CMV-specific T-cell receptor-engineered T-cell therapy as first-line treatment for CMV reactivation after haploidentical hematopoietic stem cell transplantation: a phase 2 trial.

Introduction: Cytomegalovirus (CMV) reactivation is a major cause of mortality following haploidentical hematopoietic stem cell transplantation (haplo-HSCT). The application of conventional therapies is limited by hematologic and renal toxicities (ganciclovir and foscarnet) or time-consuming preparation (CMV-specific cytotoxic T lymphocytes [CTLs]). We previously demonstrated the efficacy and safety of CMV-specific T-cell receptor-engineered T (TCR-T) cells for treating CMV reactivation post-haplo-HSCT. Methods: We conducted a phase 2 trial using the previously established highest dose to evaluate efficacy and safety as first-line therapy in a larger cohort. Patients received CMV TCR-T cell infusions (5 × 10 Results: Among 25 patients enrolled, 13 developed CMV reactivation and received TCR-T cell therapy. Twelve (12/13, 92.3%, 95% CI: 66.7%-98.6%) achieved CR by week 4. Eleven (11/12, 91.7%, 95% CI: 64.6%-98.5%) maintained CR without further antiviral therapy, with median follow-up of 1011 (range: 657-1561) days post-infusion. Two cases of grade 1 cytokine release syndrome (CRS) occurred. TCR copy number increased ≥10 Discussion: These findings highlight the long-term efficacy and safety of TCR-T cells as first-line therapy for CMV reactivation post-haplo-HSCT. Trial Registration: www.clinicaltrials.gov, identifier NCT05140187.