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

IF 12.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Med Pub Date : 2024-07-25 DOI:10.1016/j.medj.2024.07.007
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
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引用次数: 0

Abstract

Background: 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.

Methods: 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.

Findings: 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%).

Conclusions: 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.

Funding: This work was funded by the Natural Science Foundation of Jiangsu Province (BK20232039).

针对复发/难治性外周 T 细胞淋巴瘤的表观遗传联合疗法的前瞻性 2 期研究。
背景:外周T细胞淋巴瘤(PTCL)是典型的表观遗传恶性肿瘤,预后总是很差。需要新颖有效的治疗策略来改善临床预后,尤其是复发/难治患者的预后:我们开展了一项多中心2期研究,评估阿扎胞苷和千达酰胺单独或与吉西他滨和奥沙利铂(GemOx)联合治疗复发/难治性PTCL患者的疗效(注册号:ChiCTR2000037232)。主要终点是最佳总反应率:截至2024年5月1日,共有30名患者接受了疗效和毒性评估。最佳总体反应率为 53.3%,达到了主要终点。在血管免疫母细胞T细胞淋巴瘤(AITL;N = 19)患者中,与非AITL患者相比,无论是否联合化疗,都能观察到更高的应答率。中位随访时间为36.6个月,中位无进展生存期和总生存期分别为7.1个月和8.7个月。接受联合化疗的AITL患者(12人)取得了最理想的反应率(总反应率91.7%;完全缓解率66.7%)和生存率(中位无进展生存期17.2个月;中位总生存期38.8个月)。最常见的3-4级毒性反应是中性粒细胞减少(40.0%)和血小板减少(30.0%):结论:表观遗传学疗法与GemOx的联合治疗在复发/难治性PTCL患者中耐受性良好,疗效显著。尤其是AITL患者,可能会从这种联合治疗中获益更多,因此应成为未来研究的重点:本研究由江苏省自然科学基金(BK20232039)资助。
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来源期刊
Med
Med MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
17.70
自引率
0.60%
发文量
102
期刊介绍: Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.
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