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Table 1 Selected published clinical trials of CAR T-cell therapy

From: Mechanisms of cytokine release syndrome and neurotoxicity of CAR T-cell therapy and associated prevention and management strategies

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]

  1. 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
  2. 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
  3. * Severe CRS/ICANS are defined as CRS/ICANS ≥ Grade 3
  4. † Modified criteria
  5. ‡ 25 m 50% vs 6.3 m 50% (Cy/Flu Group vs Cy or Cy/E Group)
  6. § Progression-free survival
  7. ¶ Event-free survival