Systematic Review of CAR-T Cell Therapy-Related Cytokine Release Syndrome Management Strategies

Abstract

Background: Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematologic malignancies; however, cytokine release syndrome (CRS) remains a frequent and potentially life-threatening complication. Effective management strategies are critical to optimizing patient outcomes while preserving therapeutic efficacy.

Objective: To systematically review current evidence on the management strategies of CAR-T–associated CRS, focusing on pharmacological and supportive interventions.

Methods: A systematic literature review was conducted using databases including PubMed, Scopus, and Web of Science. Studies evaluating CRS management strategies such as tocilizumab, corticosteroids, and emerging therapies were included. Data on efficacy, safety, and clinical outcomes were extracted and synthesized.

Results: Tocilizumab, an interleukin-6 (IL-6) receptor antagonist, is the cornerstone of CRS management and is FDA-approved for severe or life-threatening cases. Evidence suggests rapid symptom resolution in most patients following one or two doses. Corticosteroids are reserved for refractory or severe CRS but may affect CAR-T cell persistence. Emerging therapies such as anakinra and early combination strategies show promise in reducing severe CRS incidence. Supportive care remains essential across all CRS grades.

Conclusion: Current evidence supports a stepwise, severity-based approach to CRS management, with tocilizumab as first-line therapy and corticosteroids for refractory cases. Further randomized trials are needed to optimize treatment timing, combinations, and long-term outcomes.