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BACKGROUND	The proteasome inhibitor bortezomib was initially approved for the treatment of relapsed mantle-cell lymphoma .
BACKGROUND	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 mantle-cell 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 ) .
METHODS	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 % .
RESULTS	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 % .
RESULTS	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 % ) .
RESULTS	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 mantle-cell lymphoma but at the cost of increased hematologic toxicity .
CONCLUSIONS	( Funded by Janssen Research and Development and Millennium Pharmaceuticals ; LYM-3002 ClinicalTrials.gov number , NCT00722137 . )

