Cytomegaloviral Infections in Recipients of Chimeric Antigen Receptor T-Cell Therapy: An Observational Study With Focus on Oncologic Outcomes

Abstract

Abstract Background Patients with B-cell lymphoma and acute lymphoblastic leukemia (ALL) who receive chimeric antigen receptor T-cell (CAR-T) therapy may experience clinically significant cytomegalovirus infection (CS-CMVi). However, risk factors for CS-CMVi are not well defined. The aims of our study were to identify risk factors for CS-CMVi and the association between CS-CMVi and nonrelapse mortality (NRM) in lymphoma and ALL patients after CAR-T therapy. Methods We performed a retrospective single-center cohort analysis of CAR-T recipients between January 2018 and February 2021 for treatment of lymphoma and ALL. We collected data on demographics, oncologic history, CAR-T therapy–related complications, and infectious complications within 1 year of therapy. Results Of 230 patients identified, 22 (10%) had CS-CMVi. At 1 year following CAR-T therapy, 75 patients (33%) developed relapsed disease and 95 (41%) died; NRM at 1 year was 37%. On Cox regression analysis, Asian or Middle Eastern race (adjusted hazard ratio [aHR], 13.71 [95% confidence interval {CI}, 5.41–34.74]), treatment of cytokine release syndrome/immune effector cell–associated neurotoxicity syndrome with steroids (aHR, 6.25 [95% CI, 1.82–21.47]), lactate dehydrogenase at time of CAR-T therapy (aHR, 1.09 [95% CI, 1.02–1.16]), and CMV surveillance (aHR, 6.91 [95% CI, 2.77–17.25]) were independently associated with CS-CMVi. CS-CMVi was independently associated with NRM at 1 year after CAR-T therapy (odds ratio, 2.49 [95% CI, 1.29–4.82]). Conclusions Further studies of immunologic correlatives and clinical trials to determine the efficacy of prophylactic strategies are needed to understand the role of CS-CMVi and post–CAR-T mortality.