NEW ORLEANS—The combination of bendamustine and rituximab improves progression-free and complete response rates while showing a better tolerability profile, when compared with CHOP plus rituximab (CHOP-R) as first-line treatment of patients with advanced follicular, indolent, and mantle cell lymphomas, according to data reported here at the ASH Annual Meeting.
Median progression-free survival time improved by 20 months with bendamustinerituximab, and the complete response rate improved by approximately one third.
These promising results, from a Phase III trial by the German Study Group Indolent Lymphomas (StiL), suggest that bendamustine-rituximab has the potential to become a new standard first-line treatment option for patients with these lymphomas, the researchers said.
Mathias J. Rummel, MD, PhD, Head of the Department of Hematology at University Hospital in Giessen, Germany, presented final results of the multicenter, randomized Phase III study, noting that the results built on the promising Phase II results of bendamustine-rituximab in relapsed/ refractory indolent or mantle cell lymphomas, published in the Journal of Clinical Oncology in 2005.
Overall response rates in the Phase III trial were similar, with a median observation time of 32 months: 93.8% for bendamustinerituximab vs 93.5% for CHOP-R.
In the primary endpoint of progressionfree survival, bendamustine-rituximab was superior to CHOP-R, with median progression- free survivals of 54.9 vs. 34.8 months, respectively.
“The complete response rate was significantly higher with in the bendamustine- rituximab group, 40.1%, compared with 30.8% for CHOP-R,” Dr. Rummel reported.
Bendamustine-rituximab was also superior to CHOP-R in event-free survival—54 months for bendamustine-rituximab vs 31 months for CHOP-R.
In time to next treatment, the median had not yet been reached in the bendamustinerituximab group, and was 40.7 months for CHOP-R.
Overall survival did not differ between the two groups at this point of time. Dr. Rummel said there would probably not be an increase in overall survival soon, because of the very indolent nature of the disease. As of the time of his report at the meeting, he said, 67 patients had died—34 in the bendamustine-rituximab group and 33 in the CHOP-R group.
Dr. Rummel reported on 513 patients, median age of 64, approximately three-quarters of whom had Stage IV disease, with the majority of the rest having Stage III. Patients received either rituximab at 375 mg/m2 on Day 1 plus either bendamustine at 90 mg/m2 (Days 1 and 2) every 28 days (260 patients) or the standard CHOP regimen every 21 days for a maximum of six cycles (253 patients).
Prophylactic use of antibiotics or growth factors were not generally recommended in this protocol. Six cycles of bendamustinerituximab were given in 82% of those patients and 86% of the CHOP-R patients.
CHOP-R treatment was more frequently associated with serious adverse events, Dr. Rummel said: 74 events in that group vs only 49 with bendamustine-rituximab. And significant differences in hematologic toxicities were observed for neutropenia Grade 3/4 (10.7% with bendamustinerituximab 10.7% vs 46.5% for CHOP-R) and for leukocytopenia Grade 3/4 (12.1% for bendamustine-rituximab vs 38.2% for CHOP-R).
And G-CSF was more often used in the CHOP-R group, 20.0% of all cycles, compared with 4.0% in the bendamustinerituximab group.
Alopecia, which Dr. Rummel said will occur in most patients receiving CHOPR, occurred in only 15% of bendamustine- rituximab patients versus 62% with CHOP-R.
There were fewer infectious complications associated with bendamustine-rituximab than with CHOP-R (95 vs 121); a lower incidence of peripheral neuropathy (18 vs 73); and fewer episodes of stomatitis (16 vs 47).
Drug-associated erythematous skin reactions (urticaria, rash) were the only side effects seen more often with bendamustinerituximab than with CHOP-R: 42 vs 23.
The moderator of a news conference that featured the study, Richard Van Etten, MD PhD, Professor of Medicine at Tufts University School of Medicine and Chief of the Division of Hematology/Oncology at Tufts Medical Center, interviewed afterwards, called the research potentially practice changing, given that this is first-line treatment for advanced disease.
“Based on both the superior toxicity profile of the bendamustine-rituximab combination, and the surprising superiority in terms of efficacy—although there is no overall survival data yet—clinicians should definitely consider bendamustinerituximab as potentially the new frontline treatment for this disease,” he said.
In an OTBroadcast News podcast from the ASH meeting, George Canellos, MD, Professor of Medicine at Harvard Medical School, noted that bendamustine-rituximab has the advantage of being two single agents, abrogating the need for combination chemotherapy. Still, he pointed to a potential downside to the combination, that of cost, which he said he believed in North America could be considerable.
Mathias Rummel talks more about his study using bendamustine rather than CHOP combined with rituximab for treating indolent lymphomas as front-line therapy in a “Live from ASH” OT Broadcast News podcast (Program #3) available at oncology-times.com and on iTunes. Also commenting are George Canellos and Richard Van Etten.