Phase I study of bendamustine, rituximab, ibrutinib, and venetoclax in relapsed, refractory mantle cell lymphoma

被引：1

作者：

Grieve, Clare ^{[1
]}

Joseph, Ashlee ^{[1
]}

Drullinsky, Pamela ^{[2
]}

Zelenetz, Andrew D. ^{[1
]}

Hamlin, Paul ^{[1
]}

Kumar, Anita ^{[1
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Med, Lymphoma Serv, 530 East 74th St, New York, NY 10021 USA

[2] Mem Sloan Kettering Canc Ctr, Dept Med, Breast Med Serv, New York, NY 10021 USA

来源：

LEUKEMIA & LYMPHOMA | 2024年 / 65卷 / 02期

关键词：

Chemotherapeutic approaches; lymphoma and Hodgkin disease; immunotherapeutic approaches; 1ST-LINE TREATMENT; MULTICENTER; INDOLENT; TRIAL;

D O I：

10.1080/10428194.2023.2283393

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

This dose-finding study evaluated safety of venetoclax plus Bendamustine-Rituximab-Ibrutinib in relapsed/refractory MCL. Six 28-day cycles were administered in a 3 + 3 dose-escalation design. Dose level 1 (DL1) included Bendamustine 90 mg/m2 on day 1-2, Rituximab 375 mg/m2 on day 1, and Ibrutinib 560 mg daily. Venetoclax was dosed with ramp-up and at 400 mg starting in Cycle 2 for 5 days. The most common adverse events were thrombocytopenia (80%), constipation (60%), and fatigue (60%). Rare hematologic grade 3-4 AEs, 1 dose-limiting toxicity at DL1 (prolonged grade 3 thrombocytopenia), and delayed hematologic toxicity were observed. DL-1 with Bendamustine dose-reduced to 70 mg/m2 (n = 3) revealed no significant toxicity. The overall and complete response rates were both 80% (8/10). This study underscored that venetoclax combined with chemoimmunotherapy is complicated by hematologic toxicity, limiting future development. Although a maximum tolerated dose was not formally established given early study closure, this study demonstrated preliminary tolerability and efficacy of Bendamustine-Rituximab-Ibrutinib-Venetoclax at DL-1.

引用

页码：235 / 241

页数：7

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