Table 2.
Published clinical trials of CAR T-cell therapy in multiple myeloma.
| Target | Identifier (ref) | Phase | N | Pre-conditioning regimen | CAR- T dosage (cells/kg) | Prior treatments (mean) | Median follow-up (months) | Side effects | Clinical effects | Progression-free survival | BCMA− relapse |
|---|---|---|---|---|---|---|---|---|---|---|---|
| CD138 | NCT01886976 (26) | 1/2 | 5 | PCD/CP/VAD | 0.756 × 107 (median) | 10 | NR | 80% fever (G3) | SD (4) PD (1) | NR | NA |
| CD19 | NCT02135406 (27) | 1 | 10 | Mel + ASCT | 1–5 × 107 | 6 | NR | CRS (G1) (1) Intestinal GVHD (1) Mucositis (1) | sCR (1) VGPR (6) PR (2) | 200.8 days | NA |
| kappaLC | NCT00881920 (28) | 1 | 7 | Cy (4) or none (3) | 0.92 × −1.9 × 108 cells/m2 | 4 | NR | Lymphopenia (G3) (1) No CRS | SD (4) NR (3) | NA | NA |
| BCMA | NCT02215967 (29) | 1 | 24 | Cy + Flu | 0.3 × −9 × 106 | 9.5 | NR | 38% CRS (grade 3–4) 44% CRS (grade 1–2) Neurotoxicity (1) | 81% ORR sCR (2) VGPR (9) PR (4) | 31 weeks | 1 BCMA−progression |
| BCMA | NCT02546167 (30) | 1 | 25 | Cy or none | 1–5 × 107 or 1–5 × 108 | 7 | NR | 88% CRS (G ≥ 3: 8 patients) 32% neurotoxicity | ORR (48%) cohort 1 (44%), cohort 2 (20%), cohort 3 (64%) | 65, 57, 125 days (cohort 1, 2, or 3) | No BCMA- clones found |
| BCMA | NCT02658929 (31) | 1 | 33 | Cy + Flu | 50 × 150 × 450 × and 800 × 106 | 7-8 | 11.3 | 70% CRS (grade 1–2) 6% CRS (grade 3) 42% neurotoxicity | ORR (85%), ≥ CR (45%) sCR (36%) | 11.8 months | NR |
| BCMA | NCT03090659 (32) | 1 | 57 | Cy | 0.07–2.1 × 106 | 3 | 12 | 83% CRS (grade 1–2) 7% CRS (grade 3) Neurotoxicity (grade 1) (1) | 88% ORR (68% CR 5% VGPR 14% PR) | 15 mo (<40% BCMA+) 11 mo (>40% BCMA+) | NR |
| BCMA | NCT03430011 (33) | 1/2 | 44 | Cy + Flu | 50 × or 150 × 106 | 7 | 2.6 | 80% CRS (G≥3 9%) 25% neurotoxicity (G≥3 7%) | 82% ORR (27% CR) | NA | No relapses reported |
| BCMA | NA (34) | 1 | 11 | Cy or Flu + Cy | 72 × 137 × 475 × 818 × 106 | 6 | NR | 40% CRS (G1-2) 20% CRS (G3) 10% neurotoxicity (G2) | 64% ORR | NA | No relapses reported |
| BCMA | NCT03338972 (35) | 1 | 7 | Cy + Flu | 5 × or 15 × 107 | 8 | 3.7 | 86% CRS (G ≤ 2) No neurotoxicity | 100% ORR | NA | 1 BCMA− relapse |
| BCMA | NCT03288493 (36) | 1/2 | 23 | Cy + Flu | 0.75 × −15 × 106 | 6 | 137 days | 9,5% CRS (G1-2) 4.8% neurotoxicity (G2) | 63% ORR | NA | NR |
| BCMA | NCT03274219 (37, 38) | 1 | 22 | Cy + Flu | 150 × 450 × 800 × 1200 × 106 | 7 | 23 weeks | 59% CRS (5G1, 7G2, 1G3) 23% neurotoxicity (1G1, 2G2, 1G3, 1G4) | 83% ORR | NR | NA |
PCD, pomalidomide-cyclophosphamide-dexamethasone; CP, chlorambucil-prednisone; VAD, vincristine-doxorubicin-dexamethasone; PD, partial disease; Cy, cyclophosphamide; Flu, fludarabine; G, grade; Mel, melphalan; ASCT, autologous stem cell transplantation; NR, not reported; NA, non-applicable.