Managing cytokine release syndrome in hematological malignancies being treated with CAR-T therapy

INTRODUCTION: Cytokine release syndrome (CRS) is a potentially life-threatening toxicity associated with chimeric antigen receptor (CAR)-T cell therapy, particularly in hematological malignancies. As CAR-T therapies are increasingly integrated into clinical practice, managing CRS effectively is critical to maximizing therapeutic benefit while minimizing harm. AREAS COVERED: This review provides a comprehensive overview of CRS in the context of CAR-T therapy for hematologic cancers. It outlines the current definitions and grading systems, highlights key aspects of CRS pathophysiology, and analyzes the incidence and severity of CRS across pivotal clinical trials in large B-cell lymphoma, acute lymphoblastic leukemia, and multiple myeloma. Standard management approaches, including anti-cytokine therapies and corticosteroids, are discussed alongside emerging strategies such as early intervention and prophylaxis using anakinra and corticosteroids. The review is informed by a structured evaluation of clinical studies and real-world data, reflecting evolving treatment paradigms. EXPERT OPINION: CRS remains a major challenge, therefore early recognition, standardized grading, and targeted intervention will improve outcomes. Future efforts should focus on predictive biomarkers, personalized prophylaxis, and next-generation CAR constructs to reduce toxicity. The real-world experience mirrors trial data, reinforcing the reproducibility and scalability of these evolving management strategies.