Review Article - Journal of Cancer Immunology & Therapy (2024) Volume 7, Issue 6
Incidence and management of Cytokine release syndrome in CAR-T cell therapy for solid tumors: A systematic review of phase I trials.
Background: Chimeric Antigen Receptor T-cell (CAR-T) therapy has revolutionized treatment for hematologic cancers by genetically modifying T-cells to target cancer antigens, providing hope for patients with relapsed or refractory disease. The FDA approved second-generation CARs, like Kymriah and Yescarta, in 2017. However, applying CAR-T therapy to solid tumors presents challenges, including tumor heterogeneity and an immunosuppressive microenvironment. Toxicities such as Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) require careful management. Objectives: This systematic review aims to analyze CRS associated with CAR-T therapy in solid tumors. Key objectives include: • Evaluation of CRS: Assessthe incidence, severity, and clinical manifestations of CRS in solid tumors compared to hematologic malignancies. • Management Strategies: Evaluate the effectiveness of existing CRS management strategies and identify modifications needed for solid tumors. • Biomarker Exploration: Investigate the applicability of current biomarkers for predicting CRS in solid tumors and the potential need for novel biomarkers. • CAR-T Design Optimization: Compile findings to inform CAR-T cell design aimed at minimizing CRS risk and severity. Results: The review analysed data from 217 patients across Phase I clinical trials targeting solid tumors like colorectal cancer and glioblastoma. Of these, 75 patients (34.6%) experienced CRS, primarily mild to moderate (Grade 1-2), with severe cases (Grade 3-5) being rare. Management strategies included supportive care, corticosteroids, and tocilizumab for severe CRS. The incidence and severity of CRS in solid tumor trials were lower than in hematologic malignancies. Conclusion: While CRS is a concern in CAR-T therapy for solid tumors, its lower incidence and severity compared to hematologic cancers highlight the need for tailored management strategies. Future research should focus on optimizing patient outcomes and mitigating CRS risks to develop safer and more effective CAR-T therapies for solid tumors.
Author(s):Jasraj Singh Anand1 *, Indermeet Anand2 , Dr. Maheshvari Patel3