Table 1 Multiple myeloma CAR-T-cell clinical trials targeting BCMA

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 V_HH

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 V_HH

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 V_HH

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 V_HH

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%)