贝林妥欧单抗联合 AVD 方案用于 II-IV 期 HIV 相关霍奇金淋巴瘤（AMC085）：一项开放标签、单臂、多中心 1/2 期临床试验的 2 期结果。
Brentuximab vedotin with AVD for stage II-IV HIV-related Hodgkin lymphoma (AMC 085): phase 2 results from an open-label, single arm, multicentre phase 1/2 trial.
机构信息
John H Stroger Jr Hospital of Cook County (Cook County Hospital), Section of Hematology/Oncology, Department of Medicine, Chicago, IL, USA; Ruth M Rothstein CORE Center, Chicago, IL, USA; University of Illinois, Chicago, Section of Hematology/Oncology, Department of Medicine, Chicago, IL, USA.
University of Arkansas for Medical Sciences, Little Rock, AR, USA.
出版信息
Lancet Haematol. 2023 Aug;10(8):e624-e632. doi: 10.1016/S2352-3026(23)00157-6.
BACKGROUND
Brentuximab vedotin in combination with doxorubicin, vinblastine, and dacarbazine (AVD) is approved in the upfront setting for advanced stage classical Hodgkin lymphoma (cHL). People living with HIV have been excluded from these studies. We aimed to understand the activity and safety of brentuximab vedotin-AVD in people living with HIV diagnosed with Hodgkin lymphoma, while focusing on HIV disease parameters and antiretroviral therapy (ART) interactions.
METHODS
We present the phase 2 portion of a multicentre phase 1/2 study. Eligible patients were 18 years or older, had untreated stage II-IV HIV-associated cHL (HIV-cHL), a Karnofsky performance status of more than 30%, a CD4 T-cell count of 50 cells per μL or more, were required to take ART, and were not on strong CYP3A4 or P-glycoprotein inhibitors. Patients were treated intravenously with 1·2 mg/kg of brentuximab vedotin (recommended phase 2 dose) with standard doses of AVD for six cycles on days 1 and 15 of a 28-day cycle. The primary endpoint of the phase 2 portion was 2-year progression-free survival (PFS), assessed in all eligible participants who began treatment. Accrual has been completed. This trial is registered at ClinicalTrials.gov, NCT01771107.
FINDINGS
Between March 8, 2013, and March 7, 2019, 41 patients received study therapy with a median follow up of 29 months (IQR 16-38). 34 (83%) of 41 patients presented with stage III-IV and seven (17%) with stage II unfavourable HIV-cHL. 37 (90%) of 41 patients completed therapy, all 37 of whom achieved complete response. The 2-year PFS was 87% (95% CI 71-94) and the overall survival was 92% (78-97). The most common grade 3 or worse adverse events were peripheral sensory neuropathy (four [10%] of 41 patients), neutropenia (18 [44%]), and febrile neutropenia (five [12%]). One treatment-related death was reported, due to infection.
INTERPRETATION
Brentuximab vedotin-AVD was highly active and had a tolerable adverse event rate in HIV-cHL and is an important therapeutic option for people with HIV-cHL. The complete reponse rate is encouraging and is possibly related to a unique aspect of HIV-cHL biology. Upcoming 5-year data will evaluate the sustainability of the outcomes obtained.
FUNDING
National Institutes of Health and National Cancer Institute.
背景
贝林妥欧单抗与多柔比星、长春碱和达卡巴嗪（AVD）联合用于治疗晚期经典霍奇金淋巴瘤（cHL）的一线治疗。这些研究排除了艾滋病毒感染者。本研究旨在了解贝林妥欧单抗-AVD 对诊断为霍奇金淋巴瘤的 HIV 感染者的疗效和安全性，同时重点关注 HIV 疾病参数和抗逆转录病毒治疗（ART）的相互作用。
方法
我们报告了这项多中心 1/2 期研究的 2 期部分。纳入标准为年龄 18 岁或以上、未经治疗的 II-IV 期 HIV 相关 cHL（HIV-cHL）、卡氏功能状态评分大于 30%、CD4 T 细胞计数大于 50 个/μL、需要接受 ART 治疗且未使用强 CYP3A4 或 P-糖蛋白抑制剂。患者接受 1.2mg/kg 的贝林妥欧单抗静脉注射（推荐的 2 期剂量），联合 AVD 标准剂量，每 28 天周期的第 1 天和第 15 天用药 6 个周期。2 期部分的主要终点是所有开始治疗的合格参与者的 2 年无进展生存（PFS）。该试验已在 ClinicalTrials.gov 上注册，编号为 NCT01771107。
结果
2013 年 3 月 8 日至 2019 年 3 月 7 日，41 例患者接受了研究治疗，中位随访时间为 29 个月（IQR 16-38）。41 例患者中 34 例（83%）为 III-IV 期，7 例（17%）为 II 期不良预后 HIV-cHL。41 例患者中 37 例（90%）完成了治疗，所有 37 例患者均达到完全缓解。2 年 PFS 为 87%（95%CI 71-94），总生存率为 92%（78-97）。最常见的 3 级或更高级别的不良事件为周围感觉神经病（41 例患者中有 4 例[10%]）、中性粒细胞减少（18 例[44%]）和发热性中性粒细胞减少（5 例[12%]）。1 例治疗相关死亡报告为感染。
结论
贝林妥欧单抗-AVD 在 HIV-cHL 中具有高度活性和可耐受的不良事件发生率，是治疗 HIV-cHL 患者的重要治疗选择。完全缓解率令人鼓舞，可能与 HIV-cHL 生物学的一个独特方面有关。即将进行的 5 年数据将评估所获得结果的可持续性。
资助
美国国立卫生研究院和美国国家癌症研究所。
Zotero 插件