Treatment options for stage I/II bulky and advanced-stage disease have recently extensively changed. For decades in North America, ABVD (doxorubicin hydrochloride [Adriamycin], bleomycin sulfate, vinblastine sulfate, and dacarbazine) has been a frontline standard-of-care option for patients with advanced classical Hodgkin lymphoma (cHL). Recent data on combining brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine demonstrated improved overall survival compared with ABVD but increased adverse events (AEs). We hypothesized that replacing vinblastine with nivolumab (brentuximab vedotin and nivolumab [AN] + doxorubicin and dacarbazine [AD]; AN+AD) may improve efficacy and safety. This phase 2, open-label multipart, multicenter study enrolled patients with treatment-naive stage II bulky or III/IV cHL. Patients received ≤6 cycles of AN+AD; granulocyte-colony stimulating factor (G-CSF) prophylaxis was optional, per institutional guidelines. At the time of planned analysis (N = 57), complete response (CR) and objective response rates were 88% (95% confidence interval [CI], 76.3-94.9) and 93% (95% CI, 83.0-98.1), respectively. With a median follow-up of 24.2 months (95% CI, 23.4-26.9), the 2-year progression-free survival rate was 88% (95% CI, 75.7-94.6); 88% (95% CI, 75.7-94.6) had a response lasting >2 years. Most common grade ≥3 treatment-related AEs were alanine aminotransferase increased (11%) and neutropenia (9%); 44% had treatment-related peripheral sensory neuropathy (grade 1/2, 40%; grade 3, 4%). No febrile neutropenia occurred; 49% received G-CSF prophylaxis. AN+AD led to a high CR rate and favorable safety profile. Further evaluation of programmed death receptor 1 inhibitor and CD30 antibody–drug conjugate combination regimens in frontline advanced-stage cHL is warranted. This trial was registered at www.clinicaltrials.gov as #NCT03646123 and www.clinicaltrialsregister.eu as #EudraCT 2020-004027-17.

中文翻译：

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Brentuximab vedotin、纳武利尤单抗、多柔比星和达卡巴嗪治疗晚期经典霍奇金淋巴瘤


I/II 期、大块和晚期疾病的治疗选择最近发生了广泛变化。几十年来，ABVD（盐酸阿霉素 [阿霉素]、硫酸博来霉素、硫酸长春碱和达卡巴嗪）一直是晚期经典霍奇金淋巴瘤 （cHL） 患者的一线标准治疗选择。最近关于 brentuximab vedotin、多柔比星、长春碱和达卡巴嗪联合用药的数据显示，与 ABVD 相比，总生存期更高，但不良事件 （AE） 增加。我们假设用纳武利尤单抗替代长春碱（brentuximab vedotin 和 nivolumab [AN] + 阿霉素和达卡巴嗪 [AD];AN+AD） 可能会提高疗效和安全性。这项 2 期、开放标签、多部分、多中心研究招募了未接受过治疗的 II 期大块或 III/IV 期 cHL 患者。患者接受 ≤6 个周期的 AN+AD;根据机构指南，粒细胞集落刺激因子 （G-CSF） 预防是可选的。在计划分析时 （N = 57），完全缓解 （CR） 和客观缓解率分别为 88% （95% 置信区间 [CI]，76.3-94.9） 和 93% （95% CI，83.0-98.1）。中位随访 24.2 个月 （95% CI，23.4-26.9），2 年无进展生存率为 88% （95% CI，75.7-94.6）;88% （95% CI，75.7-94.6） 的反应持续 >2 年。最常见的 ≥3 级治疗相关 AE 是丙氨酸氨基转移酶升高 （11%） 和中性粒细胞减少症 （9%）;44% 患有治疗相关的周围感觉神经病变 （1/2 级，40%;3 级，4%）。未发生发热性中性粒细胞减少症;49% 接受了 G-CSF 预防。AN+AD 导致高 CR 率和良好的安全性。 有必要进一步评估程序性死亡受体 1 抑制剂和 CD30 抗体-药物偶联物联合方案在一线晚期 cHL 中的疗效。该试验在 www.clinicaltrials.gov 注册为 #NCT03646123，www.clinicaltrialsregister.eu 注册为 #EudraCT 2020-004027-17。