Low-dose chidamide maintenance therapy following allogeneic hematopoietic stem cell transplantation in T-cell acute lymphoblastic leukemia or lymphoma: A phase 2, open-label, multicenter, single-arm trial Free

Introduction: T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphomas (TCL) are highly aggressive hematologic malignancies associated with poor prognoses. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) provides a potential curative opportunity and long-term survival for many patients, 20%–30% remain at risk of relapse following transplantation. Chidamide, a subtype-selective histone deacetylase (HDAC) inhibitor, has demonstrated significant antitumor activity and the ability to enhance immune cell-mediated cytotoxicity against T-cell malignancies in vitro and in mouse models. Clinically, chidamide is widely used to treat various T-cell malignancies. This study was conducted to evaluate the efficacy and safety of chidamide as a post-transplant maintenance therapy in patients with T-ALL/TCL.

Methods: This was a phase II, multicenter, single-arm clinical trial (NCT05991973) evaluating low-dose chidamide as maintenance therapy in patients with T-ALL/TCL after allo-HSCT. The key inclusion criteria were: (1) 14-70 years old; (2) diagnosed with T-ALL or T-cell lymphomas (mainly including peripheral T-cell lymphoma, NK/T-cell lymphoma, T-lymphoblastic lymphoma, etc) according to the 2016 WHO classification; (3) confirmed engraftment and achieved complete remission after allo-HSCT. Chidamide was initiated at 10 mg twice weekly (biw) between days 60 and 100 post-transplant, continued for up to 2 years, and could be escalated to a maximum of 20 mg biw at the physician's discretion. The primary endpoint was 2-year relapse-free survival (RFS). Key secondary endpoints included incidence of aGVHD, chronic GVHD, hematological and non-hematological adverse events, non-relapse mortality (NRM), 2-year cumulative incidence of relapse (CIR), 2-year GVHD-free/relapse-free survival (GRFS), and 2-year overall survival (OS).

Results: Between July 2023, and August 2024, 62 patients were screened post-HSCT. A total of 44 patients were included and received the maintenance. The median age at transplant was 30 years (range, 15–59), and 65.9% were male. Diagnoses included T-ALL (n=27), T-cell lymphoblastic lymphoma (T-LBL, n=13), peripheral T-cell lymphoma (n=3), and EBV-positive TCL (n=1). At the time of transplant, 40 patients were in complete remission (CR), and 4 were no remission (NR). The median duration of chidamide treatment was 21.3 months (range, 1.5–24.2 months).

The data cutoff was 31 July 2025. Four patients experienced relapse (range, 1.1–13.2 months), including 2 with NR at transplant. Relapses included hematologic (n=2) and extramedullary (n=2) events. The 2-year CIR was 9.6% (95%CI, 4.9%–18.8%) for patients with chidamide as maintenance therapy. At last follow-up, 40 patients were alive, while 4 had died. Causes of death were relapse (n=1), severe lung infection or pneumonia (n=2), and lung-involved cGVHD (n=1). The 2 years NRM, RFS, and OS were 8.2% (95%CI, 0%–17.5%), 85.8% (95%CI, 75.8%–97.1%), and 89.4% (95%CI, 79.8%–100%), respectively. Among the 4 relapsed patients, one died from disease progression, one achieved CR with salvage therapy and donor lymphocyte infusion but later died of cGVHD, and the remaining two were in CR at last follow-up after salvage therapy. The 2-year cumulative incidence of cGVHD was 38.5% (95%CI, 21.2%–53.9%) after chidamide treatment.

The majority of allo-HSCT recipients tolerated to low-dose chidamide. During our study, the most common treatment-related adverse events (TRAEs) were hematological toxicities, including neutropenia (9.1%), thrombocytopenia (9.1%), and anemia (6.8%), mostly grade 1 to 2. Other TRAEs involved dermatologic, gastrointestinal, hepatobiliary, renal, and infectious disease. No treatment-related deaths due to chidamide occurred.

Conclusion: Low-dose chidamide maintenance therapy following allo-HSCT demonstrated excellent efficacy and manageable safety in patients with T-ALL/TCL. This treatment strategy could be a suitable option for patients with T-ALL/TCL after allo-HSCT.