Chidamide combined with cyclophosphamide, doxorubicin, vincristine and prednisone in previously untreated patients with peripheral T-cell lymphoma.

Lin Gui, Junning Cao, Dongmei Ji, Huilai Zhang, Qian Fan, Jun Zhu, Yuqin Song, Shiyu Jiang, Zhiqiang Ning, Jia Yu, Yuankai Shi
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引用次数: 11

Abstract

Objective: Chidamide is an oral histone deacetylase subtype-selective inhibitor approved for relapsed or refractory peripheral T-cell lymphoma (PTCL). This phase 1b study evaluated the safety, pharmacokinetics, and preliminary efficacy of chidamide in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) for treatment-naïve PTCL patients.

Methods: This study was an open-label, multicenter trial composed of dose escalation and dose expansion. Patients received CHOP for six 21-d cycles and chidamide on d 1, 4, 8 and 11 in each cycle. Four dose levels of chidamide (20, 25, 30 and 35 mg) were evaluated. The primary objective was to evaluate the safety and tolerability of the combination regimen.

Results: A total of 30 patients were evaluated in this study: 15 in the dose-escalation part and 15 in the dose-expansion part. In the dose-escalation study, three patients were enrolled in the 35 mg chidamide cohort. One had dose-limiting toxicity with grade 3 vascular access complications, and one had grade 2 neutropenia with a sustained temperature >38 °C. Dose escalation was stopped at this chidamide dose level. The most common (≥10%) grade 3 or 4 adverse events (AEs) were leukopenia (90.0%), neutropenia (83.3%), vomiting (13.3%), thrombocytopenia (10.0%) and febrile neutropenia (10.0%). No significant changes in chidamide pharmacokinetic properties were observed before and after combination treatment. The objective response rate for the 28 patients evaluable for preliminary efficacy was 89.3% (25/28), with 16 (57.1%) achieving complete response or unconfirmed complete response. The estimated median progression-free survival was 14.0 months. In summary, we chose chidamide 30 mg as the recommended dose for phase 2.

Conclusions: The addition of chidamide to standard CHOP chemotherapy was tolerable with promising preliminary efficacy in previously untreated PTCL patients, which supports further clinical studies with this combination regimen for the frontline treatment of PTCL.

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奇达胺联合环磷酰胺、阿霉素、长春新碱和强的松治疗未经治疗的周围t细胞淋巴瘤患者。
目的:Chidamide是一种口服组蛋白去乙酰化酶亚型选择性抑制剂,被批准用于复发或难治性外周t细胞淋巴瘤(PTCL)。这项1b期研究评估了奇达胺与环磷酰胺、阿霉素、长春新碱和泼尼松(CHOP)联合治疗treatment-naïve PTCL患者的安全性、药代动力学和初步疗效。方法:本研究是一项开放标签、多中心试验,由剂量递增和剂量扩展组成。患者接受6个21 d周期的CHOP治疗,并在每个周期的第1、4、8和11天接受奇达胺治疗。评估了四种剂量水平(20、25、30和35 mg)。主要目的是评估联合治疗方案的安全性和耐受性。结果:本研究共评估了30例患者:剂量递增部分15例,剂量扩展部分15例。在剂量递增研究中,有3名患者被纳入35 mg噻丁胺组。1例有剂量限制性毒性,伴有3级血管通路并发症,1例有2级中性粒细胞减少,持续温度>38°C。剂量递增在此剂量水平停止。最常见(≥10%)的3级或4级不良事件(ae)是白细胞减少(90.0%)、中性粒细胞减少(83.3%)、呕吐(13.3%)、血小板减少(10.0%)和发热性中性粒细胞减少(10.0%)。复方用药前后患儿药代动力学性质无明显变化。可评估初步疗效的28例患者的客观缓解率为89.3%(25/28),其中16例(57.1%)达到完全缓解或未证实完全缓解。估计中位无进展生存期为14.0个月。综上所述,我们选择齐达胺30mg作为第二阶段的推荐剂量。结论:对于先前未接受治疗的PTCL患者,在标准CHOP化疗方案中添加奇达胺是可耐受的,并且具有良好的初步疗效,这支持了将该联合方案用于PTCL一线治疗的进一步临床研究。
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