CHICAGO—The two-drug combination of bendamustine (Treanda) plus rituximab(Drug information on rituximab) (Rituxan) is more effective and less toxic than the standard CHOP regimen—cyclophosphamide (Cytoxan), doxorubicin(Drug information on doxorubicin) (Adriamycin), vincristine (Oncovin), and prednisone—plus rituximab and should be considered as “preferred first-line treatment for patients with follicular lymphoma, indolent lymphoma, and elderly patients with mantle cell lymphoma,” according to Mathias Rummel, MD, PhD, of University Hospital, Giessen, Germany.
He presented updated findings from the phase III, multicenter Study Group Indolent Lymphomas (StiL) NHL 1 study, results of which were first reported at the 2009 annual meeting of the American Society of Hematology.
Bendamustine, an intravenously administered alkylating agent, was first discovered 50 years ago in the former German Democratic Republic (East Germany). It was approved in 2008 by the US Food and Drug Administration for treatment of indolent B-cell non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia.
The combination of CHOP plus rituximab (R-CHOP) has been the traditional standard of care in the United States for follicular lymphoma, Waldenstrom's macroglobulinemia, and mantle cell lymphoma (MCL). That regimen, noted Dr. Rummel, is associated with a range of adverse effects, including cardiac, hematologic, and neurologic toxicity, as well as infectious complications. He acknowledged that CHOP has a role in treating diseases such as diffuse large B-cell lymphoma, but said "there was always a debate” as to whether such an aggressive regimen is warranted for treatment of patients with indolent lymphomas.
In the StiL NHL 1 trial, 549 patients with untreated indolent NHL or MCL were randomized to either of the two regimens. After a median follow-up of 45 months, investigators observed “a huge difference” in median progression-free survival among the 514 evaluable patients, said Rummel: 69.5 months in the bendamustine plus rituximab (B-R) group versus 31.2 months for the R-CHOP group. Overall survival did not differ between the two groups, partly because nearly half of the R-CHOP patients whose disease continued to progress were then permitted to receive B-R, and partly because survival for indolent lymphomas tends to be long, making progression-free survival the most reliable measure of clinical benefit and patient quality of life.
Although there was a higher incidence of mild skin reactions in the B-R group, there was no hair loss and a significantly lower incidence of neurotoxicity and infectious complications compared with the R-CHOP group (all at P < .0001). Moderate to severe declines in neutrophil counts occurred in 69% of the R-CHOP patients and 29% of the B-R group; G-CSF treatment was required after 20% percent of R-CHOP chemotherapy cycles versus 4% of B-R cycles.
Both drug combinations had similar overall rates of response (92.7% for B-R and 91.3% for R-CHOP) but the bendamustine combination had significantly more complete responses—40% vs 30% for the CHOP combination.
“B-R is established as a front-line regimen for indolent lymphomas,” commented Michael E. Williams, MD, chief of the hematologic malignancies section at the University of Virginia School of Medicine Cancer Center, Charlottesville. “It provides equivalent or better responses versus R-CHOP and less toxicity.” He said further studies are necessary to confirm the NHL 1 study findings and to determine appropriate patient selection and dosing.
"It's certainly remarkable to have an agent provide superior efficacy and decreased toxicity at the same time," commented Bruce Roth, MD, of Washington University School of Medicine in St. Louis.
The study was supported by Mundipharma and Roche Diagnostics.
1. Rummel MJ, Niederle N, Maschmeyer G, et al. Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent and mantle cell lymphomas (MCL): Updated results from the StiL NHL1 study. J Clin Oncol 2012;30:(suppl; abstr 3).