PDF(Pubmed)
Abstract：
OBJECTIVE: 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).
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: This large cohort phase 1b/2 study showed that Chi-CHOEP was well-tolerated with modest efficacy in previously untreated PTCL patients.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: This large cohort phase 1b/2 study showed that Chi-CHOEP was well-tolerated with modest efficacy in previously untreated PTCL patients.
摘要：
目的：为了评估新型组蛋白去乙酰化酶抑制剂的疗效和安全性，西达胺,结合环磷酰胺，阿霉素,长春新碱,依托泊苷,和泼尼松（Chi-CHOEP）治疗未经治疗的外周T细胞淋巴瘤（PTCL）。
方法：前瞻性，多中心，单臂,进行了1b/2期研究。2016年3月至2019年11月，共纳入128例未经治疗的PTCL患者（18-70岁），并采用Chi-CHOEP方案治疗6个周期。在1b期研究中，评估西达本胺的3个剂量水平，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）。
结果：1b期研究纳入了15例患者，西达本胺的RP2D测定为20mg，一周两次.在2期研究中，共有113名患者在RP2D接受治疗，总有效率为60.2%,完全缓解率为40.7%。在中位随访36个月时，中位PFS为10.7个月,1-,2-,3年PFS率为49.9%，38.0%,和32.8%，分别。Chi-CHOEP方案耐受性良好，大约三分之二的患者发生3/4级中性粒细胞减少症。未报告意外不良事件（AE），观察到的AE是可控的。
结论：这项大型队列1b/2期研究表明，Chi-CHOEP在先前未经治疗的PTCL患者中具有良好的耐受性，且疗效适中。
方法：前瞻性，多中心，单臂,进行了1b/2期研究。2016年3月至2019年11月，共纳入128例未经治疗的PTCL患者（18-70岁），并采用Chi-CHOEP方案治疗6个周期。在1b期研究中，评估西达本胺的3个剂量水平，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）。
结果：1b期研究纳入了15例患者，西达本胺的RP2D测定为20mg，一周两次.在2期研究中，共有113名患者在RP2D接受治疗，总有效率为60.2%,完全缓解率为40.7%。在中位随访36个月时，中位PFS为10.7个月,1-,2-,3年PFS率为49.9%，38.0%,和32.8%，分别。Chi-CHOEP方案耐受性良好，大约三分之二的患者发生3/4级中性粒细胞减少症。未报告意外不良事件（AE），观察到的AE是可控的。
结论：这项大型队列1b/2期研究表明，Chi-CHOEP在先前未经治疗的PTCL患者中具有良好的耐受性，且疗效适中。
