Table 3. . Chimeric antigen receptor T cells in multiple myeloma.
| Author (year) study design | Number of patients | Median number of prior therapy lines | Lympho-depletion therapy | CAR T-cell type | Intracellular domain | CARTs dose | Targeted antigen, location | Outcome | Cytokine-release syndrome | Other adverse effects | Ref. |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Ali et al. (2016) Phase I | 12 | 7 | CF | CAR-BCMA | CD28 ICD-CD3zeta | 0.3–9 × 106/kg | BCMA, normal plasma cells, malignant plasma cells, some B cells | 0.3 × 106 = 1 PR (2 wk), 2 SD (6 wk) 1 × 106 = 3 SD (2–12 wk) 3 × 106 = 1 VGPR (8 wk), 3 SD (2–8 wk) 9 × 106 = 1 sCR (17 wk), 1 VGPR (26+ wk) |
1 × 106 = mild (2 pt) 3 × 106 = mild (3 pt) Severe (1 pt) 9 × 106 = severe (2 pt) (required tocilizumab) |
Anemia, neutropenia, nausea, hypocalcemia, hypophosphatemia | [64] |
| Fan et al. (2017) Phase I | 35 (19 REP) |
Not specified | Not reported | LCAR-B38M | NS | 0.6–7 × 106/kg | As above | ORR: 100% 14 sCR (8 wk) 1 PR (8 wk) 4 VGPR (8 wk) |
Overall 74% 9 Grade I 2 Grade II 1 Grade III 1 Grade IV |
Anemia fever dyspnea | [65] |
| Cohen et al. (2016) Phase I | 6 | 9 | Not reported | CAR-BCMA | 4-1BB ICD-CD3zeta | 1–5 × 108/pt | As above | 1.8 × 108 = 1 PD 2 × 108 = 1 VGPR (5 m) 1 sCR (7+ m) 5 × 108 = 1 MR (1+ m) 1 MR (2 m) 1 SD (2 m) |
83% 2 Grade I 1 Grade II 2 Grade III (required tocilizumab) |
Anemia, neutropenia, pleural effusion (16%), hypocalcemia (33%) hypophosphatemia (50%) PRES: 1 Grade IV |
[66] |
| Berdeja et al. (2016) Phase I | 9 | 6 | CF | bb2121 anti-BCMA CAR T cells | 4-1BB ICD-CD3zeta | 5–45 × 107 cells | As above | 5 × 107 = 1 PR (2.9 m) 1 SD (2.1 m) 1 PD (2 m) 15 × 107 = 1 sCR (6.4 m) 1 sCR (4.8 m) 1 VGPR (4.4 m) 45 × 107 = 1 PR (3 m) 1 SD (2.5 m) 1 PR (1 m) |
67% Grade I/II | Neutropenia (89%), leukopenia (67%), anemia (44%) | [67] |
| Guo et al. (2015) Phase I | 5 | 5–8 | PCD, CP, VAD | CART-138 | CD28 ICD-CD3zeta | 0.44–1.51 × 107/kg | CD 138 (syndecan 1), neoplastic and Non-neoplastic plasma cells | 4 SD (3–7 m) 1 PD |
Not reported | 4 Grade III fever | [68] |
| Ramos et al. (2016) Phase I | 7 | ≥1 (2–8) | C | Kappa-CAR T cells | CD28 ICD-CD3zeta | 0.2–2 × 108/m2 | Kappa light chain, mature B cells | 4 SD 3 Not reported |
None | Grade III lymphopenia | [69] |
| Garfall et al. (2016) Pilot study | 12 | 6 | Not reported | CTL019 cells | 4-1BB ICD-CD3zeta | 1–5 × 107 cells Additional therapy: ASCT + Melphalan |
CD-19. Rarely on MM Plasma cells and cancer stem cell population | Median PFS = 6 m 1 CR 6 VGPR (3.2 m) 2 PD (3.2 m) 2 PR (3.2 m) |
1 Grade I | Grade 3 GVHD: n = 1; Grade 3 oral mucositis: n = 1 | [70] |
ASCT: Autologous stem cell transplantation; BCMA: B-cell maturation antigen; C: Cyclophosphamide; CART: Chimeric antigen receptor modified T cell; CF: Cyclophosphamide, fludarabine; CP: Carboplatin, paclitaxel; CR: Complete response; GVHD: Graft versus host disease; m: Month; MM: Multiple myeloma; MR: Minimal response; ORR: Overall response rate; PCD: Bortezomib, cyclophosphamide, dexamethasone; PD: Progressive disease; PFS: Progression-free survival; PR: Partial response; PRES: Posterior reversible encephalopathy syndrome; pt: Patient; REP: Response evaluable patient; sCR: Stringent complete response; SD: Stable disease; VAD: Vincristine, doxorubicin, dexamethasone; VGPR: Very good partial response; wk: Week.