Results of a Prospective Randomised Open Label Phase III Study Comparing Rituximab Plus Mitoxantrone, Chlorambucile, Prednisolone Chemotherapy (R-MCP) Versus MCP Alone in Untreated Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) and Mantle-Cell-Lymphoma (MCL).
Author:
Herold Michael12, Pasold Rita2, Srock Stefanie2, Neser Sabine2, Niederwieser Dietger2, Neubauer Andreas2, Dölken Gottfried2, Naumann Ralph2, Fietz Thomas2, Freund Mathias2, Rohrberg Robert2, Hoeffken Klaus2, Franke Astrid2, Ittel Thomas H.2, Kettner Erika2, Haak Ursula2, Mey Ullrich2, Klinkenstein Christian2, Assmann Michael2, von Gruenhagen Ullrich2, Dachselt Klaus2, Schwenke Helga2, Bleyl Dorothee2, Wolf Heiner2, Hahnfeld Sabine2, Hoffmann Franz-Adolph2, Lakner Volker2, Richter Peter2, Hähling Detlev2, Wolf H. H.2, Eschenburg Henning2, Clemens M.-R.2, Grobe Norbert2
Affiliation:
1. 2nd Medical Department, Div. Hematology/Oncology, HELIOS Klinikum Erfurt, Erfurt, Germany 2. East German Study Group Hematology/Oncology (OSHO), Leipzig, Germany
Abstract
Abstract
Rituximab proved to be effective in relapsed and refractory indolent NHL as a single agent and generated impressive results in phase II studies in combination with chemotherapy. In a prospective randomized trial we compared the efficacy and toxicity of rituximab (375 mg/m² d 1) plus MCP-chemotherapy ( mitoxantrone 8 mg/m² d 3 + 4, chlorambucile 3 x 3 mg/m² d 3 – 7, prednisolone 25 mg/m² d 3 – 7 ) given every 28 days for a total of 8 cycles versus MCP (d 1 – 5) x 8 cycles alone in advanced indolent NHL and MCL. Efficacy endpoints included overall and complete response rates, event free survival, progression free survival, overall survival and toxicity. For response assessment classical definitions have been used. Between 10/98 and 09/03 we randomized 358 patients (pts) with advanced stage follicular lymphoma (FL) (grade 1 + 2), lymphoplasmacytic lymphoma and MCL to either R-MCP or MCP. The study arms are well balanced for all demographic factors. 201/358 pts (56%) had FL. Both regimens were well tolerated with a low incidence of serious adverse events. The overall response rate (RR) and the complete response rate (CR) for all pts was 85,5% and 42% in the R-MCP arm versus 65,5% and 20% in the MCP arm (p<0,0001). Results were even more impressive in the subgroup of FL pts (n=201) with an overall RR of 92,4% and a CR rate of 49,5% for R-MCP versus 75% and 25% for MCP alone respectively (p<0,0001). In the overall group event free survival (EFS) was significantly prolonged for pts receiving R-MCP vs MCP alone (p<0,001). Median EFS for MCP was 19 months, at this time point EFS for R-MCP was 73%. In FL pts the median EFS for MCP is 19 months too and EFS was 86% for R-MCP at this point. 2-year EFS for all pts was 69% for R-MCP versus 44% for MCP; for FL pts the respective 2-year EFS was 83% for R-MCP and 43% for MCP (p’s<0,0001) (Kaplan Maier estimates). These results compare favourably with the recntly published data of immunochemotherapy for treatment of NHL or MCL. The results from our study confirm the superiority of a combination of rituximab and chemotherapy in the first- line treatment of indolent NHL, primarily follicular lymphoma. The CR rates achieved with the R-MCP regimen are impressive, especially since stricter response criteria were used. In summary we conclude, that the addition of rituximab to MCP chemotherapy improves significantly the outcome of pts with indiolent NHL and MCL.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
Cited by
60 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|