Complications after CD19+ CAR T-Cell Therapy

SIMPLE SUMMARY: CD19+ Chimeric antigen receptor (CAR) T-cells are used against CD19+ hematologic malignancies, such as high-grade B-cell lymphoma and acute lymphoblastic leukemia. Since this is a relatively new treatment approach, not all potential side effects are well described, and the underlying pathobiology is often not well defined. Here, we summarize current data on the incidence and the current management of CD19+ CAR T-cell complications. We discuss frequently occurring toxicities and we highlight evidence for the occurrence of rarer side effects affecting different organ systems. In addition, we highlight new findings that shed light on the pathophysiology of CAR T-cell-related complications. ABSTRACT: Clinical trials demonstrated that CD19+ chimeric antigen receptor (CAR) T-cells can be highly effective against a number of malignancies. However, the complete risk profile of CAR T-cells could not be defined in the initial trials. Currently, there is emerging evidence derived from post approval studies in CD19+ CAR T-cells demonstrating both short-term and medium-term effects, which were unknown at the time of regulatory approval. Here, we review the incidence and the current management of CD19+ CAR T-cell complications. We highlight frequently occurring events, such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, cardiotoxicity, pulmonary toxicity, metabolic complications, secondary macrophage-activation syndrome, and prolonged cytopenia. Furthermore, we present evidence supporting the hypothesis that CAR T-cell-mediated toxicities can involve any other organ system and we discuss the potential risk of long-term complications. Finally, we discuss recent pre-clinical and clinical data shedding new light on the pathophysiology of CAR T-cell-related complications.