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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