Lost in translation: why cytokine release syndrome reporting fails clinical trials
- 1Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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.
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BibTeX
@article{champiat2026lost,
title = {{Lost in translation: why cytokine release syndrome reporting fails clinical trials}},
author = {Stephane Champiat},
journal = {Journal for Immunotherapy of Cancer},
year = {2026},
month = nov,
doi = {10.1136/jitc-2026-016598},
url = {https://doi.org/10.1136/jitc-2026-016598},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Lost in translation: why cytokine release syndrome reporting fails clinical trials
AU - Stephane Champiat
PY - 2026
DA - 2026/11/04
JO - Journal for Immunotherapy of Cancer
DO - 10.1136/jitc-2026-016598
UR - https://doi.org/10.1136/jitc-2026-016598
AB - 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.
SN - 2051-1426
ER -