Table 2.
Published results of multiple myeloma CAR-T cell clinical trials targeting antigens other than BCMA.
| n = (ref.) | Antigen | Signaling domains | Cell source/type | Transfer method | Conditioning | T-cell dosage | Therapy-related side effects | Clinical effects |
|---|---|---|---|---|---|---|---|---|
| n = 1 (31) | CD138 | ND | Autologous T cells | ND | CP/Flu | 1.5 × 108 | • CRS gr. 2 (1) | • PR (1) |
| n = 5 (32) | CD138 | 4-1BB/CD3ζ | Autologous T cells | Lentiviral | PCD, CP or VAD | 0.756 × 107/kg | • Infusion-related fever (4) | • SD > 3 m (4) |
| • Nausea and vomiting (3) | • ↓ circulating PCL cells (1) | |||||||
| • ↑ Liver function tests (1) | ||||||||
| • Possible TLS (1) | ||||||||
| n = 10 (33) | CD19 | 4-1BB/CD3ζ | Autologous T cells | Lentiviral | HDM + ASCT | 1–5 × 107 | • Hypogammaglobulinemia (1) | • CR (1) |
| • Autologous GvHD (1) | • VGPR (6/10) at d100 post-ASCT | |||||||
| • Mucositis (1) | • PR (2/10) at d100 post-ASCT | |||||||
| n = 5/8 (34) | CD19 + BCMA | OX40/CD28 | Autologous or allogeneic T cells | Lentiviral | CP/Flu | 1 × 107/kg | • CRS gr. 1–2 (7), gr.≥3 (1) | • sCR (1/5) |
| • Prolonged cytopenias (5/5) | • VGPR (1/5) | |||||||
| • Coagulopathy (5) | • PR (2/5) | |||||||
| • ↑ Liver function tests (4) | • SD (1/5) | |||||||
| • Pulmonary edema (3) | ||||||||
| • Pleural effusion and ascites (1) | ||||||||
| n = 10 (35) | CD19 + BCMA | OX40/CD28 | Autologous T cells | Lentiviral | Bu-CP + ASCT | 1 × 107/kg | • CRS gr. 1–2 (10) | • CR (7/10) |
| • Coagulopathy (7) | • VGPR (3/10) | |||||||
| • ↑ Troponin levels (4) | ||||||||
| • Atrial flutter (1) | ||||||||
| n = 5 (36) | NKG2D ligands | CD3ζ | Autologous T cells | Retroviral | None | 1–3 × 106−7 | • None | • None |
| n = 7 (37) | κLC | CD28/CD3ζ | Autologous T cells | Retroviral | CP (4) | 0.92–1.9 × 108/m2 | • Lymphopenia gr. 3 (1) | • SD 6 wk−24m (4) |
| or none (3) |
Only fully published clinical studies were included (last search: May 1, 2019). n =, number of patients; (ref.), bibliography reference; ASCT, autologous stem cell transplantation; BCMA, B cell maturation antigen; Bu, busulphan; CP, cyclophosphamide; CRS, cytokine release syndrome; d, days; Flu, fludarabine; GvHD, graft-vs.-host disease; HDM, high-dose melphalan; κLC, kappa light chain; m, months; ND, no data; NKG2D, natural killer group 2, member D; PCD, pomalidomide-cyclophosphamide-dexamethasone; PCL, plasma cell leukemia; PR, partial response; (s)CR, (stringent) complete response; SD, stable disease; TLS, tumor lysis syndrome; VAD, vincristine-doxorubicin-dexamethasone; VGPR, very good partial response; wk, weeks.