Infectious complications of chimeric antigen receptor (CAR) T-cell therapies

CAR T-cells have revolutionized the treatment of many hematological malignancies. Thousands of patients with lymphoma, acute lymphoblastic leukemia, and multiple myeloma have received this “living medicine” and achieved durable remissions. Their place in therapy continues to evolve, and there is ongoing development of new generation CAR constructs, CAR T-cells against solid tumors and CAR T-cells against chronic infections like human immunodeficiency virus and hepatitis B. A significant fraction of CAR T-cell recipients, unfortunately, develop infections. This is in part due to factors intrinsic to the patient, but also to the treatment, which requires lymphodepletion (LD), causes neutropenia and hypogammaglobulinemia and necessarily increases the state of immunosuppression of the patient. The goal of this review is to present the infectious complications of CAR T-cell therapy, explain their temporal course and risk factors, and provide recommendations for their prevention, diagnosis, and management.