Tadeusz RobakHuiqiang HuangJie JinJun ZhuTing LiuOlga SamoilovaHalyna PylypenkoGregor VerhoefNoppadol SiritanaratkulEvgenii OsmanovJulia AlexeevaJuliana PereiraJohannes DrachJiri MayerXiaonan HongRumiko OkamotoLixia PeiBrendan RooneyHelgi Van De VeldeFranco CavalliMedical University of LodzSun Yat-Sen University Cancer CenterZhejiang University School of MedicineBeijing Cancer HospitalWest China Hospital of Sichuan UniversityFudan University Shanghai Cancer CenterNizhny Novgorod Regional HospitalN.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical SciencesFederal Center of HeartCherkassy Regional Oncology CenterKU Leuven– University Hospital LeuvenJanssen Research and DevelopmentMahidol UniversityUniversidade de Sao Paulo - USPMedizinische Universitat WienFakultni Nemocnice BrnoTokyo Metropolitan Komagome HospitalJanssenJanssen Research and DevelopmentOspedale San Giovanni2018-11-232018-11-232015-03-05New England Journal of Medicine. Vol.372, No.10 (2015), 944-95315334406002847932-s2.0-84924439988https://repository.li.mahidol.ac.th/handle/20.500.14594/36495Copyright © 2015 Massachusetts Medical Society. Background The proteasome inhibitor bortezomib was initially approved for the treatment of relapsed mantle-cell lymphoma. We investigated whether substituting bortezomib for vincristine in frontline therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) could improve outcomes in patients with newly diagnosed mantle-cell lymphoma. Methods In this phase 3 trial, we randomly assigned 487 adults with newly diagnosed mantlecell lymphoma who were ineligible or not considered for stem-cell transplantation to receive six to eight 21-day cycles of R-CHOP intravenously on day 1 (with prednisone administered orally on days 1 to 5) or VR-CAP (R-CHOP regimen, but replacing vincristine with bortezomib at a dose of 1.3 mg per square meter of body-surface area on days 1, 4, 8, and 11). The primary end point was progression-free survival. Results After a median follow-up of 40 months, median progression-free survival (according to independent radiologic review) was 14.4 months in the R-CHOP group versus 24.7 months in the VR-CAP group (hazard ratio favoring the VR-CAP group, 0.63; P<0.001), a relative improvement of 59%. On the basis of investigator assessment, the median durations of progression-free survival were 16.1 months and 30.7 months, respectively (hazard ratio, 0.51; P<0.001), a relative improvement of 96%. Secondary end points were consistently improved in the VR-CAP group, including the complete response rate (42% vs. 53%), the median duration of complete response (18.0 months vs. 42.1 months), the median treatment-free interval (20.5 months vs. 40.6 months), and the 4-year overall survival rate (54% vs. 64%). Rates of neutropenia and thrombocytopenia were higher in the VR-CAP group. Conclusions VR-CAP was more effective than R-CHOP in patients with newly diagnosed mantlecell lymphoma but at the cost of increased hematologic toxicity.Mahidol UniversityMedicineArticleSCOPUS10.1056/NEJMoa1412096