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

作者：Lin Gui, Junning Cao, Dongmei Ji, Huilai Zhang, Qian Fan, Jun Zhu, Yuqin Song, Shiyu Jiang, Zhiqiang Ning, Jia Yu, Yuankai Shi · 发表于：Chinese Journal of Cancer Research · 年份：2021 · DOI：10.21147/j.issn.1000-9604.2021.05.08 · 被引用次数：27 · 研究领域：Lymphoma Diagnosis and Treatment、T-cell and Retrovirus Studies、Histone Deacetylase Inhibitors Research

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 evaluab...