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Bendamustine-Rituximab Doubles Progression-Free Survival in Indolent Lymphomas


 

FROM THE ANNUAL MEETING OF THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY

CHICAGO – Bendamustine-rituximab continues to outshine CHOP-rituximab for indolent and mantle cell lymphomas, based on the updated results of the StiL NHL1 study.

With a twofold higher rate of progression-free survival and several-fold reductions in the rates of associated toxicities, "bendamustine-rituximab could be considered the preferred first-line treatment for patients with these disease entities," Dr. Mathias J. Rummel said during a press conference at the annual meeting of the American Society of Clinical Oncology.

Bendamustine is marketed in the United States as Treanda (Cephalon). Bendamustine was developed 50 years ago in East Germany, Dr. Rummel said. Only after the reunification of Germany did physicians in the West learn about the drug and begin to conduct clinical trials and to publish the results.

A large randomized trial of 514 evaluable patients treated in community and hospital-based oncology groups in Germany, StiL NHL1 compared progression-free survival for the two regimens in patients with follicular, Waldenstrom’s, marginal zone, small lymphocytic, or mantle cell lymphomas.

Patients in the bendamustine-rituximab group had a median of 69.5 months of progression-free survival compared with 31.2 months with CHOP-rituximab. The benefit with bendamustine-rituximab was maintained in all histological subtypes except marginal zone lymphoma.

In patients with normal levels of lactic dehydrogenase (62%), progression-free survival was significantly prolonged with bendamustine-rituximab compared with CHOP-rituximab (P less than .001). In those with elevated levels of LDH (38%), progression-free survival was numerically, but not significantly, increased with bendamustine-rituximab (P = .118).

In patients with follicular lymphoma, follicular lymphoma international prognostic index (FLIPI) subgroups defined by 0-2 factors (favorable) and 3-5 factors (unfavorable) had longer progression-free survival with bendamustine-rituximab than with CHOP-rituximab. The longer progression-free survival was significant for both the favorable (P = .043) and unfavorable (P = .068) FLIPI subgroups.

Patients in the study were randomized for a maximum of six cycles to either bendamustine (90 mg/m2 on day 1 and 2) and rituximab (375 mg/m2 on day 1) or to CHOP-rituximab (cyclophosphamide 750 mg/m2 on day 1, doxorubicin 50 mg/m2 on day 1, vincristine 1.4 mg/m2 on day 1, and prednisone 100 mg on days 1-5), and rituximab (375 mg/m2 on day 1), according to Dr. Rummel of the University Hospital Giessen (Germany).

In the bendamustine-rituximab group, 74 salvage treatments had been initiated. In the CHOP-rituximab group, 116 salvage treatments were initiated. Of those in the CHOP-rituximab group, 52 patients received bendamustine-rituximab as a salvage regimen. Overall survival did not differ between the treatment arms, with 43 and 45 deaths in the two groups, respectively. Secondary malignancies were observed in 20 patients in the bendamustine-rituximab group compared with 23 in the CHOP-rituximab group, with 1 hematologic malignancy in each group (1 case of myelodysplastic syndrome in the bendamustine-rituximab group and 1 case of acute myelogenous leukemia in the CHOP-rituximab group).

Grade 3/4 hematotoxicities were significantly lower in the 261 patients in the bendamustine-rituximab group than in the 253 in the CHOP-rituximab group (P less than .0001). The percentage of cycles associated with leukopenia was 12% for bendamustine-rituximab patients and 38% for CHOP-rituximab patients. The percentage of cycles associated with neutropenia was nearly 11% with bendamustine-rituximab and more than 46% with CHOP-rituximab. The percentage of cycles that necessitated administration of granulocyte colony-stimulating factor (G-CSF) was 4% with bendamustine-rituximab and 20% with CHOP-rituximab. The rates of anemia and thrombocytopenia were comparable and low (less than 2% of cycles) for both regimens.

Importantly, alopecia did not occur with bendamustine-rituximab but was nearly universal with CHOP-rituximab, Dr. Rummel said. Paresthesias were noted in 18 of 261 bendamustine-rituximab patients and 73 of 253 CHOP-rituximab patients; stomatitis was seen in 16 and 73 patients, respectively. Both differences were significant (P less than .0001).

Conversely, the bendamustine-treated patients had more erythema (42 of 261 bendamustine-rituximab patients vs. 23 of 253 CHOP-rituximab patients) and allergic reactions (40 vs. 15, respectively). These were not dose-limiting toxicities. Infectious complications were frequent, and affected 96 bendamustine and 127 CHOP patients.

Next steps include a new trial called MAINTAIN that will examine rituximab maintenance therapy in 591 patients treated with bendamustine and rituximab. Patients will receive 2 years of rituximab maintenance therapy and will then be randomized to either observation or 2 more years of rituximab.

Dr. Rummel receives honoraria and research funding from Mundipharma and Roche.

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