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

IntroductionCytomegalovirus (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.MethodsWe 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 × 105 cells/kg) upon detection of >1 × 103 copies/mL CMV DNA in two consecutive tests or >1 × 104 copies/mL once.

A second infusion was administered when TCR-T cell expansion remained undetectable within 7 days, and CMV load remained above 1 × 103 copies/mL. Salvage therapy was initiated when complete remission (CR) was not achieved after 3 weeks.

The primary endpoint was the 4-week CR rate. TCR-T cells were derived from healthy donors.ResultsAmong 25 patients enrolled, 13 developed CMV reactivation and received TCR-T cell therapy.