Venetoclax, bendamustine, and rituximab in patients with relapsed or refractory NHL: a phase Ib dose-finding study.

Journal Article (Journal Article;Multicenter Study)

BACKGROUND: Venetoclax is a selective, potent inhibitor of the anti-apoptotic B-cell leukemia/lymphoma-2 protein approved for treatment of chronic lymphocytic leukemia. We conducted a dose-finding study of venetoclax in combination with bendamustine-rituximab (BR) in patients with relapsed/refractory non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: BR was given for six cycles at standard doses. Intermittent and continuous oral venetoclax administration was explored at 50-1200 mg daily doses. Co-primary objectives included safety, pharmacokinetics (PKs), maximum-tolerated dose (MTD), and recommended phase II dose (RP2D); secondary objective was preliminary efficacy. RESULTS: Sixty patients were enrolled: 32 with follicular lymphoma, 22 with diffuse large B-cell lymphoma, and 6 with marginal zone lymphoma. Nausea (70%), neutropenia (68%), diarrhea (55%), and thrombocytopenia (52%) were the most frequent adverse events (AEs). Most common grade 3/4 AEs were neutropenia (60%) and lymphopenia (38%). Serious AEs were reported in 24 patients; the most frequent were febrile neutropenia and disease progression (8% each). Five patients died from either disease progression (n = 4) or respiratory failure (n = 1). MTD was not reached; RP2D for venetoclax-BR combination was established as 800 mg daily continuously. Venetoclax PK exposure with and without BR was comparable. For all patients, overall response rate was 65%. Median duration of overall response, overall survival, and progression-free survival was 38.3 months [95% confidence interval (CI) 10.4-NR], not yet reached, and 10.7 months (95% CI 4.3-21.0), respectively. CONCLUSIONS: This study established the safety profile of venetoclax in combination with BR, and results demonstrated tolerability and preliminary efficacy of the combination. Additional follow-up is needed to better determine the future role of BR plus venetoclax in the treatment of relapsed/refractory B-cell NHL. TRIAL REGISTERED:, NCT01594229.

Full Text

Duke Authors

Cited Authors

  • de Vos, S; Swinnen, LJ; Wang, D; Reid, E; Fowler, N; Cordero, J; Dunbar, M; Enschede, SH; Nolan, C; Petrich, AM; Ross, JA; Salem, AH; Verdugo, M; Agarwal, S; Zhou, L; Kozloff, M; Nastoupil, LJ; Flowers, CR

Published Date

  • September 1, 2018

Published In

Volume / Issue

  • 29 / 9

Start / End Page

  • 1932 - 1938

PubMed ID

  • 30060083

Pubmed Central ID

  • PMC6158762

Electronic International Standard Serial Number (EISSN)

  • 1569-8041

Digital Object Identifier (DOI)

  • 10.1093/annonc/mdy256


  • eng

Conference Location

  • England