Over the past few years, immune checkpoint inhibitors that can reverse tumor-induced T-cell suppression mediated by inhibitory ligands have produced impressive clinical responses in a broad spectrum of cancers, including several hematologic malignancies. Similarly, T cells genetically modified with chimeric antigen receptors (CARs) to confer specificity for surface antigens such as CD19 have produced extremely high response rates in acute lymphocytic leukemia and have also shown promising activity in B-cell lymphomas and chronic lymphocytic leukemia. However, both of these promising immunomodulatory strategies have toxicities. Checkpoint inhibition may cause autoimmune toxicities such as pneumonitis, pancreatitis, and colitis, while cytokine release syndrome (CRS), neurologic toxicities, and hypersensitivity reactions to CAR constructs have all been observed after CAR T-cell infusions.
Dr. Daniel Lee will discuss identification grading and management of toxicities occurring in patients receiving T cells genetically modified to express CARs.
Dr. Suzanne Topalian will discuss immune-related side effects of checkpoint inhibitors and outline how management can be guided by an understanding of the mechanisms.