Results from the BRIGHT study combined with long-term safety data from other studies suggest that bendamustine (Treanda) plus rituximab (Rituxan) “may be an important alternative treatment option” for the initial treatment of patients with low-grade non-Hodgkin lymphoma (NHL) and mantle cell lymphoma (MCL), researchers reported in Blood.
This randomized, noninferiority, phase III study evaluated the efficacy and safety of bendamustine plus rituximab vs a standard rituximab-chemotherapy regimen (R-CHOP [rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone] or R-CVP [rituximab plus cyclophosphamide, vincristine, and prednisone]) for treatment-naive patients with indolent NHL or MCL. Participating centers were located in the United States, Canada, Brazil, Peru, Mexico, Australia, and New Zealand. The lead author was Ian W. Flinn, MD, of the Sarah Cannon Research Institute in Nashville.
Eligible patients were at least 18 years old and had CD20-positive indolent NHL or MCL. “Patients were required to be treatment-naive with a need for treatment as indicated by the presence of ≥ 1 of the following: B symptoms, large tumor mass (characterized by lymph node with a diameter > 3 cm in 3 or more regions or by a lymph node with a diameter > 7 cm in 1 region), presence of lymphoma-related complications, or hyperviscosity syndrome attributed to monoclonal gammopathy,” the investigators explained.
“During screening, the investigators preassigned patients to the most appropriate standard treatment (R-CHOP/R-CVP) based on their performance status, comorbidities, and general health. After confirmation that patients met the eligibility criteria for the study, the preassigned patients were then randomized to open-label treatment with either [bendamustine/rituximab] or the standard therapy at a 1:1 ratio,” the authors wrote.
Six cycles were planned and two additional cycles were permitted at investigator discretion. Among those treated with standard therapy, 104 received R-CHOP and 119 got R-CVP.
Assessed by the primary endpoint of complete response rate, bendamustine/rituximab was noninferior to R-CHOP/R-CVP (31% vs 25%, P = .0225 for noninferiority). The complete response rate for bendamustine/rituximab was greater than the 22% threshold for noniferiority, ie, more than 88% of the complete response rate for standard therapy.
The higher complete response rate with bendamustine/rituximab therapy was not statistically superior to standard therapy (P = .1269), the researchers noted. “Overall response rates were 97% for the [bendamustine/rituximab] treatment group and 91% for the standard-therapy treatment group, which was statistically superior for the [bendamustine/rituximab] treatment group [complete response rate ratio = 1.04, 95% CI = 0.99-1.09, P = .0102].”
The safety profiles of the regimens differed. “Incidences of vomiting and drug-hypersensitivity reactions were significantly higher in patients treated with [bendamustine/rituximab] (P < .05), and incidences of peripheral neuropathy/paresthesia and alopecia were significantly higher in patients treated with standard-therapy regimens (P < .05),” the investigators reported.
By the data cutoff point in March 2012, 21 patients had died, 12 in the bendamustine/rituximab treatment group and 9 in the standard-therapy group. The deaths of three patients in the bendamustine/rituximab] treatment group “were possibly related to treatment (pneumonia, chronic obstructive pulmonary disease, and sepsis),” the authors wrote. “Follow-up is continuing for [progression-free and overall survival], and a new study will provide further data on long-term toxicities,” the researchers added.
This trial was registered at ClinicalTrials.gov as NCT00877006. ■
Flinn IW, et al: Blood. March 3, 2014 (early release online).