Table 1.
Multiple myeloma CAR-T-cell clinical trials targeting BCMA
| Trial # ref. (product name) | n = | Origin mAb | Expansion | Loading | Co-stimulation | T-cell dosage | Conditioning | Toxicity | Clinical response |
|---|---|---|---|---|---|---|---|---|---|
| ChiCTR-OIC17011272 [27] (CD19 & BCMA CAR-T) | 21 | Murine scFv | aCD3 | Lentiviral | 4-1BB | 1 × 106/kg | CP/Flu |
CRS gr. 1–2 (86%), gr. ≥ 3 (5%) Neurotoxicity (10%) |
sCR/CR (57%)/VGPR (24%) PR (14%) |
| NCT02658929 [24, 28] (bb2121) | 43/39 | Murine scFv | aCD3 + aCD28 | Lentiviral | 4-1BB | 50–800 × 106 | CP/Flu |
CRS gr. 1–2 (58%), gr. ≥ 3 (5%) Neurotoxicity (33%) |
sCR/CR (44%)/VGPR (23%) PR (10%) |
| NCT03274219 [29] (bb21217) | 38 | Murine scFv |
aCD3 + aCD28 + PI3k inhibitor |
Lentiviral | 4-1BB | 150–450 × 106 | CP/Flu |
CRS gr. 1–2 (61%), gr. ≥ 3 (5%) Neurotoxicity (24%) |
sCR/CR (13%)/VGPR (34%) PR (5%) |
| ChiCTR-OPC16009113 [30, 31] (BCMA-CAR T) | 28 | Murine scFv | aCD3 | Lentiviral | CD28/4-1BB | 5.4–25 × 106/kg | CP/Flu | CRS gr. ≥ 3 (14%) |
sCR/CR (61%)/VGPR (4%) PR (21%) |
| NCT02215967 (1) [25, 32] (NCI BCMA CAR-T) | 10 | Murine scFv |
aCD3 + IL-2 |
Retroviral | CD28 | 0.3–3 × 106/kg | CP/Flu | CRS gr. 1–2 (30%) |
VGPR (10%) PR (10%) |
| NCT02215967 (2) [25] (NCI BCMA CAR-T) | 16 | Murine scFv |
aCD3 + IL-2 |
Retroviral | CD28 | 9 × 106/kg | CP/Flu |
CRS gr. 1–2 (56%), gr. ≥ 3 (38%) Neurotoxicity (6%) |
sCR/CR (13%)/VGPR (50%) PR (19%) |
| ChiCTR-1800018143 [33] (BM38 CAR) | 22 | Humanized scFv | ND | ND | 4-1BB | 0.5–4 × 106/kg | CP/Flu | CRS gr. 1–2 (68%), gr. ≥ 3 (23%) |
sCR/CR (55%)/VGPR (9%) PR (24%) |
| NCT02546167 [20] (CART-BCMA UPenn) | 25 | Human scFv | aCD3/CD28 | Lentiviral | 4-1BB | 50–500 × 106 | CP or none |
CRS gr. 1–2 (56%), gr. ≥ 3 (32%) Neurotoxicity (32%) |
sCR/CR (8%)/VGPR (20%) PR (20%) |
| NCT03302403, NCT03380039, NCT03716856 [34, 35] (CT053) | 24 | Human scFv | aCD3/CD28 | Lentiviral | 4-1BB | 50–180 × 106 | CP/Flu |
CRS gr. 1–2 (63%) Neurotoxicity (8%) |
sCR/CR (79%)/VGPR (4%) PR (4%) |
| NCT03430011 [36] (JCARH125) | 44 | Human scFv | ND | Lentiviral | 4-1BB | 50–450 × 106 | CP/Flu |
CRS gr. 1–2 (70%), gr. ≥ 3 (9%) Neurotoxicity (25%) |
sCR/CR (27%)/VGPR (20%) PR (34%) |
| NCT03815383 [37] (C-CAR088) | 5 | Human scFv | ND | Lentiviral | 4-1BB | 1–3 × 106/kg | CP/Flu | CRS gr. 1–2 (80%) |
sCR/CR (20%)/VGPR (60%) PR (20%) |
| ChiCTR-1800018137 [38] (CT103A) | 18 | Human scFv | ND | Lentiviral | 4-1BB | 1–6 × 106/kg | CP/Flu | CRS gr. 1–2 (72%), gr. ≥ 3 (22%) |
sCR/CR (67%)/VGPR (17%) PR (17%) |
| NCT03549442 [39] (CART-BCMA + CTL119) | 16 | Human scFv | ND | Lentiviral | 4-1BB | 500 × 106 | CP/Flu | CRS gr. 1–2 (88%) |
sCR/CR (19%)/VGPR (25%) PR (25%) |
| NCT03338972 [40] (FCARH143) | 11 | Human scFv | aCD3/CD28 | Lentiviral |
4-1BB + EGFRt |
50–150 × 106 | CP/Flu |
CRS gr. 1–2 (91%) Neurotoxicity (9%) |
sCR/CR (55%)/VGPR (36%) PR (9%) |
| NCT03502577 [41] (FCARH143 + GSI) | 10 | Human scFv | ND | Lentiviral |
4-1BB + EGFRt |
50–300 × 106 | CP/Flu |
CRS gr. 1–2 (60%), gr. ≥ 3 (40%) Neurotoxicity (60%) |
sCR/CR (30%)/VGPR (50%) PR (20%) |
| NCT03196414 [42] (SZ-MM-CART01) | 29/28 | Humanized scFv | aCD3 | Lentiviral | CD28/OX40 | 20–82 × 106/kg | CP/Flu |
CRS gr. 1–2 (66%), gr. ≥ 3 (34%) Neurotoxicity (3%) |
sCR/CR (54%)/VGPR (4%) PR (29%) |
| NCT03455972 [43] (SZ-MM-CART02) | 32 | Humanized scFv | aCD3 | Lentiviral | CD28/OX40 | 50 × 106/kg |
BUCY or Mel + autoHSCT |
CRS gr. 1–2 (97%), gr. ≥ 3 (3%) |
sCR/CR (72%)/VGPR (ND) PR (ND) |
| NCT03070327 [26] (MCARH171) | 10/11 | Human scFv | ND | Retroviral |
4-1BB + EGFRt |
1 × 106/kg or 150–450 × 106 |
CP/Flu or CP |
CRS gr. 1–2 (40%), gr. ≥ 3 (20%) Neurotoxicity (10%) |
VGPR (45%) PR (18%) |
| NCT03602612 [44] (FHVH33) | 15 | Human VH | ND | Retroviral | 4-1BB | ND | CP/Flu |
CRS gr. 1–2 (87%), gr. ≥ 3 (7%) Neurotoxicity (27%) |
sCR/CR (20%)/VGPR (7%) PR (53%) |
| NCT03288493 [45] (P-BCMA-101) | 23/19 | Human centyrin | None | Transposon |
4-1BB + rimiducid SS |
51–1143 × 106 | CP/Flu |
CRS gr. 1–2 (9%) Neurotoxicity (4%) |
sCR/CR + VGPR (26%) PR (42%) |
| NCT03661554 [46] (BCMA nanoantibody) | 9 | Alpaca VHH | ND | Lentiviral | 4-1BB | 250–900 × 106 | CP/Flu |
CRS gr. 1–2 (67%), gr. ≥ 3 (22%) Neurotoxicity (11%) |
sCR/CR (56%)/VGPR (33%) PR (11%) |
| NCT03090659 (1) [47, 48] (LCAR-B38M) | 17 | Llama VHH |
aCD3/CD28 + IL-2 |
Lentiviral | 4-1BB | 0.21–1,52 × 106/kg | CP/Flu or CP | CRS gr. 1–2 (59%), gr. ≥ 3 (41%) | sCR/CR (82%)/VGPR (6%) |
| NCT03090659 (2) [49, 50] (LCAR-B38M) | 57 | Llama VHH |
aCD3/CD28 + IL-2 |
Lentiviral | 4-1BB | 0.07–2,1 × 106/kg | CP |
CRS gr. 1–2 (82%), gr. ≥ 3 (7%) Neurotoxicity (2%) |
sCR/CR (73%)/VGPR (4%) PR (11%) |
| NCT03548207 [51] (LCAR-B38M) | 29 | Llama VHH | ND | Lentiviral | 4-1BB | 0.5–0.9 × 106/kg | CP/Flu |
CRS gr. 1–2 (86%), gr. ≥ 3 (7%) Neurotoxicity (10%) |
sCR/CR (69%)/VGPR (17%) PR (14%) |
| ChiCTR-1800017404 [52] (BCMA CAR-T) | 33/32 | ND | ND | Lentiviral | 4-1BB | 1–6 × 106/kg | CP/Flu | CRS gr. 1–2 (52%), gr. ≥ 3 (48%) |
sCR/CR (66%)/VGPR (22%) PR (13%) |
| NCT03093168 [53] (HRAIN BCMA-CART) | 49 | ND | ND | Retroviral |
4-1BB + EGFRt |
9 × 106/kg | CP/Flu | CRS gr. 1–2 (12%), gr. ≥ 3 (6%) |
sCR/CR (45%)/VGPR (18%) PR (14%) |
| ChiCTR-1900027678 [54] (GC012F) | 5 | ND | ND | ND | ND | 1–2 × 106/kg | CP/Flu or none | CRS gr. 1–2 (80%) | sCR/CR (20%)/VGPR (80%) |
| Pooled studies | 639/630 | CRS gr. 1–4 (80.3%) | ORR (80.5%) | ||||||
| (95% CI 69.0–88.2; I2 = 83%) | (95% CI 73.5–85.9; I2 = 61%) | ||||||||
| Neurotoxicity (10.5%) | |||||||||
| (95% CI 6.8–16.0; I2 = 58%) |
aCD3 + aCD28 = anti-CD3 and anti-CD28 antibodies. aCD3/CD28 + IL-2 = anti-CD3 and anti-CD28-coated beads plus interleukin-2. AutoHSCT = autologous hematopoietic stem cell transplant. BCMA = B-cell maturation antigen. BUCY = busulfan and cyclophosphamide. CAR = chimeric antigen receptor. CP = cyclophosphamide. CR = complete response. CRS = cytokine release syndrome. EGFRt = truncated epidermal growth factor receptor. Flu = fludarabine. Gr. = grade. GSI = gamma-secretase inhibitor. IL-2 = interleukin-2. Mel = melphalan. n = number of patients evaluable for toxicity/clinical response. ND = not disclosed. PI3k = phosphoinositide 3-kinase. PR = partial response. scFv = single-chain fragment variable. SS = safety switch. sCR = stringent complete response. Trial # = study registration number in Clinicaltrials.gov (NCT#) or Chinese Clinical Trial Registry (ChiCTR-#). VGPR = very good partial response. VHH = nanobody