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| |  ASCO: Rituximab Plus CHOP Effective as First Line Therapy for Mantle Cell Lymphoma and as Maintenance Therapy for Indolent Lymphoma By Peggy Peck NEW ORLEANS, LA -- June 7, 2004 -- Rituximab plus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) significantly increased the rate of complete remission and the overall response in patients with mantle cell lymphoma (MCL), according to results presented here on June 5th at the American Society of Clinical Oncology the 40th Annual Meeting. Moreover, in a second study maintenance therapy with rituximab slowed progression of advanced indolent non-Hodgkin's lymphoma. Patients randomized to the combination of CHOP and rituximab had a 34% complete remission rate versus a 7% rate in patients treated with CHOP alone, said lead investigator Martin Dreyling, MD, Professor of Medicine, University Hospital Grosshadern LMU, University of Munich, Munich, Germany. He said, however, that "the survival was no different in both arms at 22 months -- 85% in both arms." The study enrolled 122 patients with newly diagnosed MCL stages III and IV. Sixty patients were randomized to CHOP plus rituximab and 62 to CHOP alone. "This benefit had no significant cost in side effects, thus it may be considered as a new baseline regimen," said Dr. Dreyling. The infection rates in both arms were 1%, but white cell deficiency occurred more often among patients in the rituximab plus CHOP arm. In the second study, 74% patients taking maintenance rituximab after first-line chemotherapy for advanced indolent non-Hodgkin's had no evidence of disease progression after 2 years on the drug, while 42% of patients who didn't take the drug had evidence of progression. Lead author of the study, Howard S. Hochster, MD, professor of medicine at the New York University School of Medicine, New York, New York, said the effect was greater than expected and he suggested that it "may be the best treatment strategy." In the study 154 patients were randomized to 4 doses of rituximab 375 mg/m2 every 6 months for 2 years beginning 4 weeks after their final chemotherapy cycle, and 149 patients did not receive maintenance therapy. In light of the positive findings of the both studies, Dr. Hochster was asked if all lymphoma patients should be considered for rituximab treatment, either in combination with CHOP or as a maintenance regimen. "That is a difficult decision. Aggressive lymphomas are more likely to be curable and more likely to respond to treatment, but it does appear that rituximab has wide activity," he said. He said, however, that more studies are needed before wide-ranging recommendations can be made. Both studies were funded by Genentech, Inc, Biogen Idec Inc, and Roche.
[Presentation title: "Effect of the addition of rituximab to front line therapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) on the remission rate and time to treatment failure (TTF) compared to CHOP alone in mantle cell lymphoma (MCL): Results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG)." Abstract #6501."Results of E1496: A phase III trial of CVP with or without maintenance rituximab in advanced indolent lymphoma (NHL)." Abstract #6502]
6500 Randomized intergroup trial of first line treatment for patients <=60 years with diffuse large B-cell non-Hodgkin's lymphoma (DLBCL) with a CHOP-like regimen with or without the anti-CD20 antibody rituximab -- early stopping after the first interim analysis.
M. G. Pfreundschuh, L. Trümper, D. Ma, A. Österborg, R. Pettengell, M. Trneny, L. Shepherd, J. Waleswski, P.-L. Zinzani, M. Loeffler; Saarland University Medical School, Homburg, Germany; DSHNHL, Homburg, Germany; Australasian Leukaemia and Lymphoma Group ALLG, Sidney, Australia; Swedish Lymphoma Group, Stockholm, Sweden; Britsih National Lymphoma Investigation, London, United Kingdom; Charles University, Prague, Czech Republic; NCI-Canada Lymphoma Group, Homburg, Germany; Polish Lymphoma Group, Warszawa, Poland; Italian Northern Lymphoma Group, Bologna, Italy
Background: While rituximab improved outcome in elderly patients with DLBCL (Coiffier et al., 2002), there is no data for young low-risk patients. Methods: In a randomized study conducted in 18 countries, untreated patients (18-60 years) with low-risk DLBCL (IPI 0 or 1, stages II-IV and stage I with bulk) were randomized to 6 cycles of a CHOP-like regimen (CHEMO) or the same chemotherapy plus rituximab 375 mg/m2 given on days 1, 22, 43, 64, 85, and 106 (R-CHEMO). Radiotherapy was planned to initial bulk and/or extranodal involvement. The primary endpoint was time to treatment failure (TTF) with events defined as failure to achieve complete remission, progressive disease, relapse, or death. The trial was powered to show a 10% difference in TTF rate after 3 years. Results: Between 05/2000 and 10/2003, 824 patients were recruited. The first planned interim analysis was performed on 326 evaluable patients with confirmed CD20 positive DLBCL (median age 48 years; IPI=1: 56%, 24% stage III/IV disease, 32% elevated LDH, 50% bulk). Toxicity was not different in the two arms. R-CHEMO patients had a significantly longer TTF (p=0.00003; log rank test) and overall survival (p=0.0057; log rank test) than CHEMO pateints. At a median observation time of 15 months, TTF rates were 84.0% for R-CHEMO and 62.5% for CHEMO. R-CHEMO patients had a higher complete remission rate (84.7% vs. 66.0%; p=0.0003) and a lower rate of progressive disease (6.3% vs. 17.7%; p=0.0039). As the empirical p-value of the log rank test statistic for TTF was considerably lower than the critical value for the interim analysis (pcrit=0.00105), the formal criterion for stopping the trial was met. Therefore, the DSMB recommended the early termination of the treatment phase of the trial in 12/2003 with 45/824 patients still under chemotherapy. Conclusions: The results of the MInT trial indicate that the addition of rituximab to 6 cycles of a CHOP-like regimen significantly improves TTF, CR rates, and OS in young patients with low-risk DLBCL.
6501 Effect of the addition of rituximab to front line therapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) on the remission rate and time to treatment failure (TTF) compared to CHOP alone in mantle cell lymphoma (MCL): Results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG).
W. Hiddemann, M. Dreyling, M. Unterhalt, R. Repp, S. Hermann, A. Haenel, B. Metzner, C. Pott, F. Hartmann, R. Parwaresch; Ludwig-Maximilians-University, München, Germany
Background: MCL is a disease of higher age and carries a bad prognosis with a median survival of only 3 to 4 years. New treatment modalities are therefore warranted. Based on the highly encouraging results of combining Rituximab with the Fludarabine, Cyclophosphamide, Mitoxantrone (FCM) regimen for salvage therapy of relapsed MCL, the GLSG embarked on a prospective randomised trial comparing CHOP versus Rituximab plus CHOP (R-CHOP) for first line therapy. Methods: 122 consecutive patients with newly diagnosed MCL of stages III and IV were randomised between CHOP versus R-CHOP. Results: Of the 122 patients 60 were randomised to CHOP and 62 to R-CHOP. A significantly higher rate of CR of 34% vs. 7% (p=0.00024) and of CR + PR of 94% versus 75% (p=0.005) was achieved for R-CHOP vs. CHOP treated patients. In addition, TTF was significantly longer (p=0.0131) while the time to progression was not statistically different. No differences were observed either within the two postremission strategies between R-CHOP or CHOP treated cases. Treatment associated side effects comprised predominantly myelosuppression and granulocytopenia in particular. Grade III and IV granulocytopenia was more frequent after R-CHOP (63% versus 53%, p=0.01). This was clinically not of major relevance, however, since severe infections were observed after 5% and 7% of courses, only. Conclusions: R-CHOP induces remissions in almost all patients with previously untreated MCL and prolongs the time to treatment failure significantly over CHOP alone. R-CHOP is a highly effective, well tolerated regimen for front line therapy of MCL.
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