Infections and CAR-T cells for the treatment of lymphoid malignancies: a narrative review

The use of chimeric antigen receptor-T (CAR-T) cells have revolutionized the therapeutic paradigm of patients with lymphoid malignancies. However, infectious complications represent a frequent CAR-T cell-related adverse event, potentially being a major hurdle for the successful outcome of the patients. The infection incidence follows a biphasic pattern, with "early" infections rising during the first 30 days after CAR-T cells infusion, and "late" infections from day 30 onward. Overall, bacterial infections prevail in the early phase after therapy, with a switch to viral or opportunistic infections in the long-term period, while invasive fungal infections are rare events after CAR-T therapy. Risk factors associated with infectious complications include host-related factors such as the underlying malignancy and previous treatments, and treatment-related factors [CAR-T cell product, cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), immune effector cell-associated hematotoxicity (ICAHT), hypogammaglobulinemia]. Careful attention to signs and symptoms of infections is mandatory for an optimal management of patients undergoing CAR-T therapy, and strategies to mitigate infectious risk are clinically relevant: indeed, over half of non-relapse mortality in these patients is attributed to infections. In the present review we attempt to summarize the current knowledge on infectious complications occurring in patients receiving CAR-T cell therapy for lymphoid malignancies in order to provide the readers tools for better management and prevention strategies.