美国梅奥诊所Stephen M. Ansell团队研究了本妥昔单抗治疗Ⅲ期或Ⅳ期霍奇金淋巴瘤的总生存率。2022年7月13日出版的《新英格兰医学杂志》发表了这项成果。

一项研究显示，与阿霉素、博莱霉素、长春碱和达卡巴嗪（ABVD）相比，使用本妥昔单抗（brentuximab vedotin，一种CD30定向抗体-药物偶联物）联合阿霉素、长春碱和达卡巴嗪（A+AVD）一线治疗先前未经治疗的III或IV期经典霍奇金淋巴瘤患者，随访5年后显示可获得长期无进展生存益处。该研究中期分析表明对总体生存率有潜在益处；现在可以获得6年随访的中位数数据。

研究组以1:1的比例随机分配患者接受最多六个周期的A+AVD或ABVD。主要终点为改良无进展生存率，此前已有报道。关键次要终点是意向治疗人群的总生存率。还评估了安全性。

共有664名患者接受A+AVD治疗，670名患者接受ABVD治疗。在平均73.0个月的随访中，A+AVD组中有39名患者死亡，显著少于ABVD组的64名，危险比为0.59。A+AVD组6年总生存率估计为93.9%，ABVD组为89.4%。与ABVD组相比，A+AVD组患者的无进展生存期更长，疾病进展或死亡的风险比为0.68。

与ABVD组相比，A+AVD组需要接受后续治疗（包括移植）的患者更少，并且A+AVD组报告的二次患癌数更少，分别为23例与32例患者。在A+AVD组中观察到发热性中性粒细胞减少症的发病率增加后，研究组建议使用粒细胞集落刺激因子进行一级预防。与ABVD组患者相比，A+AVD组患者的周围神经病变更多，但两组中的大多数患者在最后一次随访时不良事件已缓解或改善。

研究结果表明，与接受ABVD治疗相比，接受A+AVD治疗的III期或IV期霍奇金淋巴瘤的患者具有更大的生存优势。

附：英文原文

Title: Overall Survival with Brentuximab Vedotin in Stage III or IV Hodgkin’s Lymphoma

Author: Stephen M. Ansell, M.D., Ph.D.,, John Radford, M.D.,, Joseph M. Connors, M.D.,, Monika Dugosz-Danecka, M.D., Ph.D.,, Won-Seog Kim, M.D.,, Andrea Gallamini, M.D.,, Radhakrishnan Ramchandren, M.D.,, Jonathan W. Friedberg, M.D.,, Ranjana Advani, M.D.,, Martin Hutchings, Ph.D.,, Andrew M. Evens, D.O.,, Piotr Smolewski, M.D., Ph.D.,, Kerry J. Savage, M.D.,, Nancy L. Bartlett, M.D.,, Hyeon-Seok Eom, M.D., Ph.D.,, Jeremy S. Abramson, M.D.,, Cassie Dong, Ph.D.,, Frank Campana, M.D.,, Keenan Fenton, M.D.,, Markus Puhlmann, M.D.,, and David J. Straus, M.D.

Issue&Volume: 2022-07-13

Abstract:

Background

Five-year follow-up in a trial involving patients with previously untreated stage III or IV classic Hodgkin’s lymphoma showed long-term progression-free survival benefits with first-line therapy with brentuximab vedotin, a CD30-directed antibody–drug conjugate, plus doxorubicin, vinblastine, and dacarbazine (A+AVD), as compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). A planned interim analysis indicated a potential benefit with regard to overall survival; data from a median of 6 years of follow-up are now available.

Methods

We randomly assigned patients in a 1:1 ratio to receive up to six cycles of A+AVD or ABVD. The primary end point, modified progression-free survival, has been reported previously. The key secondary end point was overall survival in the intention-to-treat population. Safety was also assessed.

Results

A total of 664 patients were assigned to receive A+AVD and 670 to receive ABVD. At a median follow-up of 73.0 months, 39 patients in the A+AVD group and 64 in the ABVD group had died (hazard ratio, 0.59; 95% confidence interval [CI], 0.40 to 0.88; P=0.009). The 6-year overall survival estimates were 93.9% (95% CI, 91.6 to 95.5) in the A+AVD group and 89.4% (95% CI, 86.6 to 91.7) in the ABVD group. Progression-free survival was longer with A+AVD than with ABVD (hazard ratio for disease progression or death, 0.68; 95% CI, 0.53 to 0.86). Fewer patients in the A+AVD group than in the ABVD group received subsequent therapy, including transplantation, and fewer second cancers were reported with A+AVD (in 23 vs. 32 patients). Primary prophylaxis with granulocyte colony-stimulating factor was recommended after an increased incidence of febrile neutropenia was observed with A+AVD. More patients had peripheral neuropathy with A+AVD than with ABVD, but most patients in the two groups had resolution or amelioration of the event by the last follow-up.

Conclusions

Patients who received A+AVD for the treatment of stage III or IV Hodgkin’s lymphoma had a survival advantage over those who received ABVD.

DOI: 10.1056/NEJMoa2206125

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2206125