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.

Iyer:Salarius Pharmaceuticals, Inc.: Consultancy. Ahmed:Merck: Research Funding; Chimagen: Consultancy, Research Funding; Servier: Membership on an entity's Board of Directors or advisory committees; Tessa Therapeutics: Consultancy, Research Funding; Myeloid Therapeutics: Consultancy; Xencor: Research Funding; Seagen: Research Funding. Nieto:Secura Bio: Research Funding; Affimed: Other: Scientific advisory Board, Research Funding; Astra Zeneca: Research Funding. Ariza-Heredia:Oxford Immunotec: Research Funding; Merck: Research Funding. Chemaly:NCI/NIH: Research Funding; AiCuris: Research Funding; Ansun Biopharma: Other: Personnel fees, Research Funding; Genentech: Other: Personnel fees, Research Funding; Chimerix: Research Funding; Janssen: Other: Personnel fees, Research Funding; Karius: Research Funding; MERCK: Other: Personal fees, Research Funding; Oxford Immunotec: Other: Personal fees, Research Funding; Takeda/Shire: Other: Personnel fees, Research Funding; Viracor: Research Funding; Qiagen: Other: Personnel fees; Partner Therapeutics: Other: Personnel fees; Pulmotec: Other: Personnel fees; Shinogi: Other: Personnel fees; Adagio: Other: Personnel fees.