Updated results of the StiL NHL1 study, presented at the 2012 ASCO Annual Meeting Plenary Session, showed that bendamustine plus rituximab (Rituxan) more than doubled the median progression-free survival, compared with the standard R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). No difference in overall survival was observed.
Developed in East Germany
“We saw a huge difference favoring bendamustine/rituximab over R-CHOP…. Bendamustine/rituximab is not only less toxic, but also more effective than the most-often-used first-line approach, and should be considered a preferred first-line treatment for these patients,” said lead investigator Mathias J. Rummel, MD, PhD, of the University Hospital in Giessen, Germany.
Explaining the rationale for the simpler regimen, he said at a press briefing, “R-CHOP, which contains five different drugs, has been standard treatment in most Western countries. It has an absolute place in diffuse large B-cell lymphoma, but there has been ongoing debate as to whether we need such an aggressive regimen in indolent lymphoma.”
Bendamustine is approved in the United States for chronic lymphocytic leukemia and for second-line rituximab-refractory NHL.
StiL NHL1 Details
The multicenter German study enrolled 549 patients newly diagnosed with stage III or IV indolent NHL (follicular, Waldenstrom’s macroglobulinemia, marginal zone, small lymphocytic, or mantle cell) and randomly assigned to standard treatment with R-CHOP (rituximab at 375 mg/m2, cyclophosphamide at 750 mg/m2, doxorubicin at 50 mg/m2, vincristine at 1.4 mg/m2 [maximum dose, 2 mg], prednisone at 100 mg) or bendamustine at 90 mg/m2 on days 1-2 plus rituximab at 375 mg/m2.
After a median follow-up of 45 months, median progression-free survival more than doubled with the bendamustine/rituximab regimen: 69.5 months vs 31.2 months with R-CHOP, a highly significant 42% reduction in the risk of progression (P = .0000148), Dr. Rummel reported.
The significant progression-free survival benefit observed with bendamustine/rituximab extended to all risk groups irrespective of age and Follicular Lymphoma International Prognostic Index (FLIPI) score. All histologic subtypes benefited except for marginal zone lymphoma, where progression-free survival was comparable. The biggest advantage was observed in patients with Waldenstrom’s macroglobulinemia (69.5 vs 28.1 months; P = .0033).
Bendamustine/rituximab also produced a significantly higher complete response rate (39.8%) than R-CHOP (30.0%), although overall response rates were similar—approximately 92% per arm. Overall survival was also similar: 80.1% at 5 years with bendamustine/rituximab and 77.8% with R-CHOP.
“So far, we have not observed differences in overall survival,” he said. “This is not surprising, since indolent lymphoma may need a longer observation period.” Subjects were also allowed to cross over upon disease progression. More patients received salvage treatment with bendamustine/rituximab than with R-CHOP, and more received transplants after R-CHOP. “Imbalances in salvage therapy may influence survival,” he suggested.
High Tolerability Observed
As predicted for the simpler regimen, bendamustine/rituximab was associated with less toxicity. Only skin rash was more frequent with bendamustine/rituximab, mainly erythema and allergic reaction (all grades, 31% vs 15%), which were not dose-limiting. Grade 3/4 hematologic toxicity was significantly worse with R-CHOP, including neutropenia (69% vs 29%) and leukocytopenia (72% vs 37%). Alopecia was essentially universal with R-CHOP but completely lacking with bendamustine/rituximab; infectious complications, neuropathy, and need for growth factors were also significantly less frequent with bendamustine/rituximab.
Second malignancies were observed in 20 patients on bendamustine/rituximab and 23 on R-CHOP, and transformation to aggressive disease occurred in about 2% of the total group. ■
Disclosure: Dr. Rummel disclosed honoraria and research funding from Mundipharma and Roche.
1. Rummel MR, Niederle N, Maschmeyer G, et al: Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment in patients with indolent and mantle cell lymphomas: Updated results from the StiL NHL1 study. 2012 ASCO Annual Meeting. Abstract 3. Presented June 3, 2012.
Richard I. Fisher, MD, the Samuel E. Durand Professor of Medicine at the University of Rochester Medical Center in Rochester, New York, cautioned that it is too early to embrace the bendamustine/rituximab regimen.
“Bendamustine is a very active agent with moderate toxicity that...
Michael Williams, MD, the Byrd S. Leavell Professor of Medicine and Chief of Hematologic Malignancies at the University of Virginia Cancer Center, Charlottesville, commented, “Bendamustine/rituximab provides equivalent or better responses vs R-CHOP [rituximab, cyclophosphamide, doxorubicin,...