Cytomegalovirus reactivation in patients with large B-cell lymphoma treated with chimeric antigen receptor T-cell therapy

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has improved outcomes of relapsed and/or refractory large B-cell lymphoma (r/r LBCL). However, its off-tumor effects result in severe prolonged humoral immune deficiency. Cytomegalovirus (CMV) is a latent virus that can be life-threatening in immunosuppressed patients. In the setting of CAR T-cell therapy, Asian race is a risk factor for clinically significant CMV infection. However, the effect of CAR T-cell therapy on CMV reactivation in Japanese patients remains unclear. Previous reports used polymerase chain reaction (PCR), but we used the pp65 antigenemia assay to retrospectively investigate long-term effects in patients with r/r LBCL. The study included 46 patients. Nine (19.6%) developed CMV reactivation, with a median onset of 13 days. Six of these patients received preemptive therapy, and none developed CMV end-organ disease. Primary refractory disease, grade 2-4 cytokine release syndrome, and high-dose corticosteroids were risk factors for CMV reactivation. Long-term follow-up showed that CMV reactivation rarely occurred later than 28 days post-infusion. Our study using the pp65 antigenemia assay showed a similar incidence of CMV reactivation, onset, and risk factors to those in the previous reports using PCR.

Keywords: CAR T-cell therapy; Cytomegalovirus reactivation; Hypogammaglobulinemia; Large B-cell lymphoma.