Chidamide Maintenance Therapy for Patients with Peripheral T-Cell Lymphoma: A Multicenter Real-World Analysis

Background:

Peripheral T-cell lymphoma (PTCL) is characterized by its aggressive nature, lack of a standard treatment regimen, high recurrence rate. Recent studies have shown that consolidation therapy and long-term maintenance therapy after induction chemotherapy could improve the prognosis of patients with PTCL. As a selective oral histone deacetylase inhibitor, chidamide can deacetylate lysine residues to inhibit the transcription of downstream genes, which is used to treat patients with relapsed or refractory PTCL. However, the role of chidamide in PTCL maintenance therapy is still uncertain.

Aims:

This study aimed to assess the efficacy and safety of real-world chidamide monotherapy as maintenance therapy in PTCL.

Methods:

Chidamide was given orally as maintenance therapy after chemotherapy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS) and maintenance treatment adverse events (AEs).

Results:

A total of 69 patients were enrolled between June 2016 and October 2022. The median age was 61 years (range: 17-93 years); 43.5% (30/69) of the patients constituted the middle-high risk group. 60.9% (42/69) of the patients received more than two lines of therapy. Furthermore, 14.5% (10/69) of the patients underwent hematopoietic stem cell transplantation, 91.3% (63/69) of the patients received chidamide at doses of 20-30 mg twice a week as maintenance therapy. In total, 56.5% (39/69) and 43.5% (30/69) of the patients achieved CR and PR, respectively.

The median follow-up time of the 69 patients was 43.4 months (21.7-98.4 months), of which 91.3% (63/69) of the patients were followed up for more than 2 years. By the end of the follow-up, the overall CR rate was 47.8%, and the median OS was not reached, but the median PFS was 54.8 months. Furthermore, 20% (6/30) of the patients with PR converted to CR during the maintenance therapy with chidamide. 37.7% (26/69) of the patients had disease progression. Eleven patients died, and one patient was lost to follow-up. The 2-year OS and PFS rates for all of the patients were 88.2% and 75.3%, respectively.

Patients with CR at baseline had better 2-year PFS than the PR group (87.2% vs. 59.6%, P = 0.0392), and no significant difference in 2-year OS was observed (94.9% vs. 79.3%, P = 0.165). Patients who received chidamide at doses of 20-30 mg twice a week as maintenance therapy had better 2-year PFS and OS than the 15 mg group (79.3% vs. 33.3%, P = 0.0069; 92.1% vs. 40%, P = 0.0002). Patients who received induction therapy combined with chidamide had better 2-year PFS than those who received induction therapy without chidamide (83% vs. 57.7%, P = 0.0202). The presence or absence of hematopoietic stem cell transplantation before maintenance therapy was not associated with the efficacy of chidamide maintenance therapy (2-year PFS = 76.2% vs. 70%, P = 0.1812; 2-year OS = 90% vs. 87.9%, P = 0.7435). Univariate analysis showed that age and remission status at baseline were associated with PFS and that Eastern Cooperative Oncology Group Performance Status（ECOG）, remission status at baseline, and maintenance dose of chidamide were associated with OS. Multivariate analysis showed that age and remission status at baseline were independent prognostic factors for PFS (Hazard Ratio (HR) = 0.302, P = 0.02; HR = 3.524, P = 0.014) and that ECOG and remission status at baseline were independent prognostic factors for OS (HR = 76.932, P = 0.001; HR = 29.400, P = 0.019).

The most common maintenance treatment AE was neutropenia (n = 32, 46.4%), with a grade 3/4 AE rate of 20.3%. The most common non-hematologic AEs were gastrointestinal symptoms (n = 10, 14.5%) and malaise (n = 10, 14.5%), and no grade 3/4 AEs were found. Seventeen of the enrolled patients had dose adjustments due to adverse effects, and no treatment-related deaths were observed during the study period.

Conclusion:

In PTCL patients with CR or PR, maintenance therapy with chidamide monotherapy is effective and well tolerated. Furthermore, disease remission status before maintenance therapy significantly influences the efficacy of maintenance therapy.

No relevant conflicts of interest to declare.