Rituximab has been shown to prolong survival when used with chemotherapy in CLL. The findings come from a comparative analysis of two completed national phase II and phase III clinical trials. A study of with Treanda (bendamustine)was published in the Journal of Clinical Oncology in May 2005 showed significant activity of Treanda and Rituxan® (Rituximab) for the treatment of relapsed or refractory low-grade NHL or mantle cell lymphoma. A multicenter U.S. and Canadian trial of Treanda evaluated Treanda in combination with Rituxan in 67 patients with indolent or mantle cell lymphoma who had failed chemotherapy was presented at ASH 2005. Thirty-seven per cent had also failed Rituxan. The overall response rate was 87% with complete responses observed in 33%. The most frequent complications were related to reversible myelotoxicity.
In a Phase II clinical trial, the combination of Treanda® (bendamustine) and Rituxan® (rituximab) produced promising results among patients with relapsed chronic lymphocytic leukemia (CLL). These results were presented at the 50th Annual Meeting of the American Society of Hematology. German researchers have also performed a randomized trial comparing BOP (bendamustine, oncovin and prednisone) to COP (cyclophosphamide, oncovin and prednisone) in a randomized trial of 513 patients with untreated indolent and mantle-cell lymphoma who were randomly assigned to bendamustine/rituximab (BR) or R-CHOP, and the initial results were presented at the 2009 American Society of Hematology annual meeting. All patients with FL (N = 279, median age 60) had deﬁned indications for treatment. The overall response rate with BR was 93%, and the complete response rate and progression-free survival were superior to those seen with R-CHOP. These results have led to a new trial comparing the efficacy of Treanda and Rituxan to Fludara® (fludarabine), Cytoxan® (cyclophosphamide) and Rituxan for treatment of newly diagnosed patients, NCT00769522. This randomized phase III trial is studying fludarabine, cyclophosphamide, and rituximab to see how well they work compared with bendamustine and rituximab in treating patients with previously untreated B-cell chronic lymphocytic leukemia. In this study, Treanda and Rituxan are the standard arm.
Treanda is now FDA approved. On October 31, 2008, the U.S. Food and Drug Administration (FDA) approved bendamustine hydrochloride (TREANDA®, Cephalon, Inc.), an intravenously administered alkylating agent, for the treatment of patients with indolent B-cell non-Hodgkin lymphoma (NHL) that progressed during or within six months of treatment with rituximab or a rituximab-containing regimen.
The combination regimen of Treanda and Rituxan has strong guideline support. Category 1 evidence in the NCCN guidelines indicates that the decision for including the recommendation is based on results of randomised, controlled clinical trials. It is the highest level of evidence in the guidelines. Category 2A suggests the committee had issues with the evidence but generally accepted it. In 2011, NCCN changed its recommendation form category 2A to category 1. The change in evidence level was based on the STIL NHL 1-2003 trial in which the combination of rituximab and bendamustine was compared with a standard chemotherapy regimen of rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone. With a mean observation period of 34 months, the 260 patients with various lymphoma histologies who were treated with the bendamustine-based therapy achieved a progression-free survival of 54.9 months compared with 34.8 months for the 253 patients who received the multiple drug combination therapy.
The 2014 NCCN treatment guideline recommends the following:
•Treanda as a single agent as initial therapy for CLL
•Treanda as a single agent or in combination with Rituxan® (rituximab) for treatment of CLL that has recurred following prior therapy (second-line therapy.
•Treanda with or without Rituxan as first-line therapy for follicular lymphoma or mantle-cell lymphoma (p.FOLL-B) and this is a category 1 recommendation.
Thus, there is both an FDA approval for follicular lymphoma under the more general name of “low-grade lymphoma” and a specific NCCN recommendation.
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