Tucidinostat Maintenance after Achieving Objective Response to First-Line Therapy in Peripheral T-Cell Lymphoma: A Single-Center Retrospective Case-Control Study

Background Peripheral T-cell lymphoma (PTCL) is a highly heterogenous hematological malignancy with poor outcome and prognosis, many patients experience recurrence. Histone deacetylase inhibitors (HDACis) have been proven to improve the prognosis of patients with relapsed/refractory (R/R) PTCL. Tucidinostat is a novel HDACi approved for treating R/R PTCL, however，clinical data is needed to determine the effectiveness of tucidinostat maintenance therapy in PTCL.

Objective To retrospectively evaluate the efficacy and safety of tucidinostat maintenance in PTCL patients who achieved objective response after first-line therapy.

Methods This is a retrospective, single-center, case-control study. We reviewed 473 newly diagnosed PTCL patients in the First Affiliated Hospital, Zhejiang University School of Medicine(Zhejiang, China) from January 2014 to December 2021. After excluding patients with insufficient clinical data, other concurrent tumor, natural killer/T-cell lymphoma, mycosis fungoides, or sequential transplantation, there were 32 PTCL patients who achieved objective response after first-line therapy received tucidinostat maintenance therapy. Patients who achieved objective response without maintenance therapy served as a candidate control pool. The two groups of patients were subjected to 1:1 propensity score matching (matching tolerance = 0.02), according to whether the international prognostic index (IPI) was ≥3, pathological subtype, whether the given patient was older than 65 years, and gender; 25 pairs (n = 50) were matched. The primary endpoints of this study were progress-free survival (PFS), overall survival (OS), and adverse events (AEs). The baseline clinical characteristics were compared using t-test for continuous variables, and chi-square or Fisher's exact test for categorical variables. Survival outcomes were assessed with Kaplan-Meier method. P < 0.05 was considered significant. The SPSS v25.0 software was used for statistical analysis.

Results Among the patients in the tucidinostat maintenance (n = 25) and control (n = 25) groups, the median ages were 64 (30-90) and 63 (18-79) years old, respectively; the male ratios were 64.0% (16/25) and 68.0% (17/25), respectively; the proportions of patients ≥65 years were 44.0% (11/25) and 40.0% (10/25), respectively; the proportions of patients with IPI ≥3 were 52.0% (13/25) and 44.0% (11/25), respectively; and the proportions of patients with PIT ≥2 were 48.0% (12/25) and 44.0% (11/25), respectively (all P >0.05), suggesting a balanced distribution of baseline clinical characteristics in the 2 groups (Table 1). The complete response rates of the case and control groups were 72.0% (18/25) and 56.0% (14/25), respectively (P >0.05); the median duration of follow-up was 27.4 (6.7-96.0) and 22.2 (4.3-99.6) months, respectively; the median PFS was 54.0 and 12.3 months, respectively; the 2-year PFS was 67.9% and 25.3%, respectively (P < 0.01, Figure 1A); the median OS was unreached and 37.3 months, respectively; and the 2-year survival rate was 100% and 54.6%, respectively (P < 0.01, Figure 1B). No significant differences in PFS were observed between the 25 patients after matching and all of the 32 patients on tucidinostat maintenance (P = 0.878), indicating that there was no significant selection bias and the case group could represent the overall population.

The total sample of 32 patients received 20 or 30 mg tucidinostat (both P.O., twice weekly) according to their physical status, age, and tolerance. Among them, 59.4% (19/32) took 20 mg (2 cases had dose reduction to 10-15 mg due to AEs) and 40.6% (13/32) took 30 mg (2 cases had dose reduction to 20 mg due to AEs), with median duration of 12.9 (2.4-86.4) months. The most common grade 3-4 AEs were neutropenia (28.1%), thrombocytopenia (15.6%), and anemia (12.5%), which mostly occurred within 6 weeks of initial administration and were relieved after symptomatic treatment .

Conclusion Our retrospective case-control data preliminarily shows that tucidinostat maintenance is effective and has manageable safety for PTCL patients who acheived objective responses after first-line therapy, and increases their PFS and OS. However, a larger-sample, prospective, multicenter cohort study is needed to further determine the optimal dosage of tucidinostat maintenance and verify its therapeutic efficacy and safety.

No relevant conflicts of interest to declare.