Infectious complications after CAR T-cell therapy: mechanisms, risk stratification, and prevention

Abstract Chimeric antigen receptor (CAR) T-cell therapy is an established treatment for relapsed or refractory B-cell malignancies. Despite therapeutic success, infectious complications remain a major contributor to non-relapsed morbidity and mortality. The risk of infection reflects a prolonged and multifactorial state of immunosuppression resulting from lymphodepleting chemotherapy, treatment-related cytopenia, sustained CD4 + T-cell lymphopenia, B-cell aplasia with hypogammaglobulinemia, and the use of corticosteroids or cytokine-directed therapies for the management of immune effector cell-associated toxicities (i.e., cytokine-release syndrome and immune effector cell–associated neurotoxicity). The spectrum of infections has evolved over time. Bacterial infections are observed most frequently in the early post-infusion period, whereas viral and opportunistic infections become more prominent later, particularly in patients with delayed immune recovery. Infection risk is also influenced by the underlying malignancy, prior exposure to treatment, and the type of CAR T-cell product used. For example, BCMA-directed CAR T-cell therapy has been associated with a higher infection burden, likely related to profound plasma cell depletion and sustained impairment of humoral immunity. Preventing infections in this setting requires a structured and individualized approach. Common strategies include antiviral and Pneumocystis jirovecii pneumonia prophylaxis, the selective use of antibacterial and antifungal prophylaxis during periods of severe or prolonged cytopenia, immunoglobulin replacement in patients with clinically significant hypogammaglobulinemia, and vaccination schedules guided by immune recovery. Therefore, coordinated and risk-adapted prevention is essential to minimize infectious complications and to improve long-term outcomes after CAR-T cell therapy. This review summarizes the current evidence and major recommendations of international guidelines to provide an updated overview of infection mechanisms, risk stratification, and preventive strategies for patients receiving CAR T-cell therapy.