CHICAGO—Progression-free survival more than doubled and tolerability improved in patients with previously untreated indolent lymphoma and in elderly patients with mantle cell lymphoma treated with a combination of bendamustine and rituximab, compared with patients treated with the standard R-CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab) in the front-line setting, according to data reported at the ASCO Annual Meeting (Abstract 3).
With a median follow-up of 45 months, median progression-free survival in the bendamustine-rituximab group was 69.5 months, vs. 31.2 months for the R-CHOP group, with a hazard ratio of 0.58.
Results from the long-term multicenter Phase III German Study Group for Indolent Lymphomas (StiL) NHL1 study were presented by lead author Mathias J. Rummel, MD, PhD, Head of the Department of Hematology in the Clinic for Hematology and Medical Oncology at Justus-Liebig University-Hospital in Germany.
Bruce J. Roth, MD, the moderator of a news conference related to the four plenary papers, said, “It's certainly remarkable to have an agent that provides superior efficacy and decreased toxicity at the same time.” Roth, Professor of Medicine in the Division of Oncology at Washington University School of Medicine in St. Louis, noted that some U.S. physicians had already switched to this regimen after preliminary data from this trial were presented at the American Society of Hematology's 2009 Annual Meeting (OT, 2/10/10 issue).
“But it's nice to have the final data, and this is likely to become a standard of care for these individuals,” he said.
That thought was also confirmed by the study's Discussant, Michael E. Williams, MD, Professor and Chief of the Division of Hematology/Oncology at the University of Virginia Medical Center: “StiL NHL1 establishes bendamustine-rituximab as a front-line regimen for patients with indolent B-cell and nontransplant-eligible mantle cell lymphoma, providing equivalent or better responses versus R-CHOP, with less toxicity,” he said.
Developed in East Germany
Bendamustine, first synthesized in the former East Germany in 1963, was a well-kept secret behind the Iron Curtain, Rummel said in jest during the news conference. When the drug was first introduced in the West it was viewed skeptically because of its development in a Communist country, he said.
Bendamustine became available in the United States only in 2008, and in the European Union, in 2010. R-CHOP is still the regimen of choice in the United States and in much of Europe.
“R-CHOP is a very established regimen in the treatment of lymphoma; it has an absolute place in the diffuse large B-cell lymphoma setting, but there was always a debate about whether you need such an aggressive treatment in patients with indolent lymphomas,” Rummel explained.
And he said that while bendamustine-rituximab is approved for use in patients with rituximab-refractory disease, he knows that many physicians are using it off-label in the first-line setting—“Nobody is waiting until patients become rituximab-refractory,” he said.
PFS More Than Doubled
The data presented at the ASCO meeting were from an updated analysis on 514 evaluable patients—261 in the bendamustine-rituximab arm and 253 receiving R-CHOP, as of October 2011. With a median follow-up of 45 months, median progression-free survival in the bendamustine-rituximab group was 69.5 months, vs. only 31.2 months for the R-CHOP group, with a hazard ratio 0.58.
The progression-free survival rates were superior with bendamustine-rituximab in patients with all histological subtypes except marginal zone lymphoma, he said.
And the improved PFS with bendamustine-rituximab was similar for patients age 60 or younger (hazard ratio 0.52) and for those over 60 (hazard ratio 0.62).
In patients with normal levels of lactate dehydrogenase (62% of those in the study), PFS was significantly prolonged with use of bendamustine-rituximab compared with R-CHOP, while in the elevated LDH group (38%), progression-free survival was numerically but not significantly increased with bendamustine-rituximab compared with R-CHOP.
In patients with follicular lymphoma, Follicular Lymphoma International Prognostic Index subgroups defined by 0–2 factors (favorable) and 3–5 factors (unfavorable) had a longer progression-free survival with bendamustine-rituximab than with R-CHOP. The overall response rate was 92.7 percent in the bendamustine-rituximab group (261 patients) versus 91.3 percent in the R-CHOP group (253 patients). The difference in complete response was almost 40 percent with bendamustine-rituximab versus 30 percent with R-CHOP.
Toxicities Less with Bendamustine-Rituximab
Rummel reported a more favorable tolerability profile for bendamustine-rituximab than for R-CHOP: less severe neutropenia, 29 vs. 69 percent, respectively; and no alopecia in the group taking bendamustine-rituximab. There was also a lower incidence of neurotoxicity, and a significantly lower incidence of paresthesia, stomatitis, and infections.
But patients on bendamustine-rituximab had a higher incidence of severe lymphocytopenia compared with those receiving R-CHOP (74% vs. 43%); and a relatively higher incidence of all-grade skin reactions (40% vs. 15%, respectively).
No difference has been seen in overall survival to date, with 43 and 45 deaths in the bendamustine-rituximab and R-CHOP, respectively, he said, explaining that this was likely due to the protracted nature of indolent lymphomas and the use of salvage therapies for patients with progressive disease.
Similarly, the number of secondary malignancies: 20 with bendamustine-rituximab and 23 in the R-CHOP group, including one hematologic malignancy in each group—one case of myelodysplastic syndrome in the patients receiving bendamustine-rituximab, and one of acute myelogenous leukemia in patients on R-CHOP.