Toxicity after chimeric antigen receptor T-cell therapy : Overview and management of early and late onset side effects

Abstract

The transfusion of chimeric antigen receptor (CAR) T‑cells has become established as anew treatment option in oncology; however, this is regularly associated with immune-mediated side effects, which can also run asevere course and necessitate aspecific treatment and intensive medical treatment. A literature review was carried out on CART-cell therapy, toxicities and the management of side effects. The cytokine release syndrome (CRS) and the immune effector cell-associated neurotoxicity syndrome (ICANS) regularly occur shortly after CART-cell treatment. The symptoms of CRS can range from mild flu-like symptoms to multiorgan failure. In addition to mild symptoms, such as disorientation and aphasia, ICANS can also lead to convulsive seizures and brain edema. The management of CRS and ICANS is based on the severity according to the grading of the American Society for Transplantation and Cellular Therapy (ASTCT). Tocilizumab and corticosteroids are recommended for CRS and corticosteroids are used for ICANS. In the further course persisting hypogammaglobulinemia and cytopenia are frequent even months after the initial treatment and promote infections even months after CAR T‑cell therapy. Potentially severe complications regularly occur after CART-cell therapy. An interdisciplinary cooperation between intensive care physicians, hematologists, neurologists and specialists in other disciplines is of decisive importance for the optimal care of patients after CAR T‑cell therapy.