Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230031, China; Department of Hematology, Anhui Provincial Cancer Hospital, Hefei, Anhui 230031, China.
Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu 210029, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Med. 2024 Nov 8;5(11):1393-1401.e2. doi: 10.1016/j.medj.2024.07.007. Epub 2024 Jul 30.
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).
外周 T 细胞淋巴瘤（PTCLs）是典型的表观遗传学恶性肿瘤，预后普遍较差。需要新的、有效的治疗策略来改善临床结果，特别是在复发/难治性患者中。
我们进行了一项多中心 2 期研究，以评估阿扎胞苷和西达本胺单独或联合吉西他滨和奥沙利铂（GemOx）在复发/难治性 PTCL 患者中的治疗效果（注册号：ChiCTR2000037232）。主要终点是最佳总缓解率。
截至 2024 年 5 月 1 日，30 名患者可评估疗效和毒性。最佳总缓解率为 53.3%，达到了主要终点。在血管免疫母细胞性 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，观察到更高的反应率。中位随访 36.6 个月后，中位无进展生存期和总生存期分别为 7.1 和 8.7 个月。接受联合化疗的 AITL 患者（N=12）获得了最有希望的缓解率（总缓解率，91.7%；完全缓解率，66.7%）和生存结果（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 级毒性是中性粒细胞减少（40.0%）和血小板减少（30.0%）。
表观遗传学治疗联合 GemOx 在复发/难治性 PTCL 患者中耐受良好且疗效显著。特别是 AITL 患者可能从这种联合治疗中获益更多，应成为未来研究的重点。
本工作得到江苏省自然科学基金（BK20232039）的资助。
