Abstract
Introduction. Oncological diseases remain one of the leading causes of mortality worldwide. CAR T-cell therapy has demonstrated high efficacy in the treatment of B-cell leukaemias, lymphomas, and multiple myeloma. However, it is associated with a high risk of cytokine release syndrome, which occurs in approximately 55.3% of patients. The aim of the study is to analyse and synthesise current evidence on the pathophysiology of cytokine release syndrome, approaches to its diagnosis, risk stratification, and stepwise pharmacological management in patients undergoing CAR T-cell therapy, with particular emphasis on the key limitations of existing recommendations and promising directions for further research.
Materials and methods. A review of publications indexed in eLibrary, PubMed, and the Cochrane Library between 2016 and 2026 was conducted using the following keywords: CAR T-therapy, cytokine release syndrome, ferritin, IL-6, CRP, tocilizumab, anakinra, glucocorticoids, biomarkers, and ASTCT grading. The final review included 50 sources comprising original clinical studies, systematic reviews, meta-analyses, and consensus recommendations.
Results. To assess the severity of cytokine release syndrome, the consensus grading system developed by the American Society for Transplantation and Cellular Therapy is recommended; it distinguishes four grades of syndrome severity. Elevated serum ferritin, C-reactive protein, and IL-6 levels are considered the most informative predictors of severe cytokine release syndrome. Treatment is based on a stepwise approach, with tocilizumab and glucocorticoids used as first-line therapies; their dosing regimens are determined according to cytokine release syndrome severity. In refractory cases, the National Comprehensive Cancer Network recommends anakinra as the treatment of choice.
Discussion and conclusion. Cytokine release syndrome remains one of the major limiting factors for the widespread clinical use of CAR T-cell therapy. Although a stepwise approach to the management of patients with cytokine release syndrome is widely accepted, it is not without limitations. This review highlights the need to modify and improve current approaches to the diagnosis and treatment of cytokine release syndrome, particularly its refractory forms. In the authors’ view, further research should focus on optimising existing diagnostic and therapeutic strategies, identifying highly specific predictors of CAR T-cell therapy toxicity, developing comprehensive prognostic scoring systems to assess the risk of cytokine release syndrome, and investigating the molecular mechanisms underlying refractory disease in order to develop new therapeutic options.