School of Medicine, Baylor College of Medicine, Houston, Texas.
Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston.
JAMA Dermatol. 2017 Dec 1;153(12):1302-1306. doi: 10.1001/jamadermatol.2017.3593.
Brentuximab vedotin is a monomethyl auristatin E-conjugated monoclonal antibody directed against CD30. It represents a potential treatment for the CD30+ lymphoproliferative disorder lymphomatoid papulosis (LyP), which currently has no approved treatment.
To assess the efficacy and safety of brentuximab vedotin for the treatment of LyP.
DESIGN, SETTING, AND PARTICIPANTS: In this study conducted at The University of Texas MD Anderson Cancer Center from May 10, 2011, to March 31, 2017, a total of 12 patients with LyP received brentuximab vedotin. All patients were 18 years or older with a diagnosis of LyP and were also required to have scarring, more than 10 lesions, or active lesions on the face, hands, or feet. Nine patients were enrolled in a physician-initiated, open-label, single-center, phase 2 clinical trial of brentuximab vedotin for CD30+ cutaneous T-cell lymphomas and LyP from 2011 to 2013. Three patients were later treated outside of the trial from 2013 to 2017. Five patients continued to be followed up as of March 2017.
Intravenous brentuximab vedotin 1.8 mg/kg infused over 30 minutes every 21 days.
The primary end point was the overall response rate. Complete response was defined as zero lesions, and partial response was defined as a 50% or greater reduction in lesion count from baseline. A relapse was defined as loss of partial response.
All 12 patients (8 men and 4 women; median age, 46 years) responded to brentuximab vedotin, and 7 exhibited a complete response. Time to response was 3 weeks in all patients. The median duration of response was 20 weeks (range, 6-103 weeks). For 5 patients who relapsed, the median time to relapse was 12 weeks (range, 6-41 weeks). One patient who relapsed was retreated and has remained in partial response for more than 23 months. Grade 1 to 2 neuropathy occurred in 10 patients but resolved in 5. Adverse events of grade 3 or higher were neutropenia (n = 2) and dizziness/vertigo (n = 1). Three patients withdrew owing to adverse events.
Brentuximab vedotin is effective in treating LyP (overall response rate, 100%; complete response rate, 58%), but its use should be reserved for patients with truly severe and refractory LyP. More work is needed to optimize its dosing to minimize adverse events, such as peripheral neuropathy.
clinicaltrials.gov Identifier: NCT01352520.
Brentuximab vedotin 是一种针对 CD30 的单甲基奥瑞他汀 E 偶联的单克隆抗体。它代表了一种治疗 CD30+淋巴增生性疾病蕈样肉芽肿（LyP）的潜在治疗方法，目前尚无批准的治疗方法。
评估 Brentuximab vedotin 治疗 LyP 的疗效和安全性。
设计、地点和参与者： 本研究于 2011 年 5 月 10 日至 2017 年 3 月 31 日在德克萨斯大学 MD 安德森癌症中心进行，共有 12 例 LyP 患者接受了 Brentuximab vedotin 治疗。所有患者均为 18 岁或以上，诊断为 LyP，且需要有瘢痕、超过 10 个病变或面部、手部或脚部的活动性病变。9 例患者于 2011 年至 2013 年期间参加了 Brentuximab vedotin 治疗 CD30+皮肤 T 细胞淋巴瘤和 LyP 的医生发起的、开放标签、单中心、2 期临床试验。另外 3 例患者于 2013 年至 2017 年期间在试验之外接受治疗。截至 2017 年 3 月，有 5 例患者仍在随访中。
静脉内输注 1.8 mg/kg Brentuximab vedotin，每 21 天输注 30 分钟。
总体缓解率。完全缓解定义为零病变，部分缓解定义为病变计数比基线减少 50%或更多。复发定义为部分缓解丧失。
12 例患者（8 例男性和 4 例女性；中位年龄 46 岁）均对 Brentuximab vedotin 有反应，其中 7 例有完全缓解。所有患者的反应时间均为 3 周。缓解的中位持续时间为 20 周（范围 6-103 周）。5 例复发患者的中位复发时间为 12 周（范围 6-41 周）。1 例复发患者再次接受治疗，且已持续部分缓解超过 23 个月。10 例患者发生 1-2 级神经病变，但 5 例患者已缓解。3 级或更高级别的不良事件包括中性粒细胞减少症（n=2）和头晕/眩晕（n=1）。3 例患者因不良事件退出。
Brentuximab vedotin 治疗 LyP 有效（总缓解率为 100%；完全缓解率为 58%），但应保留用于真正严重和难治性 LyP 的患者。需要进一步研究来优化剂量以最小化外周神经病变等不良事件。
clinicaltrials.gov 标识符：NCT01352520。
