Table 2.
Selection of ongoing and completed clinical trials with CAR-T cells for the treatment of multiple myeloma
| antigen | trial site | scFv | signaling domains |
safety gene |
gene transfer |
conditioning therapy |
T-cell dose | patients treated |
reported responses |
clinical trial identifier, ref. |
|---|---|---|---|---|---|---|---|---|---|---|
| CD138 | PLA General Hospital Beijing | NK-92 | 4-1BB/CD3ζ | - | lentiviral | various | 0.44×106-3.78×106 CAR+ T cells/kg | 5 | SD (4 pts) | NCT01886976 [44] |
| κ light chain | Baylor College of Medicine | CRL-1758 | CD28/ CD3ζ | - | gamma-retroviral | Cy 12.5 mg/kg | 2×107; 1×108; 2×108 CAR+ T cells/m2 | 7 | SD (4 pts) | NCT00881920 [49] |
| CD19 | University of Pennsylvania | FMC63 | 4-1BB/CD3ζ | - | lentiviral | Mel 140–200 mg/m2 +HSCT, AT d12-14 | 1–5×107 CAR+ T cells | 10 | longer PFS than after 1st ASCT in 2 pts | NCT02135406 [50,79] |
| BCMA | National Cancer Institute | 11D5-3 | CD28/ CD3ζ | - | gamma-retroviral | Cy 300 mg/m2 ×3 + Flu 30 mg/m2 ×3 | 0.3–9.0×106 CAR+ T cells/kg | 26 | sCR (2 pts), VGPR (9), PR (4), SD (10), PD (1) | NCT02215967 [55] |
| BCMA | Bluebird Bio, multicenter | NR, murine | 4-1BB/CD3ζ | - | lentiviral | Cy 300 mg/m2 ×3 + Flu 30 mg/m2 ×3 | 5, 15, 45 and 80×107 CAR+ T cells | 33 | 21 pts evaluable (escalation phase): CR (10 pts), VGPR (6), PR (2), SD (1), PD (2) | NCT02658929 [56] |
| BCMA | University of Pennsylvania | NR, human | 4-1BB/CD3ζ | - | lentiviral | none or Cy 1500 mg/m2 | 1–5×107 or 1–5×108 CAR+ T cells | 24 | CR (2 pts), VGPR (3), PR (6), MR (5), SD (5), PD (3) | NCT02546167 [57] |
| BCMA | Nanjing Legend Biotech | NR | NR | - | lentiviral | Cy 300 mg/m2 ×3 | 1.5–7.0×106 CAR+ T cells/kg | 35 | CR (15 pts), VGPR (13), PR (7) | NCT03090659 [59] |
| BCMA | Memorial Sloan Kettering Cancer Center | NR, human | 4-1BB/CD3ζ | EGFRt | gamma-retroviral | Cy 3000 mg/m2 or Cy 300 mg/m2 ×3 + Flu 30 mg/m2 ×3 | 1×106 CAR+ T cells/kg; 15, 45 and 80×107 CAR+ T cells | 6 | 4 pts evaluable: VGPR (2), PR (1), SD (1) | NCT03070327 [58] |
| BCMA/ CD19 | First Affiliated Hospital, Soochow Univ. | NR | CD28/OX40 /CD3ζ | - | lentiviral | Cy 300 mg/m2 ×3 + Flu 30 mg/m2 ×3 | 5–50×106 CAR+ T cells/kg | 10 | CR (2), VGPR (1), PR (6), MR (1) | NCT03196414 [81] |
Abbreviations: SD - stable disease; Cy - cyclophosphamide; Mel - melphalan; HSCT - hematopoietic stem cell transplantation; AT - adoptive transfer; PFS - progression free survival; Flu - fludarabine; VGPR - very good partial response; PR - partial response; NR - not reported; F/U -follow-up; MR - minor response, EGFRt – truncated epidermal growth factor receptor.