Long-Term Follow-Up Confirms Benefits of Bendamustine Plus Rituximab Over R-CHOP or R-CVP in Patients With NHLs

At the 2017 ASCO Annual Meeting, Ian Flinn, MD, from Tennessee Oncology in Nashville, shared 5-year follow-up data from the open-label, phase III, non-inferiority BRIGHT study, which initially found that treatment with front-line bendamustine and rituximab (BR) was non-inferior to the standard regimens of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone) in treatment-naïve patients with indolent non-Hodgkin lymphoma (NHL) or mantle cell lymphoma (MCL).

The long-term results confirmed that BR produced response rates similar to R-CHOP and R-CVP, but also found that BR significantly improved progression-free survival (PFS), event-free survival (EFS), and duration of response (DOR).

“The field has come to a consensus that R-CHOP is not a very good therapy for patients with MCL,” Dr. Flinn told ASH Clinical News. “Many times, R-CHOP is used in older patients who are not going on to transplant, but I’m not so sure it’s also a good regimen for younger patients, even if they are going on to transplant.”

The BRIGHT trial included adult patients who had histologically verified CD20-positive B-cell lymphomas, adequate hematologic function, an Eastern Cooperative Oncology Group score of ≤2, and adequate renal function. Patients were excluded if they had chronic lymphocytic leukemia, small lymphocytic lymphoma, or grade 3 follicular lymphoma; central nervous system involvement; received prior radiation for NHL; or had an active malignancy other than NHL in the past 3 years (except for localized prostate cancer treated with hormone therapy, cervical carcinoma in situ, breast cancer in situ, or non-melanoma skin cancer following definitive treatment).

A total of 447 patients (median age = 60 years; range = 25-86 years) were randomized to receive six to eight cycles of either:

  • BR: bendamustine 90 mg/m2 administered intravenously (IV) on days 1 and 2 and rituximab 375 mg/m2 IV on day 1 (n=224);
  • R-CHOP: rituximab 375 mg/m2 IV on day 1; vincristine 1.4 mg/m2 (up to maximum dose of 2 mg/m2) IV on day 1; doxorubicin 50 mg/m2 IV on day 1; cyclophosphamide 750 mg/m2 IV on day 1; and prednisone 100 mg administered orally on days 1-5 (n=104); or
  • R-CVP: rituximab 375 mg/m2 IV on day 1; cyclophosphamide 750 mg/m2 or 1,000 mg/m2 IV on day 1; vincristine 1.4 mg/m2 (up to a maximum dose of 2 mg/m2) IV on day 1; and prednisone 100 mg administered orally on days 1-5 (n=119).

Eighty-three percent of patients in each group (BR and R-CHOP/R-CVP) had indolent NHL, and 16 percent and 17 percent, respectively, had MCL.

After a median duration of follow-up of 65.0 months for those treated with BR and 64.1 months for those treated with R-CHOP/R-CVP, 419 patients had evaluable follow-up data.

The 5-year PFS rates were significantly higher in patients treated with BR, compared with R-CHOP/R-CVP: 65.5 percent (95% CI 58.5-71.6) versus 55.8 percent (95% CI 48.4-62.5; hazard ratio [HR] = 0.61 [95% CI 0.45-0.85]; p=0.0025).

Durations of response were longer in the BR-treated group, compared with the R-CHOP/R-CVP groups (HR=0.66; 95% CI 0.47-0.92; p=0.0134), and rates of 5-year EFS were also greater in the BR group (HR=0.63; 95% CI 0.46-0.84; p=0.002). However, rates of 5-year overall survival were higher in the R-CHOP/R-CVP groups (81.7% vs. 85%; HR=1.15; 95% CI 0.72-1.84; p=0.5461), though this association was not statistically significant.

Notably, rates of survival with BR were similar across disease types, and Dr. Flinn noted that “this regimen is a good choice for patients as frontline therapy for these diseases – particularly patients with MCL.” In the indolent NHL cohort, HR for PFS with BR was 0.70 (95% CI 0.49-1.01; p=0.0582), but was 0.40 (95% CI 0.21-0.75; p=0.0035) in the MCL cohort.

Similar rates of rituximab maintenance were observed: 43 percent in the BR cohort and 45 percent in the R-CHOP/R-CVP cohort. Of the 75 patients who originally received R-CHOP or R-CVP and required second-line treatment, 36 percent (n=27) received bendamustine.

The overall adverse event (AE) profile was similar between both groups, Dr. Flinn and co-authors noted. Nausea was the most common AE, and the incidences of grade 3/4 non-hematologic AEs were not statistically different among the groups. “There was an increased risk of second malignancy in patients who received BR, which was unexpected,” he added. However, many of these malignancies were skin cancer. “There was still a numerical increase in patients who received BR versus R-CHOP or R-CVP, but the gap was much narrower and non-statistically significant [when excluding these cases],” Dr. Flinn said.

“People should have confidence that BR is a good and durable option,” Dr. Flinn said, “but it’s going to have a different set of side effects, which you need to discuss with your patients in order to choose which is the best approach.” In addition, the study design, in which investigators selected the treatment regimen they considered most appropriate for each patient, may have introduced selection bias – a potential study limitation.


Flinn I, van der Jagt R, Chang JE, et al. First-line treatment of iNHL or MCL patients with BR or R-CHOP/R-CVP: Results of the BRIGHT 5-year follow-up study. Abstract #7501. Presented at the 2017 American Society of Clinical Oncology Annual Meeting, June 3, 2017; Chicago, Illinois.