CRS characterization
| Characteristic, median (range) | Patients with CRS (N=108) |
| Time to onset, days | 3 (1–22) |
| Time from onset of CRS to grade 4 CRS, days | 4.5 (1–18) |
| Duration, days | |
| Any grade CRS | 8 (1–36) |
| Grade 3/4 CRS | 10 (4–36) |
| Fever ≥38.6°C, n (%) | 103 (95) |
| Time to onset, days | 3 (1–22) |
| Duration, days | 6 (1–36) |
| ICU admission, n (%) | 58 (54) |
| Time to ICU admission, days | 6 (1–24) |
| Duration of ICU stay, days | 7.5 (1–66)* |
| Anticytokine therapy, n (%)† | 44 (41) |
| Tocilizumab | 43 (40) |
| 1 dose | 23 (21) |
| 2 doses | 14 (13) |
| 3 doses | 6 (6) |
| Corticosteroids | 25 (23) |
| Siltuximab | 5 (5) |
| Other | 7 (6) |
| Hypotension that required intervention, n (%) | 60 (56) |
| High-dose vasopressors, n (%)‡ | 33 (31) |
| Oxygen supplementation, n (%) | 54 (50) |
| Intubation, n (%) | 18 (17) |
| Duration of intubation, days | 8 (4–26) |
| Dialysis, n (%)§ | 12 (11) |
| Duration of dialysis, days | 13.5 (2–61) |
| Fibrinogen <1.0 g/L, n (%) | 9 (8) |
| Outcome, n (%) | |
| Recovered/resolved | 106 (98)¶ |
| Not recovered/resolved | 2 (2)** |
Only the first CRS episode is summarized for each patient. Data are median (range) unless otherwise specified.
*Excluding outliers (ie, one patient with an ICU stay of 66 days), median (range) is 7 (1–34) days.
†Administered per the protocol-specific CRS management algorithm (online supplemental table 1). 24 of the 25 patients who received corticosteroids also received tocilizumab. All five patients who received siltuximab also received tocilizumab and corticosteroids. Of the seven patients who received ‘other’ anticytokine therapy, all experienced grade 4 CRS and received etanercept in addition to tocilizumab and corticosteroids, two also received siltuximab, and one also received infliximab.
‡High-dose vasopressors (defined in the University of Pennsylvania grading scale21 22) included vasopressin, norepinephrine, dopamine, phenylephrine, and epinephrine.
§Patients were dialyzed during CRS to manage fluid overload and/or acute kidney injury with only five patients having grade 3/4 creatinine elevation.
¶In one patient, CRS resolved, but the patient died due to HHV-6 encephalitis.
**Both patients died due to leukemia progression with CRS ongoing.
CRS, cytokine-release syndrome; HHV-6, human herpesvirus-6; ICU, intensive care unit.