Brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine for advanced-stage classical Hodgkin lymphoma.

IF 21 1区医学 Q1 HEMATOLOGY

Blood Pub Date : 2025-01-16 DOI:10.1182/blood.2024024681

Hun Ju Lee, Rod Ramchandren, Judah Friedman, Jason Melear, Ian W Flinn, John M Burke, Yuliya Linhares, Paul Gonzales, Matthew Peterson, Mihir Raval, Rangaswamy Chintapatla, Tatyana A Feldman, Habte Yimer, Miguel Islas-Ohlmayer, Ameet Patel, Leland Metheny, Asad Dean, Vishal Rana, Mitul D Gandhi, John Renshaw, Linda Ho, Michelle A Fanale, Wenchuan Guo, Christopher A Yasenchak

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引用次数: 0

Abstract

Abstract: 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.

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Brentuximab Vedotin, Nivolumab，阿霉素和达卡巴嗪治疗晚期经典霍奇金淋巴瘤。

I/II期大体积和晚期疾病的治疗方案最近发生了广泛的变化。几十年来，ABVD一直是北美晚期经典霍奇金淋巴瘤（cHL）患者的一线标准治疗选择。最近的数据显示，与ABVD相比，brentuximab vedotin、阿霉素、长春花碱和达卡巴嗪联合治疗的总生存率提高，但不良事件（ae）增加。我们假设用纳武单抗（AN+AD）替代长春花碱可能提高疗效和安全性。这项2期、开放标签、多部分、多中心研究纳入了未接受治疗的II期大体积或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% 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至26.9），2年PFS率为88% (95% CI， 75.7至94.6)；88% （95% CI, 75.7 ~ 94.6）患者的缓解持续了10 ~ 2年。最常见的≥3级治疗相关ae是丙氨酸转氨酶升高（11%）和中性粒细胞减少（9%）；44%有治疗相关的周围感觉神经病变(1/2级，40%；等级3,4%)。无发热性中性粒细胞减少；49%接受了G-CSF预防。AN+AD导致高CR率和良好的安全性。程序性死亡受体1抑制剂和CD30抗体-药物结合治疗一线晚期cHL有必要进行进一步评估。试验注册：NCT03646123。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Blood 医学-血液学

CiteScore

23.60

自引率

3.90%

发文量

955

审稿时长

1 months

期刊介绍： Blood, the official journal of the American Society of Hematology, published online and in print, provides an international forum for the publication of original articles describing basic laboratory, translational, and clinical investigations in hematology. Primary research articles will be published under the following scientific categories: Clinical Trials and Observations; Gene Therapy; Hematopoiesis and Stem Cells; Immunobiology and Immunotherapy scope; Myeloid Neoplasia; Lymphoid Neoplasia; Phagocytes, Granulocytes and Myelopoiesis; Platelets and Thrombopoiesis; Red Cells, Iron and Erythropoiesis; Thrombosis and Hemostasis; Transfusion Medicine; Transplantation; and Vascular Biology. Papers can be listed under more than one category as appropriate.