Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study

Abstract

This randomized, noninferiority (NI), global, phase 3 study evaluated the efficacy and safety of bendamustine plus rituximab (BR) vs a standard rituximab-chemotherapy regimen (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP] or rituximab plus cyclophosphamide, vincristine, and prednisone [R-CVP]) for treatment-naive patients with indolent non-Hodgkin's lymphoma or mantle cell lymphoma. Investigators preassigned the standard treatment regimen they considered most appropriate for each patient; patients were randomized to receive BR (n = 224) or standard therapy (R-CHOP/R-CVP, n = 223) for 6 cycles; 2 additional cycles were permitted at investigator discretion. Response was assessed by a blinded independent review committee. BR was noninferior to R-CHOP/R-CVP, as assessed by the primary end point of complete response rate (31% vs 25%, respectively; P = .0225 for NI [0.88 margin]). The overall response rates for BR and R-CHOP/R-CVP were 97% and 91%, respectively (P = .0102). Incidences of vomiting and drug-hypersensitivity reactions were significantly higher in patients treated with BR (P < .05), and incidences of peripheral neuropathy/paresthesia and alopecia were significantly higher in patients treated with standard-therapy regimens (P < .05). These data indicate BR is noninferior to standard therapy with regard to clinical response with an acceptable safety profile. This trial was registered at www.clinicaltrials.gov as #NCT00877006.

Figures

Figure 1

Study design. *Up to 8 cycles at investigator discretion; B, bendamustine; C, cyclophosphamide; D, doxorubicin; P, prednisone; R, rituximab; V, vincristine.

Figure 2

Patient disposition in the BRIGHT study. *Efficacy-evaluable population of all treated patients who have a baseline and ≥1 postbaseline efficacy evaluation, or who discontinued due to progressive disease (PD) and did not have major protocol violations.

Figure 3

CR-rate ratios with 95% CIs. CR-rate ratio and P value for a Sup test are calculated using the Cochran–Mantel–Haenszel test stratified by predetermined standard treatment and lymphoma type (mantle cell vs other types). P value is calculated based on weighted z statistics for an NI test of CR-rate ratio (BR vs R-CHOP/R-CVP) of 0.88. (Top) BR compared with combined R-CHOP/R-CVP group. (Bottom) Analysis by preassigned treatment group. *CR-rate ratio and P value for a Sup test are calculated using the Cochran–Mantel–Haenszel test stratified by predetermined standard treatment and lymphoma type (mantle cell vs other types). †P value is calculated based on weighted z statistics for an NI test of CR-rate ratio (BR vs R-CHOP/R-CVP) of 0.88.