Table 2.
Cytokine release syndrome and neurological toxicity in prominent CD19-targeted CAR T-cell therapeutic trials to date
| Institution | Patient populations | CRS incidence and severity | CRS grading | CRS-specific management | Neurological toxicity* |
|---|---|---|---|---|---|
| CHOP3,4 | Pediatric ALL | 25/25 with any CRS (initial cohort); 8/25 required vasopressors 48/53 with ≥grade 1 CRS (most updated) | UPenn | Toci (28%) ± CS (n = 9); reversed in all cases | 13/25 (initial cohort), ranging from delirium to global encephalopathy (aphasia, seizures, hallucinations); reversed in all cases |
| NCI5 | Pediatric ALL | 15/20 with ≥grade 1 CRS (grade 3, n = 3; grade 4, n = 3); 1 patient with cardiac arrest | NCI | Toci alone (n = 2); Toci + CS (n = 2) | 6/20, including visual hallucinations (n = 5) and transient dysphasia (n = 1) |
| NCI7 | Adult B-NHL | 12/15 (fever); 4/15 (hypotension) | NFG | Toci (n = 2) | 6/15, including confusion, obtundation, aphasia, encephalopathy |
| MSKCC8-10 | Adult ALL | 11/46 with severe CRS (requiring vasopressors or mechanical ventilation) | NFG | Not formally reported | 13/46 with ≥grade 3 neurological toxicity |
| FHCRC11 | Adult ALL | 7/27 with severe CRS (fever/hypotension requiring ICU care); fatal in 2 patients | NFG | Not formally reported | 13/27 with ≥grade 3 neurological toxicity |
| FHCRC12 | Adult CLL and B-NHL | 0/12 with severe CRS (Cy cohort) 2/16 with DLT (Cy + Flu cohort) | NFG | Not formally reported | Not formally reported |
| UPenn13 | Adult CLL | 9/14 with ≥grade 1 CRS (grade 3-4, n = 6; ICU admission, n = 4) | UPenn | Toci and/or CS (n = 5) | 6/14, including ≤grade 2 hallucinations, confusion, delirium (n = 5) and grade 4 confusion (n = 1) |
| UPenn14 | Adult CLL | 14/26 with any CRS | NFG | Toci ± CS (n = 3) | Not formally reported |
| UPenn15 | Adult B-NHL | 16/24 with any CRS (grade 2, n = 14; grade 3, n = 1; grade 4, n = 1) | UPenn | Not formally specified | 3/24, including delirium (grade 2, n = 1; grade 3, n = 1), and encephalitis (grade 5, n = 1) |
| UPenn14 | Adult ALL | 11/12 with ≥grade 3 CRS; 3 patients with refractory/fatal CRS | UPenn | Toci alone (n = 6); Toci + CS (n = 2); Toci + siltuximab + CS (n = 1) | Not formally reported |
CS, corticosteroid; DLT, dose-limiting toxicity; ICU, intensive care unit; NFG, not formally graded; Toci, tocilizumab.
*
Graded by Common Terminology Criteria for Adverse Events v4.0.