Research in context
Evidence before this study
So far, no randomised trials have compared the efficacy of one chemoimmunotherapy with another in patients with relapsed indolent and mantle-cell lymphoma. Treatment decisions for these patients are therefore challenging. Given that patients are typically elderly with comorbidities, effective treatment options that are well tolerated are needed for these patients. The combination of bendamustine and rituximab has been effective and well tolerated in previous phase 2 studies in patients relapsing after alkylator-containing chemotherapy.
Added value of this study
In this randomised, multicentre, phase 3 trial, progression-free survival for patients with relapsed indolent non-Hodgkin lymphoma and mantle-cell lymphoma who received bendamustine plus rituximab was non-inferior to—and indeed superior to—that with fludarabine plus rituximab. Overall survival was also longer with bendamustine plus rituximab than with fludarabine plus rituximab. No differences were reported in safety outcomes between treatment groups. A subset of patients receiving rituximab maintenance had longer overall survival than patients not receiving rituximab maintenance. Our study is the first to show a survival benefit of one chemoimmunotherapy compared with another, and suggests that the use of rituximab maintenance potentially further improves outcomes in patients who relapsed.
Implications of all the available evidence
Results of our study suggest that preference be given to bendamustine plus rituximab over fludarabine plus rituximab for treatment of relapsed indolent and mantle-cell lymphomas, as shown by the significant improvement in progression-free and overall survival. The combination of bendamustine and rituximab is effective and well tolerated and should be regarded as a key treatment option for these patients. Results of ongoing studies combining bendamustine plus rituximab as a backbone therapy with newer drugs—such as inhibitors of BTK (eg, ibrutinib), PI3K (eg, idelalisib), and Bcl-2 (eg, venetoclax)—will help to establish the role of novel combinations in this setting.