Venetoclax-rituximab with or without bendamustine vs bendamustine-rituximab in relapsed/refractory follicular lymphoma

Pier Luigi Zinzani, Ian W. Flinn, Sam L.S. Yuen, Max S. Topp, Chiara Rusconi, Isabelle Fleury, Katell Le Dû, Christopher Arthur, Barbara Pro, Giuseppe Gritti, Michael Crump, Adam Petrich, Divya Samineni, Arijit Sinha, Elizabeth A. Punnoose, Edith Szafer-Glusman, Nathalie Spielewoy, Mehrdad Mobasher, Kathryn Humphrey, Martin KornackerWolfgang Hiddemann*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


This open-label phase 2 study (CONTRALTO) assessed the safety and efficacy of BCL-2 inhibitor venetoclax (VEN) plus rituximab (R), and VEN plus bendamustine (B) and R, vs B + R (BR) alone in relapsed/refractory (R/R) follicular lymphoma. Patients in the chemotherapy-free arm (arm A: VEN + R) received VEN 800 mg/d plus R 375 mg/m2 on days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 4, 6, 8, 10, and 12. After a safety run-in with VEN 600 mg, patients in the chemotherapy-containing cohort were randomized to either VEN + BR (arm B; VEN 800 mg/d for 1 year + 6 cycles of BR [B 90 mg/m2 on days 1 and 2 and R 375 mg/m2 on day 1]) or 6 cycles of BR (arm C). Overall, 163 patients were analyzed (9 in the safety run-in and 52, 51, and 51 in arms A, B, and C, respectively). Complete metabolic/complete response rates were 17% (arm A), 75% (arm B), and 69% (arm C). Of patients in arm B, only 61% received ≥90% of the planned B dose vs 96% of patients in arm C. More frequent hematologic toxicity resulted in more reduced dosing/treatment discontinuation in arm B vs arm C. Rates of grade 3/4 adverse events were 51.9%, 93.9%, and 60.0% in arms A, B, and C, respectively. VEN + BR led to increased toxicity and lower dose intensity of BR than in arm C, but efficacy was similar. Optimizing dose and schedule to maintain BR dose intensity may improve efficacy and tolerability of VEN + BR, while VEN + R data warrant further study. This study was registered at as #NCT02187861. Key Points: • Chemotherapy-free VEN + R had modest efficacy and acceptable toxicity in relapsed/refractory disease warranting further study. • VEN + BR led to increased toxicity; optimized chemotherapeutic dosing and/or combinations remain to be explored.

Original languageEnglish (US)
Pages (from-to)2628-2637
Number of pages10
Issue number23
StatePublished - Dec 3 2020

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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