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 mantle-cell lymphoma who were ineligible or not considered for stem-cell transplantation to receive six to eight 21-day cycles ofR-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 mantle-cell lymphoma but at the cost of increased hematologic toxicity. (Funded by Janssen Research and Development and Millennium Pharmaceuticals; LYM-3002 ClinicalTrials.gov number, NCT00722137.).
RCT Entities:
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 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). 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 mantle-cell lymphoma but at the cost of increased hematologic toxicity. (Funded by Janssen Research and Development and Millennium Pharmaceuticals; LYM-3002 ClinicalTrials.gov number, NCT00722137.).
Authors: Jia Ruan; Peter Martin; Bijal Shah; Stephen J Schuster; Sonali M Smith; Richard R Furman; Paul Christos; Amelyn Rodriguez; Jakub Svoboda; Jessica Lewis; Orel Katz; Morton Coleman; John P Leonard Journal: N Engl J Med Date: 2015-11-05 Impact factor: 91.245
Authors: Ilja Bobylev; Dominik Peters; Maulik Vyas; Mohammed Barham; Ines Klein; Elke Pogge von Strandmann; Wolfram F Neiss; Helmar C Lehmann Journal: Neurotox Res Date: 2017-06-13 Impact factor: 3.911
Authors: Erin G Reid; David Looney; Frank Maldarelli; Ariela Noy; David Henry; David Aboulafia; Juan Carlos Ramos; Joseph Sparano; Richard F Ambinder; Jeannette Lee; Ethel Cesarman; Sara Yahyaei; Ronald Mitsuyasu; William Wachsman Journal: Blood Adv Date: 2018-12-26
Authors: Jeff D Wang; Samuel G Katz; Elizabeth A Morgan; David T Yang; Xueliang Pan; Mina L Xu Journal: Hum Pathol Date: 2019-08-16 Impact factor: 3.466
Authors: Stephen E Spurgeon; Brian G Till; Peter Martin; Andre H Goy; Martin P Dreyling; Ajay K Gopal; Michael LeBlanc; John P Leonard; Jonathan W Friedberg; Lawrence Baizer; Richard F Little; Brad S Kahl; Mitchell R Smith Journal: J Natl Cancer Inst Date: 2016-12-31 Impact factor: 13.506
Authors: Brian G Till; Hongli Li; Steven H Bernstein; Richard I Fisher; W Richard Burack; Lisa M Rimsza; Justin D Floyd; Marco A DaSilva; Dennis F Moore; Olga Pozdnyakova; Sonali M Smith; Michael LeBlanc; Jonathan W Friedberg Journal: Br J Haematol Date: 2015-10-22 Impact factor: 6.998