Year: 2026
Type: editorial
Abstract: Cytokine release syndrome (CRS) is among the most frequently reported adverse events in trials of immune-cell-engaging therapies, yet its identification, grading, and reporting remain inconsistent across sponsors and investigators, driving overly conservative dose-escalation decisions, premature dose-limiting toxicity calls, unwarranted tocilizumab or corticosteroid use, and confounded cross-trial safety comparisons. Cytokine release symptoms, transient findings reflecting expected immune-cell engagement, are distinguished from CRS as a formal syndrome and from cytokine storm as its most severe manifestation. Current practice is associated with several pitfalls, including systematic exclusion of CRS-mimicking differential diagnoses, misclassification of grade 2 hypotension absent formal vasoplegia testing, the American Society for Transplantation and Cellular Therapy (ASTCT) framework’s failure to incorporate organ dysfunction beyond hypotension and hypoxia, and the frequent misattribution of isolated, self-limited transaminitis to severe CRS. While ASTCT remains the most practical standard available, closing these reporting gaps is essential for investigators, sponsors, and health authorities to ensure safety evaluation and decisions reflect genuine toxicity rather than expected pharmacology.
Author: Stephane Champiat
Institution: The University of Texas MD Anderson Cancer Center
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,490
OpenAlex ID: W7225233291