reference | (1) Munshi et al9 (2) Anderson et al.34 (3) Oriol et al.35 | (4) Berdeja et al8 (5) Martin et al.36 (6) Jakubowiak et al11 |
Data from the KarMMa and CARTITUDE-1 pivotal trials with ide-cel and cilta-cel, respectively, are summarized.
PFS in R-ISS 3.
ICANS occurred in 16 (17%) patients. Other neurotoxicities occurred in 12 patients, with a median time to onset of 27 days. Five patients had a cluster of movement and neurocognitive treatment–emergent adverse events.
EMA: European Medicines Agency; EMD, extramedullary disease; FDA: US Food and Drug Administration.