Incidence and outcomes of cytomegalovirus reactivation after chimeric antigen receptor T-cell therapy

Abstract

Cytomegalovirus (CMV) reactivation is a major complication among seropositive allogeneic hematopoietic cell transplantation (HCT) recipients; however, data regarding CMV reactivation after chimeric antigen receptor T (CAR T) cell therapy are limited. In this single-center retrospective study, we report the incidence and outcomes of 95 adult CMV seropositive patients who received CAR T cell therapy between February 2018 and February 2023. CMV outcomes were CMV reactivation (any viremia) and clinically significant CMV infection (cs-CMV, viremia requiring antiviral treatment). Thirty-one patients (33%) had evidence of CMV reactivation (any viremia), and 10 patients (11%) had cs-CMV. The median time from CAR T cell infusion to CMV reactivation was 19 days (IQR, 9-31). The cumulative incidence of CMV (any viremia) was significantly higher among patients with grade 3-4 cytokine release syndrome (67 vs. 28%; P=0.01), and those who received corticosteroids (39 vs. 21%; P=0.03), anakinra (56 vs. 28%; P=0.02), or ≥2 immunosuppressants (41 vs. 21%; P=0.02). Receipt of corticosteroids (18 vs. 0%; P=0.004), tocilizumab (14 vs. 0%; P=0.04), anakinra (33 vs. 7%; P=0.008), and ≥2 immunosuppressants (20 vs. 0%; P=0.001) were all associated with cs-CMV. Receiving ≥2 immunosuppressants was associated with a 2-fold increase in CMV reactivation in multivariate analyses (aOR 2.27, 95%CI 1.1-4.8, P=0.03). Overall, 1-year mortality was significantly higher in those with CMV reactivation (57% vs. 23%, P=0.001). Immunosuppression, particularly corticosteroids, for the management of CAR T cell toxicities is a major risk factor for CMV reactivation. CMV preventive strategies in high-risk CAR T recipients might improve outcomes.