A 3-Arm Randomized Phase II Study of Bendamustine/Rituximab with Bortezomib Induction or Lenalidomide Continuation in Untreated Follicular Lymphoma: ECOG-ACRIN E2408. Clinical cancer research : an official journal of the American Association for Cancer Research Evens, A. M., Hong, F., Habermann, T. M., Advani, R. H., Gascoyne, R. D., Witzig, T. E., Quon, A., Ranheim, E. A., Ansell, S. M., Cheema, P. S., Dy, P. A., O'Brien, T. E., Winter, J. N., Cescon, T. P., Chang, J. E., Kahl, B. 2020


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 (NCT01332968).RESULTS: For induction, 92%, 87%, and 86% of patients randomized to BR-R, BVR-R, or BR-LR received 6 cycles, respectively. CR rate with BR vs. BVR induction was 62% vs. 75% (P=0.04). One-year DFS rates with BR-R vs. BR-LR were 85% vs. 67%, respectively (P=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 vs. BR were neutropenia and sensory neuropathy (12% vs. <1%); 83% of the latter with intravenous bortezomib. The most common grade 3-4 AEs related to LR vs. rituximab maintenance were neutropenia 66% vs. 21% (P<0.0001) and febrile neutropenia 10% vs. 2% (P=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=0.36) with OS rates of 87%, 90%, and 84%, respectively (P=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 are recommended in untreated FL.

View details for DOI 10.1158/1078-0432.CCR-20-1345

View details for PubMedID 32532790