Toxicity of Chimeric Antigen Receptor T Cells and its Management.

Abstract

Recently, chimeric antigen receptor (CAR) T cell therapy has transformed the treatment armamentarium of relapsed/refractory B lymphoid malignancies. CAR T cells provide an excellent response rate and potential cure for these patients. However, CAR T cells also possess unique and potentially life-threatening immune-mediated side effects. Among these, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are the two most common complications associated with CAR T cell therapy. While the pathogenesis of CRS involves the activation of complex immune axes, including both cellular networks and inflammatory cytokine milieu, the mechanism of ICANS has not been fully elucidated. Other notable toxicities of CAR T cells include macrophage activation syndrome, cytopenia, and potential organ toxicities. Treatments for these complications typically encompass close observation, multidisciplinary supportive measures, and cytokine-modifying agents such as anti-interleukin-6 antibody and systemic corticosteroids. CAR T therapies can cause immunologic adverse events and management of these toxicities could also instigate a profound immune suppression state that predisposes patients to a variety of infectious complications. Prompt diagnosis and proper management of these complications are crucial to minimize CAR T cell-associated complications and to maximize the outcome of CAR T cell therapy.