Cytokine release syndrome in solid tumors

Cytokine release syndrome (CRS) is a common and potentially severe complication of cancer immunotherapy, including CAR T-cell therapies, bispecific T-cell engagers, and less commonly immune checkpoint inhibitors. Although extensive research has established guidelines for managing CRS in hematological malignancies, there is a growing need to address CRS in the context of solid organ tumors due to differences in tumor microenvironment, immunotherapy indications, and patient population. This review aims to provide an overview of CRS in solid tumors, outlining its pathophysiology, clinical presentation, and current management strategies. The complexities of CRS in solid tumors arise from challenges such as the immunosuppressive nature of the tumor microenvironment and the overlap of tumor-associated antigens with healthy tissues, potentially increasing the risk of severe on-target off-tumor toxicities. The review emphasizes early detection and grading of CRS as essential for patient safety and effective intervention. Management of CRS involves supportive care for mild cases, whereas severe presentations often require targeted therapies like tocilizumab, corticosteroids, and escalation to the intensive care unit for organ support. The decision to rechallenge or withhold immunotherapy requires careful consideration of patient-specific goals and risks. Emerging treatments such as other cytokine inhibitors, plasma exchange, and suicide gene systems are promising avenues for mitigating severe CRS. Future research focuses on refining risk stratification tools, novel therapeutic agents, and evaluating long-term outcomes. A deeper understanding of CRS in solid tumors will enable more personalized treatment approaches, enhancing the safety and efficacy of immunotherapies for this patient population.