Approximately 80% of the world’s population have been infected by cytomegalovirus (CMV) based on seroprevalence data, and immunosuppressed CMV-seropositive patients are at increased risk for CMV reactivation. 1 After allogeneic hematopoietic cell transplantation (alloHCT), CMV reactivation occurs in 40-45% of CMV-seropositive recipients and is associated with increased non-relapse mortality. 2, 3 As in alloHCT, lymphodepleting conditioning is given before CAR T-cell (CAR T) therapy; thus, the incidence of CMV reactivation may also be increased after CAR T therapy.

The incidence and clinical significance of CMV reactivation after CAR T therapy is not well described. CMV viremia (n= 14) and end organ disease (pneumonitis [n= 2], enteritis [n= 1], encephalitis [n= 2], and retinitis [n= 1)) have been reported after CAR T therapy. 4-12 Another study reported that ten of 60 (17%) CMV-seropositive and-seronegative patients receiving CAR T therapy developed CMV reactivation based upon a single test performed from day+ 14 to+ 21 after CAR T infusion, 13 none of these patients developed CMV organ disease. Interpretation of these studies with regard to CMV reactivation incidence is limited by the unknown or low frequency of testing. Active monitoring with CMV DNA quantitative polymerase chain reaction (qPCR) testing was not described, and CMV reactivation is less likely to be detected if the frequency of testing is low. Therefore, we retrospectively analyzed the clinical outcomes of 65 consecutive patients treated with autologous CD19 targeted CAR T therapy for non-Hodgkin lymphoma from May 2018 to June 2021 who received at least two CMV DNA qPCR tests (Table 1) to determine the incidence of CMV reactivation and its clinical impact. All patients were treated at a single comprehensive cancer center with a dedicated transplant and cellular therapy unit and transfused with leukocyte-reduced blood products that were considered CMV safe. None of the patients received prophylaxis for CMV infection. Patients received prophylaxis against herpes viruses with acyclovir 400 mg by mouth twice a day (renally dosed as needed). CAR T-related clinical data were prospectively gathered as part of the Transplant and Cellular Therapy Program monitoring plan. American Society for Transplant and Cellular Therapy guidelines were used to define and grade cytokine release syndrome (CRS) and immune effector cell-mediated neurotoxicity syndrome (ICANS). 14 Reactivation was defined as a CMV DNA qPCR result> 400 IU/mL occurring from 4 days before CAR T infusion until the time of death or last follow-up. This CMV DNA qPCR threshold was chosen be-