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Introduction: Chronic graft-versus-host disease (cGVHD) is a fatal late complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Several studied demonstrate that the interaction between T follicular helper (Tfh) cells and B cells promotes pathogenicity of cGVHD. The glucocorticoids are still the first-line standard treatment of cGVHD, which are effective in only 50-60% of cases. Chidamide, is an oral innovative subtype-selective histone deacetylase (HDAC) inhibitor, independently developed in China. It could induce chromatin remodeling, epigenetic changes, inhibiting cell cycle and thereby inducing tumor cell apoptosis. It is primarily approved for the treatment of relapsed or refractory peripheral T-cell lymphoma (R/R-PTCL) and has superior response in Tfh-PTCL. Therefore, we conduct a prospective clinical study (NCT05140616), to investigate the efficacy and safety of chidamide in steroid-dependent and steroid-refractory cGVHD (SR-cGVHD). Methods: Patients who undergoing allo-HSCT with modified myeloablative BU/CY conditioning regimen and developing SR-cGVHD at the First Affiliated Hospital of Soochow University were enrolled. The diagnosis and grade of SR-cGVHD were based on the NIH criteria. All patients received oral chidamide 15mg twice a week and a total of two cycles was recommended. The primary study endpoint was overall response rate (ORR) at 3 months. The secondary endpoints were the safety of chidamide, overall survival (OS), progression-free survival (PFS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) of enrolled patients. Survival outcomes were conducted with the Kaplan-Meier method. Results: 11 enrolled patients included 8 (72.7%) males and 3 (27.3%) females. The median age of patients was 34 years (range 16-50 years). The patients consisted of 4 (36.4%) acute myeloid leukemia, 4 (36.4%) acute lymphoblastic leukemia, 2 (18.2%) myelodysplastic syndrome and 1 (9.1%) lymphoblastic lymphoma. Of 11 patients. 6 (54.5%) were HLA-matched sibling donor transplantation and 5 (45.5%) were haplo-identical donor transplantation. Patients were assessed and divided into moderate group (4, 36.4%) and severe group (7, 63.6%) according to the NIH criteria. By analyzing the targeted organs, there were 9/11 (81.9%) patients with skin involvement. The pulmonary cGVHD occurred in 7 (63.6%) patients and 5 (45.5%) patients had liver-cGVHD. For enrolled patients, the ORR to chidamide therapy was 45.5%, including 1 (9.1%) patient with CR and 4 (36.4%) with PR. In addition, 4 (36.4%) patients were in stable condition during treatment. The median following-up time was 31 months (range 1-41 months) after the initiation of chidamide. The 2-year OS was 81.8%, 2-year PFS was 71.6%, 2-year CIR was 12.5% and 2-year NRM was 18.2%, respectively. 1 (9.1%) patient died due to relapse of leukemia and 2 (18.2%) died due to pulmonary cGVHD progression. The adverse events (AEs) were observed in 3 (27.3%) patients, 1(9.1%) thrombocytopenia, 1 (9.1%) gastrointestinal tract reaction and 1 (9.1%) cough were included. AEs were obviously improved by symptomatic treatment. Conclusion: Collectively, our results primarily suggested selective HDAC inhibitor chidamide could serve as potential therapeutic choice for SR-cGVHD.
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