Predicators and Outcomes of Cytomegalovirus Reactivation in Chimeric Antigen Receptor T-Cell Therapy: A Systematic...

Cytomegalovirus (CMV) reactivation is a common complication in immunocompromised patients, but poorly defined in those undergoing chimeric antigen receptor T-cell (CAR-T) therapy. This systematic review investigates the predictors and outcomes of CMV reactivation in CAR-T recipients, focusing on survival, relapses, and nonrelapse mortality (NRM).

A systematic review was conducted following PRISMA 2020 guidelines to compare outcomes between CMV reactivation (R) and nonreactivation (NR) groups. A comprehensive search of PUBMED, EMBASE, and CENTRAL identified 172 studies, of which 4 met the inclusion criteria. Data was synthesized using descriptive statistical analysis to report frequencies and percentages.

Among 462 CAR-T recipients, 114 (24.7%) experienced CMV reactivation, with a median onset of 20 days and 1.73% developing end-organ disease. Reactivation was more common among those receiving BCMA-targeted CAR-T (7% vs. 2.9%) and with prior allo-HSCT (35% vs. 7%). Severe CRS (11.4% vs. 8.6%) and ICANS (37.7% vs. 26.7%) were also more frequent in the reactivation group. Use of immunosuppressive therapy, including steroids (56% vs. 42.8%) and tocilizumab-anakinra (12% vs. 5%), was higher. Studies showed increased 1-year mortality and relapse in the reactivation group, with CMV reactivation independently predicting mortality (HR 2.3, 95% CI: 1.2-4.5, P = .02).

CMV reactivation is a serious complication in CAR-T therapy, associated with higher mortality, relapse, and NRM. Key risk factors include BCMA-targeted CAR-T, prior allo-HSCT, and severe CRS/ICANS. Targeted monitoring and prophylactic strategies are crucial to improve outcomes.