High Incidence of Cytomegalovirus (CMV) Reactivation in Patients Receiving CAR T-Cell Therapy.

Background Infections are a significant source of non-relapse morbidity following chimeric antigen receptor (CAR) T-cell therapy, but data regarding opportunistic pathogens, including cytomegalovirus (CMV), are scarce. We aimed to identify the incidence and risk factors for CMV infection (CMVI) after CAR T-cells using standardized peri-treatment surveillance testing. Methods We retrospectively analyzed all patients who received CAR T at City of Hope between 12/2017-9/2022. We collated data for all serologic and molecular CMV testing obtained prior to lymphodepletion (LD) and at any time post-infusion, respectively. CMVI was defined as plasma CMV viremia >250 copies/mL. Clinically significant CMV infection (CSCI) was defined as CMVI requiring treatment due to persistently elevated viral load > 500 copies/ml or development of end-organ disease. Characteristics in patients with and without CMVI were compared using the Fischer exact test. A competing risk model was used to estimate the prevalence of CMVI and CSCI, with relapse, subsequent disease-directed therapies, and death serving as competing events. Results 204 patients met the inclusion criteria. Most were male (64.2%); had an Eastern Cooperative Oncology Group performance score of 0-1 (80.9%); underwent CAR T cell therapy for large B cell lymphoma (71.1%) and received axicabtagene ciloleucel (63.7%) (Table 1). We identified 29 (14.2%) patients who developed CMVI post-CAR T before relapse or subsequent therapy; 24 (11.8%) were CSCI. Patients with CMVI were more likely to have positive CMV IgG prior to LD (P=0.03), relapsed disease at apheresis rather than primary refractory disease (P <0.01), and a higher steroid dose intensity for the treatment of CAR T-related toxicity (P=0.03) (Table 1). The 1-year mortality for patients with CSCI vs no CMV infection, 45.8% vs 30.9% (P=0.17). The cumulative incidence of CMVI and CSCI are described in Figure 1. The median onset and duration of CMV viremia were 23 days (range, 1-647) and 23 days (range, 1-758), respectively, and the median peak viral load for those with quantifiable CMV burden was 3452 copies/mL (range, 49-2299459). Seventeen patients (8.3%) had CTCAE grade ≥3 CMV infection and 23 patients received inpatient treatment (11.3%), and 6 patients (2.9%) were admitted to the ICU. The cumulative incidence of end organ disease at 1-year was 2.0%. Two patients (1.0%) developed pneumonitis, 2 patients (1.0%) developed retinitis, and 1 patient (0.5%) developed meningoencephalitis. Based on these findings, we have incorporated CMV IgG testing and surveillance by PCR as an early intervention prior to LD at our center. Conclusion CMVI is an under-recognized complication following CAR T cell therapy. Strategies to manage CSCI and prevent the development of end-organ disease would benefit CAR T cell recipients at high risk for this complication and should be studied in prospective trials.