A prospective phase 2 study of combination epigenetic therapy against relapsed/refractory peripheral T cell lymphoma.

in Med (New York, N.Y.) by Kaiyang Ding, Hailing Liu, Haiyan Yang, Huayuan Zhu, Jie Ma, Hongling Peng, Hongming Huang, Wei Shi, Lei Cao, Wei Wu, Xiaoli Zhao, Xiao Shi, Jianyong Li, Xiaohui Zhang, Lei Fan

TLDR

  • This study tested a new treatment for a type of cancer called peripheral T cell lymphoma (PTCL). The treatment involved a combination of two drugs, azacitidine and chidamide, with another drug called gemcitabine and oxaliplatin (GemOx). The study found that the combination of these drugs was effective in treating PTCLs, especially in patients with a specific type of PTCL called angioimmunoblastic T cell lymphoma (AITL). The study was funded by the Natural Science Foundation of Jiangsu Province (BK20232039).

Abstract

Peripheral T cell lymphomas (PTCLs) are prototypical epigenetic malignancies with invariably poor prognoses. Novel and effective therapeutic strategies are needed to improve clinical outcomes, particularly in relapsed/refractory patients. We conducted a multicenter phase 2 study to evaluate the therapeutic efficacy of azacitidine and chidamide, alone or in combination with gemcitabine and oxaliplatin (GemOx), in patients with relapsed/refractory PTCLs (registration number: ChiCTR2000037232). The primary endpoint was the best overall response rate. As of May 1st, 2024, thirty patients were evaluable for efficacy and toxicity. The best overall response rate was 53.3%, meeting its primary endpoint. Among the patients with angioimmunoblastic T cell lymphoma (AITL; N = 19), a numerically higher response rate was observed, regardless of whether chemotherapy was combined, compared to patients with non-AITL. After a median follow-up of 36.6 months, median progression-free survival and overall survival were 7.1 and 8.7 months, respectively. Patients with AITL who received combination chemotherapy (N = 12) achieved the most promising response rates (overall response rate, 91.7%; complete remission rate, 66.7%) and survival outcomes (median progression-free survival, 17.2 months; median overall survival, 38.8 months). The most common grade 3-4 toxicities were neutropenia (40.0%) and thrombocytopenia (30.0%). The combination of epigenetic therapy with GemOx was well tolerated and highly effective in patients with relapsed/refractory PTCLs. Patients with AITL, in particular, may benefit more from this combination treatment and should be the focus of future studies. This work was funded by the Natural Science Foundation of Jiangsu Province (BK20232039).

Overview

  • The study aims to evaluate the therapeutic efficacy of azacitidine and chidamide, alone or in combination with gemcitabine and oxaliplatin (GemOx), in patients with relapsed/refractory peripheral T cell lymphomas (PTCLs).
  • The primary endpoint was the best overall response rate. The study included 30 evaluable patients, with 53.3% achieving a best overall response. The best response rate was observed in patients with angioimmunoblastic T cell lymphoma (AITL).
  • The study aimed to improve clinical outcomes, particularly in relapsed/refractory patients. The results suggest that the combination of epigenetic therapy with GemOx is well tolerated and highly effective in patients with PTCLs, with patients with AITL benefiting the most.

Comparative Analysis & Findings

  • The study compared the outcomes observed under different experimental conditions or interventions, specifically the combination of azacitidine and chidamide with GemOx versus azacitidine and chidamide alone or GemOx alone. The results showed a numerically higher response rate in patients with AITL, regardless of whether chemotherapy was combined, compared to patients with non-AITL. The combination of epigenetic therapy with GemOx was well tolerated and highly effective in patients with PTCLs, with patients with AITL benefiting the most.

Implications and Future Directions

  • The study's findings suggest that the combination of epigenetic therapy with GemOx is well tolerated and highly effective in patients with PTCLs, with patients with AITL benefiting the most. Future studies should focus on patients with AITL and explore the potential of this combination treatment in other types of PTCLs. The study was funded by the Natural Science Foundation of Jiangsu Province (BK20232039).
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