Low-dose chidamide maintenance therapy following allogeneic hematopoietic cell transplantation in T-cell acute lymphoblastic leukemia or lymphomas: a phase II, open-label, multicenter, single-arm trial.

Abstract

Despite allogeneic hematopoietic cell transplantation (allo-HCT), relapse remains a leading cause of treatment failure for patients with T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphomas (TCL). Given the immunomodulatory properties of histone deacetylase inhibitors, this phase II trial (NCT05991973) investigated chidamide maintenance to reduce post-transplant relapse risk for T-ALL/TCL. In this multicenter, open-label study, patients aged 14-70 years in remission after first allo-HCT received oral chidamide (10 mg twice weekly) for up to 96 weeks. The primary endpoint was 2-year relapse-free survival (RFS). Secondary endpoints included overall survival (OS), cumulative incidence of relapse (CIR), non-relapse mortality (NRM), chronic GVHD, and safety. Outcomes were also compared post hoc with a matched control cohort without maintenance therapy. Between July 2023 and August 2024, 44 patients were enrolled. At a median follow-up of 24.3 months (IQR 18.2-25.7), the 2-year RFS was 83.7% (95% CI 73.3%-95.6%). Secondary endpoints showed a 2-year OS of 89.6% (80.3%-100%), CIR of 11.8% (1.9%-21.7%), NRM of 4.5% (0%-10.7%), and chronic GVHD of 38.3% (23.0%-53.5%). Treatment-emergent adverse events were predominantly grade 1-2 and manageable. The most frequent events were leukopenia (5 [11%]), thrombocytopenia (5 [11%]) and nausea or vomiting (5 [11%]). Chidamide as maintenance could be a potential prophylactic strategy of relapse after allo-HCT for T-ALL/TCL, warranting further confirmation through phase III trials. National Key Research and Development Program of China; National Natural Science Foundation of China; Zhejiang Provincial Natural Science Foundation of China.