Need for Standardization of Cytokine Profiling in CAR T-Cell Therapy

With expansion of CAR T-cell therapy and broader utilization of anti-cytokine directed therapeutics for toxicity mitigation, the routine assessment of cytokines may enhance understanding of toxicity profiles, guide therapeutic interventions, and facilitate cross-trial comparisons. As specific cytokine elevations can correlate with and provide insights into CAR T-cell toxicity, mitigation strategies, and response, we explored the reporting of cytokine detection methods and assessed for the correlation of cytokines to CRS and ICANS across clinical trials. In this analysis we reviewed 21 clinical trials across 60 manuscripts that featured a Food and Drug Administration-approved CAR T-cell construct or one of its predecessors. We highlight substantial variability and limited reporting of cytokine measurement platforms and panels used across CAR T-cell clinical trials. Specifically, across 60 publications, 28 (46.7%) did not report any cytokine data, representing 6 of 21 (28.6%) clinical trials. In the 15 trials reporting cytokine data, at least 4 different platforms were used. Furthermore, correlation of cytokines with ICANS, CRS, and CRS severity was limited. Considering the fundamental role of cytokines in CAR T-cell toxicity our manuscript supports the need to establish standardization of cytokine measurements as a key biomarker essential to improving outcomes of CAR T-cell therapy.