Bendamustine Plus Rituximab Maintains Frontline PFS Benefit in MCL, iNHL After 5 Years

Ian W. Flinn, MD, PhD

Five-year follow-up from the BRIGHT study confirmed that bendamustine plus rituximab (BR) is associated with improved progression-free survival (PFS) compared with R-CHOP or R-CVP in patients with mantle cell lymphoma (MCL) or indolent non-Hodgkin lymphoma (iNHL).

Lead author Ian W. Flinn, MD, PhD, director, Blood Cancer Research Program, principal investigator, Sarah Cannon Research Institute, presented the results during the 2017 ASCO Annual Meeting. He said these updated findings show that BR confers a benefit for PFS, event-free survival (EFS), and duration of response (DOR). Compared with R-CHOP/R-CVP, the hazard ratio (HR) for PFS for patients assigned to BR was 0.61 (95% CI, 0.45-0.85; P = .0025), the HR for EFS was 0.63 (95% CI, 0.46-0.84; P = .0020), and the HR for overall survival (OS) was 1.15 (95% CI, 0.72-1.84; P = .5461).

Specifically comparing BR to the R-CHOP subgroup, the HR for PFS was 0.65 (P = .08). The HR for PFS with BR versus R-CVP was 0.59 (P = .0128). For the subgroup of patients with MCL, the HR for PFS was 0.4 (P = .0035) with BR versus R-CHOP/R-CVP, and the HR for the same comparison was 0.7 (P = .0582) for patients with iNHL.

“The progression-free survival, event-free survival, and duration of response were significantly in favor of the combination of bendamustine and rituximab versus the R-CHOP or R-CVP regimen,” Flinn said. “There appeared to be a greater benefit of BR versus R-CVP, and the strongest benefit was in the mantle cell lymphoma subgroup.”

The 5-year PFS rate for BR was 65.5% (95% CI, 58.5-71.6) versus 55.8% (95% CI, 48.4-62.5) for R-CHOP/R-CVP. However, overall survival (OS) was not significantly better for patients assigned to BR. The 5-year OS rate was 81.60% (95% CI,75.7-86.3) with BR compared with 85% (95% CI, 79.2-89.2) with R-CHOP/R-CVP.

In BRIGHT, a phase III, open-label, noninferiority study, 447 patients with MCL or iNHL were randomly assigned to 6 to 8 cycles of therapy with BR or R-CHOP/R-CVP. A total of 419 patients were available for follow-up; 224 in the BR group, 104 in the R-CHOP group, and 119 in the R-CVP group.

About 40% of patients in both groups received rituximab maintenance therapy. Flinn said 22% of patients assigned to BR underwent second-line treatment compared with 34% of patients assigned to R-CHOP/R-CVP.

DOR was also superior for patients assigned to BR, at 65.5% versus 56.9% (HR, 0.66; 95% CI, 0.47-0.92; P = .0134). As with PFS, patients with MCL had better outcomes compared with iNHL. In MCL, 5-year DOR was 39.7% versus 15.9% with R-CHOP/R-CVP (HR, 0.47; 95% CI, 0.24-0.91; P = .0231). In iNHL, 5-year DOR was 70.5% versus 62.4% with R-CHOP/R-CVP (HR, 0.73; 95% CI, 0.50-1.07; P = .1051).

Forty patients in the BR arm died on-study compared with 32 for R-CHOP/R-CVP. Most patients, 16 in the BR arm and 17 in the R-CHOP/R-CVP arm, died due to disease progression. More patients in the BR arm died from cardiovascular causes (7 vs 2), infection (6 vs 3), and secondary malignancy (5 vs 3).

Patients assigned to BR also experienced more secondary malignancies, 42 versus 24 (P = .022). That was true even when investigators excluded NHL and non-melanoma skin cancers: 22 versus 13 (P = .133), though Flinn said the difference was not statistically significant.

Patients in the BR group were more likely to experience squamous cell carcinoma (12 vs 2) and basal cell carcinoma (9 vs 4), as well as other solid tumors (19 vs 11).

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. J Clin Oncol 35, 2017 (suppl; abstr 7500).