Table 1.
Selected published clinical trials of CAR T-cell therapy
| Trial | N | Target | Costimu-latory domain | CR (%) | Overall survival rate | CRS and ICANS grading criteria | CRS (%) | Severe CRS* (%) | ICANS (%) | Severe ICANS* (%) | Toxicity related mortality | Refs |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ALL | ||||||||||||
| Maude et al. 2014 | 30 | CD19 | 4-1BB | 27(90) | 78% (6 m) | CTCAE† | 30(100) | 8(27) | 13(43) | NR | 0 | [31] |
| Lee et al. 2015 | 20 | CD19 | CD28 | 14(70) | 50% (12 m) | CTCAE† | 16(80) | 6(30) | 6(30) | 1(5) | 0 | [30] |
| Turtle et al. 2016 | 30 | CD19 | 4-1BB | 27(93) | NR | CTCAE† | 25(83) | 7(23) | 15(50) | 15(50) |
1 CRS 1 ICANS |
[84] |
| Gardner et al. 2017 | 43 | CD19 | 4-1BB | 40(93) | 69.5% (12 m) | CTCAE† | 40(93) | 10(23) | 21(49) | 9(21) | 0 | [205] |
| Maude et al. 2018 | 75 | CD19 | 4-1BB | 61(81) | 76% (12 m) |
PENN/CHOP CTCAE |
58(77)P | 35(46) | 30(40)C | 10(13) | 1 ICANS | [206] |
| Park et al. 2018 | 53 | CD19 | CD28 | 44(83) | 50% (12.9 m) |
MSKCC CTCAE |
45(85)M | 14(26) | 23(44)C | 22(42) | 1 CRS | [117] |
| Frey et al. 2020 | 35 | CD19 | 4-1BB | 24(69) | 50% (19.1 m) |
PENN/CHOP CTCAE |
33(94)P | 6(17) | 14(40)C | 2(6) | 3 CRS | [109] |
| Fry et al. 2018 | 21 | CD22 | 4-1BB | 12(57) | NR | CTCAE† | 16(76) | 0(0) | 6(28) | 0(0) | 0 | [80] |
| Shah et al. 2020 | 58 | CD22 | 4-1BB | 40(70) | 50% (13.4 m) |
Lee CTCAE ASTCT |
50(86)L |
5(10)L 12(24)A |
19(33)C | 1(2) | 0 | [81] |
| NHL | ||||||||||||
| Turtle et al. 2016 | 32 | CD19 | 4-1BB | 11(34) | ‡ | CTCAE† | 20(63) | 4(13) | 9(28) | 9(28) | 1 ICANS | [85] |
| Schuster et al. 2017 | 28 | CD19 | 4-1BB | 16(57) | 57% (28.6 m)§ |
PENN/CHOP CTCAE |
16(57)P | 5(18) | 11(39)C | 3(11) | 1 ICANS | [87] |
| Neelapu et al. 2017 | 101 | CD19 | CD28 | 55(54) | 52% (18 m) |
Lee CTCAE |
94(93)L | 13(13) | 65(64)C | 28(28) | 2 CRS | [89] |
| Schuster et al. 2019 | 111 | CD19 | 4-1BB | 37(40) | 50% (12 m) |
PENN/CHOP CTCAE |
64(58)P | 24(22) | 23(21)C | 13(12) | 0 | [118] |
| Abramson et al. 2020 | 269 | CD19 | 4-1BB | 136(53) | 58% (12 m) |
Lee CTCAE |
113(42)L | 6(2) | 80(30)C | 27(10) | 0 | [207] |
| MCL | ||||||||||||
| Wang et al. 2020 | 68 | CD19 | CD28 | 40(67) | 83% (12 m) |
Lee CTCAE |
62(91)L | 10(15) | 43(63)C | 21(31) | 0 | [208] |
| MM | ||||||||||||
| Brudno et al. 2018 | 16 | BCMA | CD28 | 10(63) | 50% (7.1 m)¶ | Lee | 15(94)L | 6(38) | NR | NR | NR | [209] |
| Zhao et al. 2018 | 57 | BCMA | 4-1BB | 39(68) | 50% (15 m)§ |
Lee CTCAE |
51(90)L | 4(7) | 1(2)C | 0(0) | NR | [210] |
| Cohen et al. 2019 | 25 | BCMA | 4-1BB | 2(8) | 50% (502d) |
PENN/CHOP CTCAE |
22(88)P | 8(32) | 8(32)C | 3(12) | 0 | [211] |
| Raje et al. 2019 | 33 | BCMA | 4-1BB | 15(45) | 50% (11.8 m)§ |
Lee CTCAE |
25(76)L | 2(6) | 14(42)C | 1(3) | 0 | [212] |
| Munshi et al. 2021 | 128 | BCMA | 4-1BB | 42(33) | 78% (12 m) |
Lee CTCAE |
107(84)L | 7(5) | 23(18)C | 4(3) | 1 CRS | [213] |
| CLL | ||||||||||||
| Porter et al. 2015 | 14 | CD19 | 4-1BB | 4(29) | 50% (29 m) | CTCAE† | 9(64) | 6(43) | 6(43) | 1(7) | 0 | [214] |
| Turtle et al. 2017 | 24 | CD19 | 4-1BB | 4(21) | 50% (6.6 m) |
Lee CTCAE† |
20(83)L | 2(8) | 8(33)C† | 6(25) | 1 CRS and ICANS | [86] |
| Frey et al. 2020 | 38 | CD19 | 4-1BB | 9(28) | 50% (64 m) |
PENN/CHOP CTCAE ASTCT |
24(63)P 23(59)A |
9(24) 4(11) |
3(8)C | 0(0) | 0 | [215] |
CAR Chimeric antigen receptor, N number of patients, CR Complete remission, CRS Cytokine release syndrome, ICANS Immune effector cell-associated neurotoxicity syndrome, Refs References, ALL Acute lymphoblastic leukemia, NHL Non-Hodgkin lymphoma, MCL Mantle cell lymphoma, MM Multiple myeloma, CLL Chronic lymphocytic leukemia, NR No report, m Months, d Days, h Hours, Cy Cyclophosphamide, Flu Fludarabine, E Etoposide
CRS and ICANS grading systems used by each trial are denoted by superscripts as follows: A ASTCT criteria, C CTCAE criteria, L Lee criteria, P PENN/CHOP criteria, M MSKCC criteria
* Severe CRS/ICANS are defined as CRS/ICANS ≥ Grade 3
† Modified criteria
‡ 25 m 50% vs 6.3 m 50% (Cy/Flu Group vs Cy or Cy/E Group)
§ Progression-free survival
¶ Event-free survival