A three-arm randomized Phase II study of bendamustine/rituximab with bortezomib induction or lenalidomide continuation in untreated follicular lymphoma: ECOG-ACRIN E2408

Andrew M. Evens*, Fangxin Hong, Thomas M. Habermann, Ranjana H. Advani, Randy D. Gascoyne, Thomas E. Witzig, Andrew Quon, Erik A. Ranheim, Stephen M. Ansell, Puneet Singh Cheema, Philip A. Dy, Timothy E. O'Brien, Jane N. Winter, Terrence P. Cescon, Julie E. Chang, Brad S. Kahl

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Purpose: We sought to improve upon frontline bendamustine/ rituximab (BR) induction therapy followed by rituximab maintenance in untreated high-risk follicular lymphoma (FL). Patients and Methods: Patients were randomized to BR induction followed by 2-year rituximab maintenance (BR-R), BR with bortezomib and rituximab maintenance (BVR-R), or BR followed by lenalidomide (1 year) with rituximab maintenance (BR-LR). Dual primary objectives were complete remission (CR) rate and 1-year disease-free survival (DFS); 289 patients enrolled (NCT01216683). Results: For induction, 92%, 87%, and 86% of patients randomized to BR-R, BVR-R, or BR-LR received six cycles, respectively. CR rate with BR versus BVR induction was 62% versus 75%, respectively (P ¼ 0.04). One-year DFS rates with BR-R versus BR-LR were 85% versus 67%, respectively (P ¼ 0.0009). This was due to an imbalance in CR rates post-BR induction and discontinuation due to adverse events (AEs). The most common grade 3-4 AEs for BVR versus BR were neutropenia and sensory neuropathy (12% vs <1%); 83% of the latter occurred with intravenous bortezomib. The most common grade 3-4 AEs related to LR versus rituximab maintenance were neutropenia 66% versus 21%, respectively (P < 0.0001), and febrile neutropenia 10% versus 2%, respectively (P ¼ 0.05). The overall treatment-related mortality was 1.4%. With 5-year median follow-up, 3-year PFS rates for BR-R, BVR-R, and BR-LR were 77%, 82%, and 76%, respectively (P ¼ 0.36) with OS rates of 87%, 90%, and 84%, respectively (P ¼ 0.79). For prognostication, CR rate and POD-24 were associated with survival. Conclusions: Altogether, neither bortezomib added to BR induction nor lenalidomide added to rituximab maintenance immediately post-BR induction is recommended in untreated FL.

Original languageEnglish (US)
Pages (from-to)4468-4477
Number of pages10
JournalClinical Cancer Research
Volume26
Issue number17
DOIs
StatePublished - Sep 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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