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Table 1 CRS reported in recent clinical trials

From: Cytokine release syndrome

Author/Year

Maude et al., 2018 [87]00

Park et al., 2018 [88] 00

Neelapu et al., 2017 [44] 00

Schuster et al., 2017 [89] 00

Turle et al., 2017

Gardner et al., 2017 [80] 8]

Ali et al., 2016 [79] 7]

Garfall et al., 2015 [90] 3]

Lee et al., 2015 [39] 5]

Maude et al., 2015 [32] 8]

Davila et al., 2014 [33] 9]

Kantarjian et al., 2017 [27] 4]

Stackelberg et al., 2016 [91] 5]

Topp et al., 2015 [68] 7]

Topp et al., 2014 [92] 6]

Institution

25 centers

MSKCC

22 centers

UPenn

FHCRC

SCHRI

NCI

UPenn

NCI

UPenn/UPhil

MSKCC

101 centers

26 centers

37 centers

9 centers

Applied therapy

CD19 CAR (4-1BB)

CD19 CAR (CD28)

CD19 CAR (CD28)

CD19 CAR (4-1BB)

CD19 CAR (4-1BB)

CD19 CAR (4-1BB)

BCMA CAR (CD28)

CD19 CAR (4-1BB)

CD19 CAR (CD28)

CD19 CAR (4-1BB)

CD19 CAR (CD28)

blinatumomab

blinatumomab

blinatumomab

blinatumomab

Disease

B-ALL

B-ALL

DLBCL/TFL/ PMBCL

DLBCL/TFL

CLL

B-ALL

MM

MM

B-ALL

B-ALL

B-ALL

B-ALL

B-ALL

B-ALL

B-ALL

Number of patients

75

53

101

28

24

45

12

11

20

30

16

267

70

189

36

Incidences

 % CRS

77

85

93

57

83

93

501

18

66

100

NR

14,2

11

NR

NR

 % sCRS (>°II)

46

26

13

18

8

23

171

9

32

27

44

4,9

5

3

0,8

 % sNeurotox (>°II)

13

42

28

11

25

21

0

NR

1

3

13

9,4

4

11

14

 treatment related deaths

12

13

34

15

16

0

0

0

0

0

0

37

68

19

310

sCRS correlates

 tumor burden

NR

y*

NR

NR

y

n

NR

NR

y

y

y

NR

NR

NR

y

 CRP/ferritin

n/y

NR

NR

NR

y*/y*

NR

NR

NR

y*/y*

y*11/y*

y*/NR

NR

NR

NR

NR

 IL-6/IFNg

y/y

NR

y/n

NR

y*/y*

y/NR

NR

NR

y*/y*

y*/y*

n*/n*

NR

NR

NR

NR

Therapy

 tocilizumab response

NR

NR

NR

1/1

5/6

NR

100

NR

50%12

100%

y

NR

NR

NR

NR

 steroid response

NR

NR

NR

0/0

5/6

NR

NR

NR

y

y

y

NR

NR

NR

NR

Prognosis

 CRS related to ORR?

NR

NR

NR

NR

NR

NR

NR

NR

y

NR

NR

NR

NR

2/3 CR

y

 tocilizumab related to reduced ORR?

NR

NR

n

n

NR

n

n

NR

n

possible13

n

NR

NR

NR

NR

 steroids related to reduced ORR?

NR

NR

n

NR

NR

n

NR

NR

n

possible13

y

NR

NR

NR

NR

Response

 % ORR

81

83

82

64

71

100

25

NR

33

10

NR

NR

45

52

75

 % CR (MRD -)

81 (81)

83 (6714)

55

57

17

93 (93)

8

NR

66 (62)

90

88 (75)

44

39 (20)

43 (32)

69 (61)

  1. 1: no definition of CRS supplied, but patients showed signs of CRS. 2: death due to cerebral hemorrhage in the context of coagulopathy and resolving cytokine release syndrome. 3: 1 death due to °V CRS before dose adjustment to disease burden. 4: 2 deaths attributed to CRS, 1 to pulmonary embolism. 5: 1 death due to neurotoxicity. 6:1 death to °V CRS with °V cerebral edema refractory to tocilizumab, siltuximab, dexamethasone before reduction of CAR T cell dose. 7: not further specified. 8: 6 fatal AEs attributed to blinatumomab, one due to °IV CRS with °V respiratory failure. 9: 1 death due to fungal infection of the brain after HSCT classified as possibly related to blinatumomab. 10: 3 deaths due to sepsis and candida infection classified as possibly related to blinatumomab. 11: CRP > 20 mg/dl: positive predictive value only 50%.12: 2 patients received steroids additional to tocilizumab for not reported reasons.13: 2 of 9 patients treated with immunosuppression (not further specified if related to tocilizumab or glucocorticoids) relapsed. 14: 48 patients evaluable. *: statistically significant
  2. B-ALL acute lymphoblastic B cell leukemia, CLL chronic lymphocytic leukemia, DLBCL diffuse large B cell lymphoma, MM Multiple myeloma, MPM malignant pleural mesotheliomas, NR not reported, PDA pancreatic ductal adenocarcinoma, PMBCL primary mediastinal large B-cell lymphoma, TFL transformed follicular lymphoma, sNeurotox severe neurotoxicity