Bendamustine and rituximab for the treatment of relapsed indolent and mantle cell lymphoma: when timing of a study matters

In a recent issue of The Lancet Oncology, Rummel and colleagues reported the mature results of StiL NHL 2-2003, a multicenter, randomized, open-label, non-inferiority phase 3 trial comparing bendamustine plus rituximab (BR) with fludarabine plus rituximab (FR) in patients with relapsed or refractory (R/R) indolent non-Hodgkin lymphoma (iNHL) or mantle-cell lymphoma (MCL) (1). When this study was conceived, fludarabine-containing regimens were widely used, and rituximab was rapidly being integrated into the chemotherapy regimens for CD20-positive lymphomas (Table 1) (12). This study and others reintroduced bendamustine for the treatment of lymphoid neoplasms after its long clinical abeyance. In fact, the authors reported the results of a simultaneous trial, the StiL NHL 1-2003, demonstrating the superiority of BR as compared to rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone (R-CHOP) in patients with newly diagnosed iNHL or MCL (13).