Table 3 Summary of main trials evaluating anti-BCMA CAR-T cell therapy
Trials (N) | Construct | Baseline features | CAR-T cell dose | Lymphodepletion | RR | PFS (median) | CRS all/≥G3 (%) | ICANS all/≥G3 (%) |
|---|---|---|---|---|---|---|---|---|
Phase 1/2 | ||||||||
KarMMa/Ide-cel (N = 128) [97] | Lentivirus Murine scFv 4-1BB/CD3ζ | 6 y since diagnosis 6 prior lines HR cytogenetics: 35% Triple/Penta-refractory: 84/26% | 150-450 x 106 cells/kg | Cy/Flu | ORR 73%; ≥CR 33% MRD- at 10-5 79% a | 8.8 m | 84/5 | 18/3 |
EVOLVE/Orva-cel (N = 62) [98] | Lentivirus Human scFv 4-1BB/CD3ζ, EGFRt | 7 y since diagnosis 6 prior lines HR cytogenetics: 41% Triple/Penta-refractory: 94/48% | 300-600 x 106 cells | Cy/Flu | ORR 92%; ≥CR 36% MRD- at 10-5 84% | NR | 89/3 | 13/3 |
CARTITUDE-1/Cilta-cel (N = 97) [99] | Lentivirus Llama VHH1-24-1BB/CD3ζ | 5.9 y since diagnosis 6 prior lines HR cytogenetics: 23.7% Triple/Penta-refractory: 87.6/42.3% EMD: 13.4% | 0.5-1.0 x 106 cells/kg | Cy/Flu | ORR 96.9%; ≥CR 67% MRD- at 10-5 54.6% | At 12-m, 76.6 | 94.8/5 | 16.5/2.1 |
PRIME/P-BCMA-101 (N = 53) [100] | PiggyBac Human Centyrin 4-1BB/CD3ζ | 4.9 y since diagnosis 8 prior lines Triple-refractory: 60% | 51-1178 x 106 cells Q2W cycles or combined with Rix or Lena | Cy/Flu | ORR 56.7% (out of 30 evaluable pts) | NR | 17/0 | 3.8/3.8 |
LUMMICAR-2/CT053 (N = 20) [101] | Lentivirus Human scFv 4-1BB/CD3ζ | 6 y since diagnosis 5 prior lines HR cytogenetics: 55% Triple/Penta-refractory: 85/50% EMD: 25% | 1.5-3 x 108 cells | Cy/Flu | ORR 94%; ≥CR 27.8% (out of 18 pts with ≥8 w of follow-up) | NR | 78.9/0 | 15.8/5.3 |
Phase 1 | ||||||||
NCI [102] (N = 16) [102] | γ-retrovirus Murine scFv CD28/CD3ζ | 9.5 prior lines HR cytogenetics: 40% | 9 x 106 cells/kg | Cy/Flu | ORR 81%; ≥CR 12.5% MRD- at 10-5 75% | EFS, 31 w | 94/37.5 | NR/19 |
CAR-T BCMA/UPenn (N = 25) [103] | Lentivirus Human scFv 4-1BB/CD3ζ | 4.6 y since diagnosis 7 prior lines HR cytogenetics: 96% Penta-refractory: 44% | C1: 1-5 x 108 cells C2: 1-5 x 107 cells C3: 1-5 x 108 cells | C1: No C2: Cy C3: Cy | C1: ORR 44%; ≥CR 9% C2: ORR 20%; ≥CR 0% C3: ORR 64%; ≥CR11% | C1: 65 d C2: 57 d C3: 125 d | C1: 89/33 C2: 60/0 C3: 100/45 | C1: 33/22 C2: 20/0 C3: 36/9 |
CRB-402/bb21217 (N = 69) [104] | Lentivirus Murine scFv 4-1BB/CD3ζ bb007 PI3K inh | 5.7 y since diagnosis 6 prior lines HR cytogenetics: 33% Triple-refractory: 64% | C1: 150 x 106 cells C2: 300 x 106 cells C3: 450 x 106 cells Exp: 450 x 106 cells | Cy/Flu | C1: ORR 83%; ≥CR 42% C2: ORR 43%; ≥CR 14% C3: ORR 57%; ≥CR 29% Exp: ORR 84%; ≥CR 32% | NR | 70/4 | 16/4 |
MSKCC/MCARH171 (N = 11) [98] | γ-retrovirus Human scFv 4-1BB/CD3ζ, EGFRt | 6 prior lines HR cytogenetics: 82% | 72-818 x 106 cells | Cy or Cy/Flu | ORR 64% (≥CR 0%) | NR | 60/20 | 10/0 |
FHCRC/FCARH143 (N = 7) [105] | Lentivirus Human scFv 4-1BB/CD3ζ, EGFRt | 8 prior lines HR cytogenetics: 100% | 50-800 x 106 cells | Cy/Flu | ORR 100% (≥CR 36%) | NR | 91/0 | 9/0 |
HRAIN Biotechnology (N = 20) [106] | γ-retrovirus Murine scFv 4-1BB/CD3ζ, EGFRt | 5.5 prior lines | 9 x 106 cells/kg | Cy/Flu | ORR 79% (≥CR 45%) | 15 m | 45/5 | NR/7 |
FHVH-BCMA (N = 12) [107] | γ-retrovirus FHVH33 4-1BB/CD3ζ, EGFRt | 6 prior lines HR cytogenetics: 58% | 0.75-3 x 106 cells/kg | Cy/Flu | ORR 83% (≥CR 17%) | NR | 91.7/8.3 | 25/8.3 |
CT103A (N = 14) [108] | Lentivirus Human scFv 4-1BB/CD3ζ | 4 prior lines | 1-6 x 106 cells/kg | Cy/Flu | ORR 100% (≥CR 71%) | NR | 94.4/28 | 0/0 |
C-CAR088 (N = 23) [109] | Lentivirus Human scFv 4-1BB/CD3ζ | 4 prior lines | 1-6 x 106 cells/kg | Cy/Flu | ORR 95.7% (≥CR 43.5%) | At 6-m: 65.1% | 91.3/4.3 | 4.3/0 |
UNIVERSAL/ ALLO-715 (N = 31) [110] | Lentivirus Human scFv Rix-RD 4-1BB/CD3ζ Allogeneic TC with disrupted TCRα and CD52 | 5.4 y since diagnosis 5 prior lines HR cytogenetics: 48% | 40-480 x 106 cells | ALLO-647/ Cy +/- Flu | ORR 62% (≥VGPR 38%) at 320 x106 cells (n=13) | NR | 45/0 | 0/0 |