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

  

Authors:	Grieve, C.; Joseph, A.; Drullinsky, P.; Zelenetz, A. D.; Hamlin, P.; Kumar, A.
Article Title:	Phase I study of bendamustine, rituximab, ibrutinib, and venetoclax in relapsed, refractory mantle cell lymphoma
Abstract:	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. © 2023 Informa UK Limited, trading as Taylor & Francis Group.
Keywords:	adult; clinical article; aged; constipation; fatigue; neutropenia; cancer recurrence; diarrhea; drug dose reduction; drug safety; rituximab; edema; progression free survival; mantle cell lymphoma; multiple cycle treatment; nausea; thrombocytopenia; bendamustine; dizziness; rash; gastrointestinal toxicity; therapy delay; maximum tolerated dose; phase 1 clinical trial; tumor cell destruction; overall response rate; refractory cancer; lymphoma and hodgkin disease; chemotherapeutic approaches; ibrutinib; intention to treat analysis; human; male; female; article; immunotherapeutic approaches; venetoclax; ecog performance status; mantle cell lymphoma international prognostic index
Journal Title:	Leukemia and Lymphoma
Volume:	65
Issue:	2
ISSN:	1042-8194
Publisher:	Taylor & Francis Group
Date Published:	2024-01-01
Start Page:	235
End Page:	241
Language:	English
DOI:	10.1080/10428194.2023.2283393
PROVIDER:	scopus
PUBMED:	38264906
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85177683185&doi=10.1080%2f10428194.2023.2283393&partnerID=40&md5=d662a542b9045b862f082f30bbe46c98
Notes:	Article -- Source: Scopus

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