Chidamide As Maintenance in Peripheral T-Cell Lymphoma for Patients in Response after Induction Therapy: A Single Center Retrospective Study
Authors: Zhu Yanan , Wei Juying , Yang Chunmei , Xie Wanzhuo , Tong Yanhong , Yu Wen-Juan , Jin Jie 
Published: December 2023

Background
Peripheral T-cell lymphoma (PTCL) is a set of heterogeneous mature T- and natural killer cell neoplasms, most of which are associated with poor prognosis. PTCL patients usually experience frequent relapses. To improve the poor clinical outcomes of PTCL, novel agents that target various pathways have been studied and developed. Histone deacetylase (HDAC) inhibitors are among the most significant improvements made in recent years. Chidamide, a novel benzamide class of HDAC inhibitor, showed significant efficacy in relapsed/refractory PTCL patients in previous studies. But the role chidamide of as a maintenance therapy in PTCL patients after first-line therapy is still unknown.
Methods
In this retrospective, single-center, single-arm study, a total of 342 newly diagnosed PTCL patients were reviewed in the First Affiliated Hospital, Zhejiang University School of Medicine (Zhejiang, China) from August 2014 to May 2022. Patients with natural killer/T-cell lymphoma, mycosis fungoides were not enrolled. After excluding patients with insufficient clinical data, with other concurrent tumor, received other anti-tumor agents during maintenance therapy, or underwent sequential transplantation, there were 35 PTCL patients achieved objective response after first-line therapy, and received chidamide as maintenance therapy. The primary endpoint of this study was progress-free survival (PFS), overall survival (OS), and adverse events (AEs). Response and progression data were evaluated according to the 2016 Lugano Classification lymphoma response criteria. Adverse events were evaluated according to the National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) version 4.0. Survival outcomes were assessed with Kaplan-Meier method.
Results
35 PTCL patients were enrolled, including angioimmunoblastic T-cell lymphoma (AITL) (13, 37.1%), anaplastic large-cell lymphoma (ALCL) (2, 5.7%), PTCL-NOS (20, 57.1%). There were 22 (62.9%) males and 13 (37.1%) females, 16 (45.7%) patients were over 65 years old, 32 patients (91.4%) had clinical stage III-IV, 9 patients (25.7%) had B symptoms, 8 patients (22.9%) had ECOG score ≥2, 15 patients (42.9%) with IPI score ≥3-5, 18 (51.4%) achieved complete remission (CR) and 17 (48.6%) achieved partial remission (PR) after induction chemotherapy. The median follow-up time was 35.2 months (range 13.0 to 107.7). The median duration of chidamide maintenance therapy was 17.7 months (range 2.4 to 98.0). 22 (62.9%) patients received 20mg chidamide twice a week and 13 (37.1%) used 30mg twice a week . The median PFS and median OS were not reached. The 3-year PFS and OS were 64.9% and 89.2%. Patients who achieved CR after induction chemotherapy had a better prognosis trend. Among the 18 patients who received maintenance therapy after CR, there was no death and the 3-year PFS was 76.4%. Patients with B symptoms had a worse prognosis (P&lt;0.05), the median PFS was 22.5 months, the median OS was not reached, and the 3-year overall survival rate was 75%. The 3-year PFS and OS of the remaining 26 patients without B symptoms were 78.5% and 94.1%, respectively.
The most common grade 3-4 AEs were hematological toxicities, including neutropenia(20.0%), anemia(8.6%), thrombocytopenia(5.7%), mainly in 30mg group, as detailed in Table 1. Adverse events usually occurred during the first 6 weeks, most of with were manageable by supportive care and dose modification, none of the adverse reactions leaded to death. There was no statistical difference in PFS and OS between the 30mg and 20mg groups under current sample size.
Conclusions
Chidamide maintenance is effective and may prolong the PFS and OS for PTCL patients with manageable safety profile. It is an appropriate therapeutic option as up-front consolidation therapy for PTCL patients with complete or partial response after first-line therapy. Larger-sample, prospective, multicenter cohort study is still needed to further confirm the conclusion.