Bendamustine Regimen More Effective, Better Tolerated Than Standard R-CHOP in Lymphoma

Long-term results of the German StiL NHL1 trial conducted in patients with indolent and mantle cell lymphomas show that first-line treatment with bendamustine plus rituximab (B-R) more than doubled progressionfree survival (PFS) compared with standard cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (R-CHOP). B-R also produced less toxicity (Abstract 3).

Mathias J. Rummel, MD, PhD, of Universitaetsklinik, Germany, presented the updated results of the multicenter phase III trial during Sunday’s Plenary Session. “I think we can conclude certainly that B-R is established as a front-line regimen for patients with indolent B-cell and nontransplant-eligible mantle cell lymphoma,” Discussant Michael E. Williams, MD, of the University of Virginia Medical Center, said. “It is to be expected that this will become a preferred and commonly used front-line regimen for these diseases.”

Bendamustine was originally developed about 50 years ago in former East Germany, but it only became available in the United States in 2008 and the European Union in 2010. Some oncologists currently use B-R, but R-CHOP remains the established regimen of choice in the United States and much of Europe.

The investigators recruited patients with previously untreated, CD20- positive, indolent non-Hodgkin or mantle cell lymphomas. Their initial intent was to demonstrate that B-R was noninferior to R-CHOP for PFS at 3 years and also less toxic. The data readily showed this and also established B-R as superior to R-CHOP.

After following 514 evaluable patients for a median of 45 months, median PFS was 69.5 months in the B-R group compared with 31.2 months in the R-CHOP group (p = 0.0000148; Figure). B-R was not only superior in the overall patient population, but was also more effective than R-CHOP in exploratory analyses in the subgroups with follicular lymphoma, mantle cell lymphoma, and Waldenström macroglobulinemia. The investigators did not fi nd a signifi cant improvement with B-R in marginal zone lymphoma.

No difference in overall survival between the two groups has emerged thus far. Dr. Rummel commented that this is not surprising given the protracted nature of indolent lymphomas and potential confounding caused by use of a variety of salvage therapies among the patients with progressive disease.

Complementing its effi cacy profile, B-R also showed a more favorable tolerability profi le compared with R-CHOP. Severe neutropenia was markedly decreased with B-R (29% vs. 69% with RCHOP), although Dr. Rummel pointed out a higher incidence of severe lymphocytopenia with B-R versus R-CHOP (74% vs. 43%).

The B-R group also showed a higher incidence of all-grade skin reactions compared with R-CHOP (40% vs. 15%; p = 0.0003); however, the bendamustine regimen resulted in a significantly lower incidence of paresthesias (p < 0.0001), stomatitis (p < 0.0001), and infections (p = 0.0025).

Dr. Rummel also emphasized the alopecia results—a side effect particularly important to patients. “It is well known that with R-CHOP patients have hair loss, but with B-R not a single patient has any hair loss,” he said.

To allay another potential concern, Dr. Rummel noted that there has been no increase in secondary malignancies with B-R observed to date based on nearly 4 years of follow-up.