The combination of bendamustine plus rituximab proved to be noninferior to standard first-line chemotherapy in patients with previously untreated, advanced, indolent non-Hodgkin lymphoma (NHL) and mantle-cell lymphoma (MCL) in the phase 3 BRIGHT clinical trial.
The BRIGHT trial randomized 447 patients to bendamustine plus rituximab or to rituximab plus the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or rituximab plus the combination of cyclophosphamide, vincristine, and prednisone (R-CVP; physician’s choice).
Complete response (CR) was the primary end point, which showed no difference between bendamustine plus rituximab and standard chemotherapy, reported Ian Flinn, MD, MPH, Director of Hematologic Malignancies Research at the Sarah Cannon Research Institute, Nashville, TN.
In the absence of a single standard therapy for indolent NHL or MCL, the BRIGHT trial evaluated bendamustine plus rituximab, a regimen that is becoming standard in Germany, versus standard chemotherapy. The StiL NHL study, which was first reported on at the 2009 ASH annual meeting, showed a large difference in progression-free survival (PFS) in patients with follicular, indolent NHL and MCL, favoring bendamustine plus rituximab over R-CHOP.
In the current study, CR rates were 31% with bendamustine plus rituximab and 25% with standard chemotherapy. The CR ratio of 1.26 met the definition of noninferiority, Dr Flinn reported. It was not, however, statistically significant for the superiority of bendamustine plus rituximab over standard chemotherapy.
The overall response rates were 97% for bendamustine plus rituximab versus 91% for R-CHOP/R-CVP.
“The overall response rate was high in both treatment groups. Bendamustine plus rituximab is an important treatment option for previously untreated indolent NHL and MCL,” said Dr Flinn.
Although PFS is a more clinically meaningful end point than CR, the study was designed for a US Food and Drug Administration application and is a supportive trial for existing data that have longer end points, Dr Flinn explained.
“PFS is probably a better end point,” he acknowledged. Longer follow-up is needed to show PFS differences between the 2 arms, he noted.
Different Toxicity Profiles
The toxicity profiles of the 2 arms did, however, differ. Adverse events (AEs) of all grades included a higher incidence of nausea and vomiting, pyrexia, chills, drug hypersensitivity reactions, decreased appetite, rash, and pruritus for the bendamustine plus rituximab arm, and a higher incidence of constipation, paresthesia, peripheral neuropathy, and alopecia for the chemotherapy arms. With bendamustine plus rituximab, there were more ≥grade 3 hypersensitivity reactions, opportunistic infections, and respiratory and thoracic disorders. More frequent febrile neutropenia and alopecia were seen in the chemotherapy arms.
Despite the use of growth factor support, patients treated with R-CHOP had a higher incidence of ≥grade 3 hematologic AEs, including neutropenia and lymphopenia.
“There was a much greater use of growth factors in the R-CHOP arm, so lack of growth factor support could not explain the increased neutropenia observed with R-CHOP,” Dr Flinn noted. He said that the investigators expected less nausea and vomiting with the bendamustine plus rituximab combination, but they did not see that.
Bendamustine plus rituximab and R-CHOP and R-CVP have distinct toxicity profiles, which should be considered in treatment selection, he said.
A substudy of BRIGHT evaluated quality of life via patient-reported responses to 30 questions. Patients were surveyed at baseline and during intervals throughout treatment up to cycle 6. The study found that patients treated with bendamustine plus ri-tuximab had improved global health status, physical function, social and emotional function, fatigue, dyspnea, and constipation compared with the R-CHOP arm.Patients with Poor Performance Status
Martin Dreyling, MD, Professor at the University of Munich in Germany, commented that the lack of a difference in PFS favoring bendamustine plus rituximab was surprising, based on the previous findings of substantial benefit in the StiL NHL trial.
Dr Dreyling noted that bendamustine plus rituximab is better tolerated and noninferior to R-CHOP and, therefore, should be a good alternative for elderly patients and other patients with poor performance status. He said that he would not, however, consider this regimen to be the new standard of care, but an additional standard option.