德国科隆大学医院Peter Borchmann团队比较了PET引导下BrECADD与eBEACOPP治疗晚期经典霍奇金淋巴瘤（HD21）的疗效和耐受性。相关论文于2024年7月3日发表在《柳叶刀》杂志上。

强化全身化疗对晚期经典霍奇金淋巴瘤具有最高的初级治愈率，但这需要付出严重且可能终身持续的毒性代价。通过布伦妥昔单抗-维多汀、依托泊苷、环磷酰胺、阿霉素、达卡巴嗪和地塞米松（BrECADD）的新方案，该研究旨在提高两个周期治疗后PET引导下晚期经典霍奇金淋巴瘤的风险效益比。

这项随机、多中心、平行、开放标签的3期临床试验在9个国家的233个试验点进行。符合条件的患者为成人（年龄≤60岁），患有新诊断的晚期经典霍奇金淋巴瘤（即Ann Arbor III/IV期、II期伴B症状，以及大纵隔肿块和结外病变的一个或两个危险因素）。患者被随机（1:1）分为四个或六个周期（21天间隔），分别递增剂量的依托泊苷（第1-3天静脉注射200 mg/m²）、阿霉素（第1天静脉注射35 mg/m²）和环磷酰胺（第1天静脉注射1250 mg/m²），以及标准剂量的博来霉素（第8天静脉注射10 mg/m²））、长春新碱（第8天静脉注射1.4 kg/m²）、普鲁卡因（第1-7天口服100 mg/m²）以及泼尼松（第1-14天口服40 mg/m²；eBEACOP）或BrECADD，两个周期后由PET引导。

患者和研究人员未双盲接受治疗分配。分级共同主要目标是显示（1）由治疗相关发病率定义的耐受性改善和（2）由无进展生存率定义的非劣效性，与eBEACOPP相比，BrECADD的绝对非劣效范围为6个百分点。如果确定了非劣效性，则需要进行无进展生存率优越性的额外测试。通过意向治疗进行分析；与治疗相关的发病率评估需要至少一个化疗周期的文件。

在2016年7月22日至2020年8月27日期间，共有1500名患者入组，其中749人被随机分配到BrECADD，751人被分配到eBEACOPP。1482名患者被纳入意向治疗分析。患者的中位年龄为31岁（IQR 24-42）。1482例患者中838例（56%）为男性，644例（44%）为女性。大多数患者是白人（1482人中有1352人[91%]）。

BrECADD的治疗相关发病率（738例患者中312例[42%]）显著低于eBEACOPP（732例患者中430例[59%]；相对风险0.72[95%CI 0.65–0.80]；p<0.0001）。在48个月的中位随访中，BrECADD改善了无进展生存率，风险比为0.66（0.45–0.97；p=0.035）；BrECADD和eBEACOPP的4年无进展生存率分别为94.3%（95%CI 92.6–96.1）和90.9%（88.7–93.1）。4年总生存率分别为98.6%（97.7–99.5）和98.2%（97.2–99.3）。

研究结果表明，在成人晚期经典霍奇金淋巴瘤的一线治疗中，两个周期后PET引导的BrECADD比eBEACOPP具有更好的耐受性和更有效的疗效。

附：英文原文

Title: Assessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma (HD21): a randomised, multicentre, parallel, open-label, phase 3 trial

Author: Peter Borchmann, Justin Ferdinandus, Gundolf Schneider, Alden Moccia, Richard Greil, Mark Hertzberg, Valdete Schaub, Andreas Hüttmann, Felix Keil, Judith Dierlamm, Mathias Hnel, Urban Novak, Julia Meissner, Andreas Zimmermann, Stephan Mathas, Josée M Zijlstra, Alexander Foss, Andreas Viardot, Bernd Hertenstein, Sonja Martin, Pratyush Giri, Sebastian Scholl, Max S Topp, Wolfram Jung, Vladan Vucinic, Hans-Joachim Beck, Andrea Kerkhoff, Benjamin Unger, Andreas Rank, Roland Schroers, Christian Meyer zum Büschenfelde, Maike de Wit, Karolin Trautmann-Grill, Peter Kamper, Daniel Molin, Stefanie Kreissl, Helen Kaul, Bastian von Tresckow, Sven Borchmann, Karolin Behringer, Michael Fuchs, Andreas Rosenwald, Wolfram Klapper, Hans-Theodor Eich, Christian Baues, Athanasios Zomas, Michael Hallek, Markus Dietlein, Carsten Kobe, Volker Diehl

Issue&Volume: 2024-07-03

Abstract:

Background

Intensified systemic chemotherapy has the highest primary cure rate for advanced-stage, classical Hodgkin lymphoma but this comes with a cost of severe and potentially life long, persisting toxicities. With the new regimen of brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD), we aimed to improve the risk-to-benefit ratio of treatment of advanced-stage, classical Hodgkin lymphoma guided by PET after two cycles.

Methods

This randomised, multicentre, parallel, open-label, phase 3 trial was done in 233 trial sites across nine countries. Eligible patients were adults (aged ≤60 years) with newly diagnosed, advanced-stage, classical Hodgkin lymphoma (ie, Ann Arbor stage III/IV, stage II with B symptoms, and either one or both risk factors of large mediastinal mass and extranodal lesions). Patients were randomly assigned (1:1) to four or six cycles (21-day intervals) of escalated doses of etoposide (200 mg/m2 intravenously on days 1–3), doxorubicin (35 mg/m2 intravenously on day 1), and cyclophosphamide (1250 mg/m2 intravenously on day 1), and standard doses of bleomycin (10 mg/m2 intravenously on day 8), vincristine (1·4 mg/m2 intravenously on day 8), procarbazine (100 mg/m2 orally on days 1–7), and prednisone (40 mg/m2 orally on days 1–14; eBEACOPP) or BrECADD, guided by PET after two cycles. Patients and investigators were not masked to treatment assignment. Hierarchical coprimary objectives were to show (1) improved tolerability defined by treatment-related morbidity and (2) non-inferior efficacy defined by progression-free survival with an absolute non-inferiority margin of 6 percentage points of BrECADD compared with eBEACOPP. An additional test of superiority of progression-free survival was to be done if non-inferiority had been established. Analyses were done by intention to treat; the treatment-related morbidity assessment required documentation of at least one chemotherapy cycle. This trial was registered at ClinicalTrials.gov (NCT02661503).

Findings

Between July 22, 2016, and Aug 27, 2020, 1500 patients were enrolled, of whom 749 were randomly assigned to BrECADD and 751 to eBEACOPP. 1482 patients were included in the intention-to-treat analysis. The median age of patients was 31 years (IQR 24–42). 838 (56%) of 1482 patients were male and 644 (44%) were female. Most patients were White (1352 [91%] of 1482). Treatment-related morbidity was significantly lower with BrECADD (312 [42%] of 738 patients) than with eBEACOPP (430 [59%] of 732 patients; relative risk 0·72 [95% CI 0·65–0·80]; p<0·0001). At a median follow-up of 48 months, BrECADD improved progression-free survival with a hazard ratio of 0·66 (0·45–0·97; p=0·035); 4-year progression-free survival estimates were 94·3% (95% CI 92·6–96·1) for BrECADD and 90·9% (88·7–93·1) for eBEACOPP. 4-year overall survival rates were 98·6% (97·7–99·5) and 98·2% (97·2–99·3), respectively.

Interpretation

BrECADD guided by PET after two cycles is better tolerated and more effective than eBEACOPP in first-line treatment of adult patients with advanced-stage, classical Hodgkin lymphoma.

DOI: 10.1016/S0140-6736(24)01315-1

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01315-1/abstract