CRS reported in recent clinical trials
| 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: 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
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