The latest data from the three-arm randomized phase 2 ECOG-ACRIN E2408 trial, which sought to improve upon frontline bendamustine/rituximab (BR) induction therapy followed by rituximab maintenance in untreated high-risk follicular lymphoma (FL), have yielded disappointing results: neither adding bortezomib to BR induction nor adding lenalidomide following BR induction improves outcomes.
For the trial, 289 patients were randomized to receive either BR induction followed by two-year rituximab maintenance (BR-R), BR with bortezomib followed by rituximab maintenance (BVR-R), or BR followed by one year of lenalidomide with rituximab maintenance (BR-LR) for co-primary end points of complete remission and one-year disease-free survival.
All six cycles of induction therapy were completed by 92% of patients in the BR-R arm, 87% of patients in the BVR-R arm, and 86% of patients in the BR-LR arm. The complete response rate was higher for BVR induction therapy compared with BR induction therapy (75% vs 62%, with a P value of 0.04). Compared with BR-R, BR-LR resulted in a lower one-year disease-free survival rate (67% vs 85%, P=0.0009). With a median follow-up of five years, there was no statistically significant difference in three-year progression-free survival rates between the three regimens (77% for BR-R, 82% for BVR-R, and 76% for BR-LR, P=0.36). Differences in overall survival, with rates of 87%, 90%, and 84%, respectively, were also not statistically significant (P=0.79).
The lower disease-free survival rate with BR-LR versus BR-R "was due to an imbalance in complete response rates post-BR induction and discontinuation due to adverse events," write the investigators in their publication in Clinical Cancer Research, led by first author Andrew M. Evens, DO, MSc, Associate Director for Clinical Services and Director of the Lymphoma Program at the Rutgers Cancer Institute of New Jersey in New Brunswick, New Jersey.
The most frequent grade 3/4 adverse events that were higher with BVR versus BR were neutropenia and sensory neuropathy (12% vs <1%). Most of the sensory neuropathy (83%) occurred with intravenous bortezomib. The most frequent grade 3/4 adverse events that were higher with lenalidomide/rituximab versus rituximab maintenance were neutropenia (66% vs 21%, P<0.0001) and febrile neutropenia (10% vs 2%, P=0.05). Overall, treatment-related mortality occurred in 1.4% of patients.
"Altogether, neither bortezomib added to BR induction nor lenalidomide added to rituximab maintenance immediately post-BR induction is recommended in untreated FL," conclude Dr. Evens and colleagues.
For More Information
Evens AM, Hong F, Habermann TM, et al (2020). A three-arm randomized phase II study of bendamustine/rituximab with bortezomib induction or lenalidomide continuation in untreated follicular lymphoma: ECOG-ACRIN E2408. Clin Cancer Res. [Epub ahead of print] DOI:10.1158/1078-0432.CCR-20-1345
Image credit: Ed Uthman. Licensed under CC BY 2.0