Table 1.
Selected landmark clinical trials of BCMA-targeted CAR T cells in RRMM (with n > 10)
| Study | n | Phase | Vector | Product | Costimulatory domain | LD chemotherapy | CAR T-cell dose | Lines of prior treatment, median (range), n | Triple class refractory, % | Previous ASCT, % | CRS any grade, % | CRS grade ≥3, % | ICANS grade ≥3, % | Anti–IL-6 therapy, % | ORR, % | ≥VGPR, % | CR, % | MRD negative, %* | PFS, median | OS, median |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CRB-4013 | 33 | 1 | Lenti | Ide-cel (bb2121) | 4-1BB | Flu/Cyc | 50/150/450/800 × 106 cells | 7 (3-23) | N/A | 97 | 76 | 6 | 3 | 21 | 85 | 72 | 45 | 94 (15/16; ≥PR patients) | 11.8 mo | N/A |
| KarMMA4 | 128 | 2 | Lenti | Ide-cel (bb2121) | 4-1BB | Flu/Cyc | 150/300/450 × 106 cells | 6 (3-16) | 84 | 94 | 84 | 6 | 3 | 2 | 73 | 53 | 33 | 33 (26/128; CR patients) | 8.8 mo | 19.4 mo |
| LEGEND-29 | 57/74 | 1 | Lenti | LCAR-B38M (JNJ68284528) | 4-1BB | Cyc | 0.5 × 106 (0.07-2.1) cells/kg | 3 (1-9) | N/A | 18 | 90 | 7 | 0 | 46 | 89 | 78 | 74 | 68.4 (39/57; CR patients) | 19.9 mo | 36.1 mo |
| CARTITUDE-17,50 | 29 | 1b/2 | Lenti | LCAR-B38M (JNJ68284528) | 4-1BB | Flu/Cyc | 0.75 × 106 (0.5-1.0) cells/kg | 5 (3-18) | 86 | 86 | 93 | 7 | 3 | 76 | 100 | 97 | 86 | 81 (13/16; CR patients) | 87% (9 mo) | N/A |
| EVOLVE5 | 44 | 1 | Lenti | Orvacabtagene autoleucel (JCARH125) | 4-1BB | Flu/Cyc | 50/150/450 × 106 cells | 7 (3-23) | N/A | 68 | 80 | 9 | 7 | 34 | 82 | 48 | 27 | 67 (6/9) at day 29 (≥PR patients) | N/A | N/A |
| EVOLVE47 | 62 | 1 | Lenti | Orvacabtagene autoleucel (JCARH125) | 4-1BB | Flu/Cyc | 300/450/600 × 106 cells | 6 (3-18) | 94 | 94 | 89 | 3 | 3 | 76 | 92 | 68 | 35 | 96 (21/25) at 3 mo (≥PR patients) | N/A | N/A |
| NCI13 | 16 | 1 | Retro | N/A | CD28 | Flu/Cyc | 9 × 106 cells/kg | 9.5 (3-19) | N/A | N/A | 94 | 38 | 19 | 31 | 81 | 63 | 13 | 100 (≥PR patients) | 31 wk | N/A |
| UPENN14 | 25 | 1 | Lenti | N/A | 4-1BB | None or Cyc | 10/50/100/500 × 106 cells | 7 (3-13) | 44 | 92 | 88 | 32 | 12 | 28 | 63 | 28 | 8 | 33 (≥PR patients) | 65-125 d | 502 d |
| P-BCMA-10145 | 23 | 1/2 | PiggyBac transposon | P-BCMA-101 | 4-1BB | Flu/Cy | 51/152/456/845/1143 × 106 cells | 6 (3-11) | N/A | 83 | 10 (2/21) | 0 | 5 (1/21) | 5 (1/21) | 63 (12/19) | 26 (5/19) | N/A | N/A | N/A | N/A |
| FHCRC6 | 11 | 1 | Lenti | FCARH143 | 4-1BB | Yes (not specified) | 50/150 × 106 cells | 11 (8-20) | 91 | 82 | 18 | 0 | 0 | 18 | 100 | 82 | 36 | N/A | N/A | N/A |
| CT05351 | 24 | 1 | Retro | CT053 | 4-1BB | Flu/Cyc | 150 × 106 cells | 4.5 (2-11) | N/A | 42 | 63 | 0 | 4 | 53 (8/15) | 88 | 83 | 79 | 85 (17/20) | N/A | N/A |
| CT103A52 | 18 | 1 | Lenti | CT103A | 4-1BB | Flu/Cyc | 1/3/6/8 × 106 cells/kg | 4 (3-6) | N/A | 39 | 94 | 22 | 0 | N/A | 100 (17/17) | 88 (15/17) | 71 (12/17) | 100 at 10−4 (≥PR patients) | N/A | N/A |
ASCT, autologous stem cell transplant; Cyc, cyclophosphamide; Flu, fludarabine; ICANS, immune effector cell associated neurotoxicity syndrome; IL-6, interleukin-6; Lenti, lentivirus; N/A, not available or not applicable; OS, overall survival; PFS, progression-free survival; Retro, retrovirus.
*
MRD negative at a sensitivity of 10−5 cells.