Zhang Wei, Su Liping, Liu Lihong, Gao Yuhuan, Wang Quanshun, Su Hang, Song Yuhuan, Zhang Huilai, Shen Jing, Jing Hongmei, Wang Shuye, Cen Xinan, Liu Hui, Liu Aichun, Li Zengjun, Luo Jianmin, He Jianxia, Wang Jingwen, O'Connor O A, Zhou Daobin
Department of Hematology, Peking Union Medical College Hospital, Beijing 100730, China.
Department of Hematology, Shanxi Provincial Cancer Hospital, Taiyuan 030013, China.
Cancer Biol Med. 2021 Mar 23;18(3):841-8. doi: 10.20892/j.issn.2095-3941.2020.0413.
To assess the efficacy and safety of the novel histone deacetylase inhibitor, chidamide, in combination with cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (Chi-CHOEP) for untreated peripheral T-cell lymphoma (PTCL).
A prospective, multicenter, single arm, phase 1b/2 study was conducted. A total of 128 patients with untreated PTCL (18-70 years of age) were enrolled between March 2016 and November 2019, and treated with up to 6 cycles with the Chi-CHOEP regimen. In the phase 1b study, 3 dose levels of chidamide were evaluated and the primary endpoint was determination of the maximum-tolerated dose and recommended phase 2 dose (RP2D). The primary endpoint of the phase 2 study was 2-year progression-free survival (PFS).
Fifteen patients were enrolled in the phase 1b study and the RP2D for chidamide was determined to be 20 mg, twice a week. A total of 113 patients were treated at the RP2D in the phase 2 study, and the overall response rate was 60.2%, with a complete response rate of 40.7%. At a median follow-up of 36 months, the median PFS was 10.7 months, with 1-, 2-, and 3-year PFS rates of 49.9%, 38.0%, and 32.8%, respectively. The Chi-CHOEP regimen was well-tolerated, with grade 3/4 neutropenia occurring in approximately two-thirds of the patients. No unexpected adverse events (AEs) were reported and the observed AEs were manageable.
This large cohort phase 1b/2 study showed that Chi-CHOEP was well-tolerated with modest efficacy in previously untreated PTCL patients.
评估新型组蛋白去乙酰化酶抑制剂西达本胺联合环磷酰胺、多柔比星、长春新碱、依托泊苷及泼尼松（Chi-CHOEP方案）治疗初治外周T细胞淋巴瘤（PTCL）的疗效和安全性。
开展一项前瞻性、多中心、单臂1b/2期研究。2016年3月至2019年11月期间，共纳入128例年龄在18至70岁的初治PTCL患者，接受Chi-CHOEP方案治疗，最多6个周期。在1b期研究中，评估了3个西达本胺剂量水平，主要终点是确定最大耐受剂量和推荐的2期剂量（RP2D）。2期研究的主要终点是2年无进展生存期（PFS）。
1b期研究纳入了15例患者，确定西达本胺的RP2D为20 mg，每周两次。2期研究中共有113例患者接受RP2D治疗，总缓解率为60.2%，完全缓解率为40.7%。中位随访36个月时，中位PFS为10.7个月，1年、2年和3年PFS率分别为49.9%、38.0%和32.8%。Chi-CHOEP方案耐受性良好，约三分之二的患者出现3/4级中性粒细胞减少。未报告意外不良事件（AE），观察到的AE可管理。
这项大型队列1b/2期研究表明，Chi-CHOEP方案耐受性良好，对既往未治疗的PTCL患者有一定疗效。
