Predictors and clinical outcomes of CMV reactivation in CAR-T therapy: A systematic review.

Abstract

2543 Background: Cytomegalovirus (CMV) reactivation is a common complication in immunocompromised patients, particularly those undergoing chimeric antigen receptor T-cell (CAR-T) therapy. CMV reactivation has been linked to increased morbidity and mortality due to immune dysregulation, relapses, and treatment-related toxicity. This systematic review investigates the predictors and outcomes of CMV reactivation in CAR-T recipients, focusing on survival, relapses, and non-relapse mortality (NRM). Methods: A systematic review was conducted following PRISMA guidelines to compare characteristics and outcomes between CMV reactivation (R) and non-reactivation (NR) groups. A comprehensive search of PUBMED, EMBASE, and CENTRAL identified 172 studies, of which only four met the inclusion criteria after screening. A descriptive statistical analysis was performed to calculate frequencies and percentages. Results: Among 462 patients with CAR-T therapy, 114 (24.7%) experienced CMV reactivation. The median time from CAR-T therapy to CMV reactivation was 20 days (Range: -1 to 73), with an incidence of CMV disease with end-organ damage at 1.73%. Most patients received axicabtagene ciloleucel (71%) and had lymphoma (88%). Our analysis identified a higher proportion of patients receiving BCMA-targeted CAR-T therapy (7% vs. 2.9% in NR) and a greater prevalence of prior allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the R group (35% vs. 7% in NR). Severe CRS (Grade ≥3) was more common in the R group (11.4% vs. 8.6%), as was severe ICANS of ≥3 (37.7% vs. 26.7%). Immunosuppressive therapy use, including steroids (56% vs. 42.8%) and combination therapy with tocilizumab and anakinra (12% vs. 5%), was significantly higher in the R group. Outcomes varied across studies, with Lin et al. and Khawaja et al. reporting higher one-year mortality in R vs. NR groups (57% vs. 23%, P = .001; 53% vs. 38%). Khawaja et al. also noted higher NRM (48% vs. 33%). Chen et al. identified CMV reactivation (HR 2.3, 95% CI: 1.2–4.5, P = .02) as an independent mortality predictor, with relapse rates of 71.4% in R and 41.2% in NR. Conclusions: CMV reactivation is a significant complication in CAR-T therapy, linked to worse outcomes, including increased mortality, relapse, and NRM. Predictors include BCMA-targeted CAR-T therapy, prior allogeneic HSCT, severe CRS/ICANS, and associated treatments. Targeted CMV monitoring, prophylaxis, and immunosuppressive strategies are essential for mitigating reactivation risks and improving outcomes in CAR-T recipients.