Table 1.
Selected clinical trials of CAR T cell therapy in relapsed/refractory multiple myeloma (published as manuscript or abstract).
| Target | Identifier | Product | Phase | N | LDC | Dose (cells/kg) | Prior lines of therapy | ORR | Median PFS | Toxicity | Management of CAR T cell therapy associated toxicities | Ref |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| BCMA | NCT02215967 | CAR-BCMA | 1 | 24 | Cy/Flu | 0.3–9 × 106 | 9.5 | 81%# | 31 weeks | CRS (≥G3) = 6 pts, CRS (G1–2) = 7 pts, cytopenia (≥G3) = 15 pts, severe NT = 1 pt |
tocilizumab in 5 pts, corticosteroids in 4 pts |
(38) |
| 1 | 12 | Cy/Flu | 0.3–9 × 106 | 7 | 100%# | NR | cytopenia (≥G3) = 12 pts, CRS (all Gs) = 6 pts |
tocilizumab in 2 pts | (55) | |||
| NCT02546167 | CART-BCMA | 1 | 25 | Cy or none | cohorts 1 and 3: 1–5 × 108, cohort 2: 1–5 × 107 |
7 | cohort 1: 44%, cohort 2: 20%, cohort 3: 64% |
cohort 1: 65 days, cohort 2: 57 days, cohort 3: 125 days |
CRS (all Gs) = 88%, NT = 32% |
tocilizumab in 6 pts, siltuximab in 1 pt |
(41) | |
| NCT02658929 | bb2121 | 1 | 33 | Cy/Flu | 50×, 150×, 450×, or 800×106 | 7–8 | 85% | 11.8 months | neutropenia (≥G3) = 85%, CRS (all Gs) = 76%, CRS (≥G3) = 6%, NT (all Gs) = 42%, NT (G4) = 3% |
tocilizumab in 7 pts, corticosteroids in 4 pts |
(39) | |
| NCT03090659 | LCAR-B38M | 1 | 57 | Cy | 0.07–2.1 × 106 | 3 | 88% | 15 months | leukopenia (≥G3) = 30%, CRS (all Gs) = 90%, CRS (≥G3) = 7%, NT (G1) = 2% |
tocilizumab in 26 pts | (42) | |
| 1 | 17 | Cy/Flu or Cy | 0.21–1.52 × 106 | 4 | 88% | 12 months | CRS (G1–2) = 59%, CRS (≥G3) = 41%(1G5) cytopenias (all Gs) = 82% |
tocilizumab in 10 pts (with additional etanercept in 2 pts) | (40) | |||
| NCT03430011 | JCARH125 | 1/2 | 19 | Cy/Flu | 50 × 106 or 150 × 106 | 10 | 100% | NR | CRS (G1–2) = 6 pts, N T(all Gs) = 3 pts, sepsis after LDC (G5) = 1 pt |
tocilizumab in 1 pt, corticosteroids in 1 pt |
(56) | |
| 1/2 | 51 | Cy/Flu | 300×, 450×, or 600×106 | 6 | 91% | NR | CRS (G ≥ 3) = 2%, NT (G ≥ 3) = 4%, infection (G ≥ 3) = 14%, |
tocilizumab and/or corticosteroids in 40 pts, anakinra in 7 pts |
(57) | |||
| NCT03070327 | MCARH171 | 1 | 11 | Cy/Flu or Cy | 72×, 137×, 475×, or 818 × 106 | 6 | 64% | NR | CRS (G1–2) = 40%, CRS (G3) = 20%, NT (G2) = 10% |
tocilizumab in 3 pts | (58) | |
| NCT03338972 | FCARH143 | 1 | 7 | Cy/Flu | 5× or 15 × 107 | 8 | 100% | NR | CRS (G1–2) = 86% | NR | (13) | |
| NCT03288493 | P-BCMA-101 | 1/2 | 25 | Cy/Flu | 0.5–5 × 108 | 7 | 48% | NR | CRS (G ≥ 3) = 32%, NT (G ≥ 3) = 12% |
NR | (59) | |
| NCT03274219 | bb21217 | 1 | 22 | Cy/Flu | 150, 450, 800, or 1200 × 106 | 7 | 83% | NR | CRS = 59% (5G1, 7G2,1G3), NT = 23% (1G1, 2G2,1G3,1G4) |
tocilizumab and/or corticosteroids | (60) | |
| NCT03548207 | JNJ-68284528 | 1b/2 | 29 | Cy/Flu | median 0.73 × 106 | 5 | 100% | NR | neutropenia (G ≥ 3) = 100%, CRS = 93% (25G1–2,1G3,1G5), NT = 14% (3G1–2,1G3) |
NR | (61) | |
| NCT03361748 | bb2121 | 2 | 128 | Cy/Flu | 150–450 × 106 | 6 | 73% | 8.6 months | cytopenias(all Gs) = 97%, CRS(all Gs) = 84%(5G3,1G4,1G5), NT(G3) = 18% |
NR | (62) | |
| NCT03661554 | NR | 1 | 16 | Cy/Flu | 2–10 × 106 | NR | 100% | NR | CRS (G3–4) = 2 pts, CRS (G0–2) = 14 pts |
NR | (63) | |
| NCT03093168 | NR | 1 | 46 | Cy/Flu | 9 × 106 | NR | 79.6% | 15 months | CRS (G1–2) = 22.7%, CRS (G3) = 6.8% |
NR | (64) | |
| NCT03716856 NCT03302403 NCT03380039 | CT053 | 1 | 24 | Cy/Flu | 1.5×, 0.5×, 1×, or 1.8 × 108 | 4.5 | 87.5% | NR | leukopenia (G ≥ 3) = 87.5%, CRS(G1–2) = 62.5% (3G1,12G2), NT = 12.5% (2G1,1G3), neutropenic infection (G5) = 1 pt |
tocilizumab in 8 pts | (65) | |
| CD138 | NCT01886976 | CART-138 | 1/2 | 5 | PCD/CP/VAD | median 0.756 × 107 | 10 | 0% | NR | fever (G3) = 80% | NR | (66) |
| CD19 | NCT02135406 | CTL019 | 1 | 10 | Mel + ASCT | 1–5 × 107 | 6 | 90% | 200 days | CRS (G1) = 1 pt, GvHD (G3) = 1 pt, mucositis (G3) = 1 pt |
NR | (67) |
| NKG2D | NCT02203825 | CM-CS1 | 1 | 5 | None | 1 × 106–3 × 107 | ≥5 | 0% | NR | no CRS, no NT, no treatment related toxicity (G ≥ 3) |
NR | (50) |
| kappa light chain | NCT00881920 | κ.CART | 1 | 7 | Cy or none | 0.92–1.9 × 108/m2 | 4 | 0% | NR | no CRS | NR | (46) |
| BCMA and CD19* | NCT03196414 | NR | 1/2 | 28 | Cy/Flu | BCMA: 2–6.8 × 107, CD19: 1 × 107 |
3 | 92.6% | 8 months | CRS (G1–2) = 19 pts, CRS (G3) = 7 pts, CRS (G4) = 2 pts, NT (G4) = 1 pt, |
NR | (68) |
| BCMA and CD19* | NCT03455972 | NR | 1/2 | 32 | BuCy or Mel + ASCT | CD19: 1 × 107, BCMA: NR |
NR | 100% | NR | CRS (G1–2) = 31 pts, CRS (G3) = 1 pt |
tocilizumab in 1 pt | (69) |
| BCMA and CD19* | ChiCTR-OIC-17011272 | NR | 2 | 22 | Cy/Flu | CD19: 1 × 106, BCMA: 1 × 106 |
6 | 95% | VGPR: 243 days, sCR: 268 days |
CRS (G1–2) = 18 pts, CRS (G ≥ 3) = 1 pt, cytopenias (all Gs) = 20 pts, NT (all Gs) = 2 pts, cerebral hemorrhage (G5) = 1 pt |
NR | (70) |
| BCMA/CD38ǂ | ChiCTR180001814 | BM38 | 1 | 16 | Cy/Flu | 0.5×, 1.0×, 2.0×, 3.0× or 4.0× 106 | NR | 87.5% | NR | CRS (G1–2) = 10 pts, CRS G ≥ 3) = 4 pts |
tocilizumab in 4 pts | (51) |
| BCMA/CD19ǂ | NR | NR | NR | 5 | Cy/Flu | 1.0×106 or 2.0×106 | 3 | 100% | NR | CRS (G1) = 3 pts | NR | (54) |
| BCMA/TACIǂ | NCT03287804 | AUTO2 | 1/2 | 12 | Cy/Flu | 15×, 75×, 225×, 600× or 900× 106 | 5 | 43% | NR | anemia (G ≥ 3) = 82%, neutropenia (G ≥ 3) = 73%, CRS (all G1) = 45% |
tocilizumab in 3 pts | (53) |
ASCT, autologous stem cell transplant; BCMA, B cell maturation antigen; Bu, busulfan; CAR T cell, chimeric antigen receptor modified T cell; CP, chlorambucil, prednisone; CRS, cytokine release syndrome; Cy, cyclophosphamide; Flu, fludarabine; G, grade; LDC, lymphodepleting conditioning; Mel, melphalan; NR, not reported; NT, neurotoxicity; ORR, overall response rate; PCD, pomalidomide, cyclophosphamide, dexamethasone; PFS, progression-free survival; pt, patient; Ref, reference; sCR, stringent complete remission; TACI, transmembrane activator and calcium modulator and cyclophilin ligand interactor; VAD, vincristine, doxorubicin, dexamethasone; VGPR, very good partial remission.
#In patients with the highest dose.
*The patients received both BCMA and CD19 directed CAR T cells.
ǂBispecific CAR T cells.