Interleukin Inhibitors in Cytokine Release Syndrome and Neurotoxicity Secondary to CAR-T Therapy

Abstract

Introduction: Chimeric antigen receptor T-cell (CAR-T) therapy is an innovative therapeutic option for addressing certain recurrent or refractory hematological malignancies. However, CAR-T cells also cause the release of pro-inflammatory cytokines that lead to life-threatening cytokine release syndrome and neurotoxicity. Objective: To study the efficacy of interleukin inhibitors in addressing cytokine release syndrome (CRS) and neurotoxicity secondary to CAR-T therapy. Methodology: The authors conducted a bibliographic review in which 10 articles were analyzed. These included cut-off studies, case reports, and clinical trials involving 11 cancer centers and up to 475 patients over 18 years of age. Results: Tocilizumab is the only interleukin inhibitor approved to address CRS secondary to CAR-T therapy due to its efficacy and safety. Other inhibitors, such as siltuximab and anakinra, could be useful in combination with tocilizumab for preventing severe cytokine release and neurotoxicity. In addition, the new specific inhibitors could be effective in mitigating CRS without affecting the cytotoxic efficacy of CAR-T therapy. Conclusion: More lines of research should be opened to elucidate the true implications of these drugs in treating the side effects of CAR-T therapy.

Keywords

• CAR-T cells
• cytokine release syndrome
• neurotoxicity
• interleukin inhibitors