Servicio de Hematología, Hospital Universitario de Salamanca; Instituto de Investigación Biomédica de Salamanca (IBSAL); Centro de Investigación del Cáncer de Salamanca, Salamanca; Servicio de Hematología, Hospital Duran i Reynals, Instituto Catalá d'Oncologia, L'Hospitalet de Llobregat, Barcelona.
Servicio de Hematología, Hospital Virgen del Rocio de Sevilla, Seville.
Ann Oncol. 2019 Apr 1;30(4):612-620. doi: 10.1093/annonc/mdz009.
In this work, we assessed the efficacy and safety of brentuximab vedotin (BV) plus ESHAP (BRESHAP) as second-line therapy for Relapsed/Refractory Hodgkin lymphoma (RRHL) to improve the results before autologous stem-cell transplantation (ASCT).
This was a multicenter, open-label, phase I-II trial of patients with RRHL after first-line chemotherapy. Treatment had three 21-day cycles of etoposide, solumedrol, high-dose AraC, and cisplatin. BV was administered at three dose levels (0.9, 1.2, and 1.8 mg/kg) intravenous on day ‒1 to 3 + 3 cohorts of patients. Final BV dose was 1.8 mg/kg. Responding patients proceeded to ASCT, followed by three BV courses (1.8 mg/kg, every 21 days). Main end points for evaluation were maximum tolerable dose and overall and complete response (CR) before ASCT.
A total of 66 patients were recruited (median age 36 years; range 18-66): 40 were primary refractory, 16 early relapse and 10 late relapse. There were 39 severe adverse events were reported in 22 patients, most frequently fever (n = 25, 35% neutropenic), including 3 deaths. Grade 3-4 hematological toxicity presented in 28 cases: neutropenia (n = 21), thrombocytopenia (n = 14), and anemia (n = 7). Grade ≥3-4 extrahematological adverse events (≥5%) were non-neutropenic fever (n = 13) and hypomagnesaemia (n = 3). Sixty-four patients underwent stem-cell mobilization; all collected >2×10e6/kg CD34+ cells (median 5.75; range 2.12-33.4). Overall response before transplant was 91% (CI 84% to 98%), including 70% (CRs 95% CI 59% to 81%). 60 patients were transplanted with no failure engraftments. Post-transplant response was CR in 49 patients (82% CI 73% to 91%) and partial responses in six (10% CI 5% to 15%). After a mean follow-up of 27 months, the 30-month time to treatment to failure was 74% (95% CI 68% to 80%), progression-free survival 71% (95% CI 65% to 77%), and overall survival 91% (CI 84% to 98%).
BRESHAP looks a safe and effective pre-transplant induction regimen, does not jeopardize transplant and allows long-term remissions and survival.
在这项工作中，我们评估了 Brentuximab vedotin（BV）联合ESHAP（BRESHAP）作为二线治疗方案在复发/难治性霍奇金淋巴瘤（RRHL）患者中的疗效和安全性，以改善自体造血干细胞移植（ASCT）前的结果。
这是一项多中心、开放标签、I/II 期试验，纳入了一线化疗后 RRHL 的患者。治疗方案包括三个 21 天周期的依托泊苷、甲泼尼龙、高剂量阿糖胞苷和顺铂。BV 以三种剂量水平（0.9、1.2 和 1.8mg/kg）在第-1 天至 3 天静脉给药，共三个剂量水平，每组有 3 名患者。最终的 BV 剂量为 1.8mg/kg。有缓解的患者继续接受 ASCT，随后接受三个 BV 疗程（1.8mg/kg，每 21 天一次）。主要评估终点为最大耐受剂量和 ASCT 前的总体缓解率和完全缓解率。
共招募了 66 名患者（中位年龄 36 岁；范围 18-66 岁）：40 名患者为原发性耐药，16 名患者为早期复发，10 名患者为晚期复发。22 名患者报告了 39 起严重不良事件，最常见的是发热（n=25，35%为中性粒细胞减少性发热），包括 3 例死亡。28 例出现 3-4 级血液学毒性：中性粒细胞减少（n=21）、血小板减少（n=14）和贫血（n=7）。3-4 级非血液学不良事件（≥5%）为非中性粒细胞减少性发热（n=13）和低镁血症（n=3）。64 名患者进行了干细胞动员；所有患者均采集了>2×10e6/kg CD34+细胞（中位数 5.75；范围 2.12-33.4）。移植前总体缓解率为 91%（CI 84%至 98%），包括 70%（CRs 95%CI 59%至 81%）。60 名患者接受了移植，没有发生移植失败。移植后 49 名患者（82%CI 73%至 91%）达到完全缓解，6 名患者（10%CI 5%至 15%）达到部分缓解。在平均随访 27 个月后，30 个月时治疗失败的时间为 74%（95%CI 68%至 80%），无进展生存期为 71%（95%CI 65%至 77%），总生存期为 91%（CI 84%至 98%）。
BRESHAP 看起来是一种安全有效的移植前诱导方案，不会影响移植，并可实现长期缓解和生存。
