靶向药物联合CHOP方案与CHOP方案作为初治外周T细胞淋巴瘤患者一线治疗的比较（GUIDANCE-03）：一项开放标签、多中心2期临床试验
Targeted agents plus CHOP compared with CHOP as the first-line treatment for newly diagnosed patients with peripheral T-cell lymphoma (GUIDANCE-03): an open-label, multicentre phase 2 clinical trial.
作者信息
Cai Ming-Ci, Cheng Shu, Jing Hong-Mei, Liu Yan, Cui Guo-Hui, Niu Ting, Shen Jian-Zhen, Huang Liang, Wang Xin, Huang Yao-Hui, Wang Li, Xu Peng-Peng, Zhao Wei-Li
机构信息
Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Hematology, Lymphoma Research Center, Peking University Third Hospital, Beijing, China.
出版信息
Lancet Reg Health West Pac. 2024 Jul 29;50:101160. doi: 10.1016/j.lanwpc.2024.101160. eCollection 2024 Sep.
BACKGROUND
Peripheral T-cell lymphoma (PTCL) is a heterogeneous disease with dismal outcomes. We conducted an open-label, phase 2 nonrandomised, externally controlled study to evaluate the efficacy and safety of targeted agents plus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) (CHOPX) for PTCL in the front-line setting.
METHODS
Eligible patients were ≥18 years of age and newly diagnosed PTCL. Patients in the CHOPX group received standard CHOP at Cycle 1. Specific targeted agents were added from Cycle 2, decitabine if , azacytidine if , tucidinostat if , and lenalidomide if without mutations above. Patients in the CHOP group received CHOP for 6 cycles. The primary endpoint was the complete response rate (CRR) at the end of treatment (EOT). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. The study was registered with ClinicalTrials.gov, NCT04480099.
FINDINGS
Between July 29, 2020, and Sep 22, 2022, 96 patients were enrolled and included for efficacy and safety analysis with 48 in each group. The study met its primary endpoint. CRR at EOT in the CHOPX group was superior to the CHOP group (64.6% vs. 33.3%, OR 0.27, 95%CI 0.12-0.64; = 0.004). At a median follow-up of 24.3 months (IQR 12.0-26.7), improved median PFS was observed in the CHOPX group (25.5 vs. 9.0 months; HR 0.57, 95%CI 0.34-0.98; = 0.041). The median OS was similar between two groups (not reached vs. 30.9 months; HR 0.55, 95%CI 0.28-1.10; = 0.088). The most common grade 3-4 hematological and non-hematological adverse events in the CHOPX group were neutropenia (31, 65%) and infection (5, 10%).
INTERPRETATION
Targeted agents combined with CHOP demonstrated effective and safe as first-line treatment in PTCL. Biomarker-driven therapeutic strategy is feasible and may lead to promising efficacy specifically toward molecular features in PTCL.
FUNDING
This study was supported by the National Key Research and Development Program (2022YFC2502600) and the General Program of the Shanghai Municipal Health Commission (202040400).
背景
外周T细胞淋巴瘤（PTCL）是一种预后不佳的异质性疾病。我们开展了一项开放标签、2期非随机、外部对照研究，以评估一线治疗中靶向药物联合CHOP（环磷酰胺、阿霉素、长春新碱和泼尼松）（CHOPX）方案治疗PTCL的疗效和安全性。
方法
符合条件的患者年龄≥18岁且为新诊断的PTCL。CHOPX组患者在第1周期接受标准CHOP方案治疗。从第2周期开始添加特定的靶向药物，若 则添加地西他滨，若 则添加阿扎胞苷，若 则添加图西诺司他，若无上述突变则添加来那度胺。CHOP组患者接受6周期CHOP方案治疗。主要终点为治疗结束时（EOT）的完全缓解率（CRR）。次要终点包括总缓解率（ORR）、无进展生存期（PFS）、总生存期（OS）和安全性。该研究已在ClinicalTrials.gov注册，注册号为NCT04480099。
结果
在2020年7月29日至2022年9月22日期间，共纳入96例患者并进行疗效和安全性分析，每组48例。该研究达到了主要终点。CHOPX组EOT时的CRR优于CHOP组（64.6%对33.3%，OR 0.27，95%CI 0.12 - 0.64；P = 0.004）。在中位随访24.3个月（IQR 12.0 - 26.7）时，CHOPX组的中位PFS有所改善（25.5个月对9.0个月；HR 0.57，95%CI 0.34 - 0.98；P = 0.041）。两组的中位OS相似（未达到对30.9个月；HR 0.55，95%CI 0.28 - 1.10；P = 0.088）。CHOPX组最常见的3 - 4级血液学和非血液学不良事件为中性粒细胞减少（31例，65%）和感染（5例，10%）。
解读
靶向药物联合CHOP方案作为PTCL的一线治疗有效且安全。生物标志物驱动的治疗策略是可行的，可能会针对PTCL的分子特征产生有前景的疗效。
资助
本研究由国家重点研发计划（2022YFC2502600）和上海市卫生健康委员会一般项目（202040400）资助。
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