Cytomegalovirus (CMV) Reactivation within in the First Year after Chimeric Antigen Receptor (CAR) T Cell Therapy: Experience from the First Two Years at a Major Cancer Center

Background: Chimeric antigen receptor (CAR) T cell therapy has changed the landscape for the treatment of lymphoma patients with refractory or relapsed disease. Infections due to CAR T have been described during the immediate post-treatment phase, but this is often limited to bacterial infections. Cytomegalovirus (CMV) is rarely described as a complication after CAR T cell therapy, and little is known about the risk factors for reactivation. Our study aimed to identify risk factors for clinically significant CMV infection (CS-CMVi) in CAR T cell recipients one year after therapy.

Methods: Between January 2018 and February 2021, we reviewed 230 patients who received CAR T cell infusions at our center and collected data on demographics, oncological history, characteristics of the CAR T cell therapy, and infectious complications after treatment. Additionally, we collected data on CS-CMVi within one year after CAR T cell therapy. CS-CMVi was defined as CMV requiring treatment due to elevated viral load or development of end-organ disease. Univariate analysis compared patients with and without viral infections; Fischer exact test and Wilcoxon rank sum were used for categorical and continuous variables, respectively.

Results:

Amongst 230 patients, the majority of patients were male (69%), white (65%), had an Eastern Cooperative Oncology Group (ECOG) performance score of 0-1 (82%), underwent CAR T cell therapy for diffuse large B cell lymphoma (DLBCL) (70%) and received axicabtagene ciloleucel (Yescarta) (89%) (Table 1). We identified 24 (10%) of patients who developed CS-CMVi. Patients with CS-CMVi were more likely to be female, have a lower absolute neutrophil and monocyte count 30 days after CAR T therapy, developed grade 2 or higher cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS), required treatment for CRS/ICANS, and had a higher cumulative steroid dose during the first 30 days after CAR T cell infusion (Table 1 and 2). Patients with CS-CMVi had a higher overall mortality rate after 1 year post CAR T when compared to non-infected patients. Patients with CS-CMVi were identified 17 days (range of 0-343) after CAR T cell therapy (Table 3). CAR T cell patients with CS-CMVi had a high rate of end-organ infection with 33% of patients diagnosed with CMV pneumonitis and a 60-day overall mortality rate of 55% after developing CS-CMVi (Table 3).

Conclusion:

CS-CMVi is an under-recognized complication after CAR T cell therapy. Therefore, strategies to prevent the development of end-organ disease and prophylaxis would benefit CAR T cell recipients at high risk for CMV reactivation.