Incidence and Outcomes of Cytomegalovirus Reactivation after Chimeric Antigen Receptor T Cell Therapy

Introduction Cytomegalovirus (CMV) reactivation is a major complication among seropositive allogeneic hematopoietic cell transplantation (HCT) recipients; however, the incidence and outcomes of CMV reactivation in patients undergoing chimeric antigen receptor T (CAR T) cell therapy remain poorly understood. Objective Discuss the incidence and outcomes of CMV reactivation in patients treated with CAR T cell therapy Methods Single-center retrospective study 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-CMVi, viremia requiring antiviral treatment). Results Of the 148 patients who received CAR T cell therapy during this period, 95 patients met the inclusion criteria. Patients who were CMV seronegative, had history of previous allogeneic HCT, received letermovir prophylaxis, or had missing CMV data were excluded. Among patients who developed cytokine release syndrome (CRS), 66 (89%) received tocilizumab with median number of 8mg/kg doses of 2.5 (IQR, 1 to 4); 52 (70%) received dexamethasone with median dose of 108 mg (IQR, 51 to 160), and 9 (12%) received anakinra. 31 patients (33%) had evidence of CMV reactivation (any viremia) and 10 patients (11%) had cs-CMVi. The median time from CAR T cell infusion to CMV reactivation was 19 days (IQR, 9 to 31). Among those with clinically significant CMV reactivation, the median peak viremia was 2388 IU/mL. Among those who did not reactivate, 31 patients (48%) received dexamethasone, at a median dose of 100 mg (IQR, 30 to 150), whereas in the 10 patients with cs-CMVi, 100% received dexamethasone (P=0.002) with a median dose of 130 mg (IQR, 74 to 263). The cumulative incidence of CMV (any viremia) was significantly higher among patients with grade 3-4 CRS (67 vs 29%; P=0.01), those who received steroids (40 vs 19%; P=0.01) or ≥2 immunosuppressants (43 vs 19%; P=0.01. Fig 1). Receipt of steroids (19 vs 0%; P=0.003), tocilizumab (15 vs 0%; P=0.03) and ≥ 2 immunosuppressants (21 vs 0%; P=0.001) were all associated with risk of cs-CMVi (Fig 1). Receiving ≥2 immunosuppressants was associated with 2.5-fold increase in risk of CMV reactivation in multivariate analyses (aOR 2.54, 95%CI 1.0-6.5, P=0.04). Conclusions CMV reactivation is a common complication of CAR T cell therapy in CMV seropositive individuals. Although confirmatory studies are needed, our data shows that immunosuppression, in particular steroids, for management of CAR T cell toxicities is a major risk factor for CMV reactivation, and close monitoring might be indicated in this setting.