Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd #368, Houston, TX, 77030, USA.
University of Tennessee, Knoxville, TN, USA.
J Hematol Oncol. 2021 Oct 30;14(1):179. doi: 10.1186/s13045-021-01188-x.
Ibrutinib plus venetoclax, given with an ibrutinib lead-in, has shown encouraging clinical activity in early phase studies in mantle cell lymphoma (MCL). The ongoing phase 3 SYMPATICO study evaluates the safety and efficacy of concurrently administered, once-daily, all-oral ibrutinib plus venetoclax in patients with relapsed/refractory MCL. A safety run-in (SRI) cohort was conducted to inform whether an ibrutinib lead-in should be implemented for the randomized portion. Patients received concurrent ibrutinib 560 mg continuously plus venetoclax in a 5-week ramp-up to venetoclax 400 mg for up to 2 years. The primary endpoint was occurrence of tumor lysis syndrome (TLS) and dose-limiting toxicities (DLTs). The SRI cohort enrolled 21 patients; six and 15 were in low- or increased-risk categories for TLS, respectively. During the 5-week venetoclax ramp-up, three patients had DLTs, and one patient at increased risk for TLS had a laboratory TLS; no additional TLS events occurred during follow-up. With a median follow-up of 31 months, the overall response rate was 81% (17/21); 62% (13/21) of patients had a complete response. SRI data informed that the randomized portion should proceed with concurrent ibrutinib plus venetoclax, with no ibrutinib lead-in. Ibrutinib plus venetoclax demonstrated promising efficacy; no new safety signals were observed.Trial registration: ClinicalTrials.gov, NCT03112174. Registered 13 April 2017, https://clinicaltrials.gov/ct2/show/NCT03112174 .
伊布替尼联合维奈托克，在套细胞淋巴瘤（MCL）的早期研究中表现出令人鼓舞的临床活性。正在进行的 3 期 SYMPATICO 研究评估了复发/难治性 MCL 患者同时接受每日一次、全口服伊布替尼联合维奈托克治疗的安全性和有效性。进行了安全性预试验（SRI）队列，以确定是否应在随机部分实施伊布替尼导入。患者接受伊布替尼 560mg 持续联合维奈托克治疗，5 周逐渐加量至维奈托克 400mg，持续 2 年。主要终点是肿瘤溶解综合征（TLS）和剂量限制毒性（DLT）的发生。SRI 队列入组 21 例患者；分别有 6 例和 15 例患者具有低风险或高风险 TLS。在维奈托克爬坡期间，3 例患者发生 DLT，1 例高风险 TLS 患者发生实验室 TLS；随访期间未发生其他 TLS 事件。中位随访 31 个月，总缓解率为 81%（21/21）；62%（21/21）的患者达到完全缓解。SRI 数据表明，应在无伊布替尼导入的情况下继续进行随机部分伊布替尼联合维奈托克治疗。伊布替尼联合维奈托克显示出良好的疗效；未观察到新的安全性信号。试验注册：ClinicalTrials.gov，NCT03112174。于 2017 年 4 月 13 日注册，https://clinicaltrials.gov/ct2/show/NCT03112174。
