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著者: H C Kluin-Nelemans, E Hoster, O Hermine, J Walewski, M Trneny, C H Geisler, S Stilgenbauer, C Thieblemont, U Vehling-Kaiser, J K Doorduijn, B Coiffier, R Forstpointner, H Tilly, L Kanz, P Feugier, M Szymczyk, M Hallek, S Kremers, G Lepeu, L Sanhes, J M Zijlstra, R Bouabdallah, P J Lugtenburg, M Macro, M Pfreundschuh, V Procházka, F Di Raimondo, V Ribrag, M Uppenkamp, M André, W Klapper, W Hiddemann, M Unterhalt, M H Dreyling
雑誌名: N Engl J Med. 2012 Aug 9;367(6):520-31. doi: 10.1056/NEJMoa1200920.
Abstract/Text
BACKGROUND: The long-term prognosis for older patients with mantle-cell lymphoma is poor. Chemoimmunotherapy results in low rates of complete remission, and most patients have a relapse. We investigated whether a fludarabine-containing induction regimen improved the complete-remission rate and whether maintenance therapy with rituximab prolonged remission.
METHODS: We randomly assigned patients 60 years of age or older with mantle-cell lymphoma, stage II to IV, who were not eligible for high-dose therapy to six cycles of rituximab, fludarabine, and cyclophosphamide (R-FC) every 28 days or to eight cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 21 days. Patients who had a response underwent a second randomization to maintenance therapy with rituximab or interferon alfa, each given until progression.
RESULTS: Of the 560 patients enrolled, 532 were included in the intention-to-treat analysis for response, and 485 in the primary analysis for response. The median age was 70 years. Although complete-remission rates were similar with R-FC and R-CHOP (40% and 34%, respectively; P=0.10), progressive disease was more frequent with R-FC (14%, vs. 5% with R-CHOP). Overall survival was significantly shorter with R-FC than with R-CHOP (4-year survival rate, 47% vs. 62%; P=0.005), and more patients in the R-FC group died during the first remission (10% vs. 4%). Hematologic toxic effects occurred more frequently in the R-FC group than in the R-CHOP group, but the frequency of grade 3 or 4 infections was balanced (17% and 14%, respectively). In 274 of the 316 patients who were randomly assigned to maintenance therapy, rituximab reduced the risk of progression or death by 45% (in remission after 4 years, 58%, vs. 29% with interferon alfa; hazard ratio for progression or death, 0.55; 95% confidence interval, 0.36 to 0.87; P=0.01). Among patients who had a response to R-CHOP, maintenance therapy with rituximab significantly improved overall survival (4-year survival rate, 87%, vs. 63% with interferon alfa; P=0.005).
CONCLUSIONS: R-CHOP induction followed by maintenance therapy with rituximab is effective for older patients with mantle-cell lymphoma. (Funded by the European Commission and others; ClinicalTrials.gov number, NCT00209209.).
PMID 22873532 N Engl J Med. 2012 Aug 9;367(6):520-31. doi: 10.1056/NEJMoa1200920.
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