Publication details

Bortezomib-Based Therapy for Newly Diagnosed Mantle-Cell Lymphoma

Authors

ROBAK Tadeusz HUANG Huiqiang JIN Jie ZHU Jun LIU Ting SAMOILOVA Olga PYLYPENKO Halyna VERHOEF Gregor SIRITANARATKUL Noppadol OSMANOV Evgenii ALEXEEVA Julia PEREIRA Juliana DRACH Johannes MAYER Jiří HONG Xiaonan OKAMOTO Rumiko PEI Lixia ROONEY Brendan VELDE Helgi van de CAVALLI Franco

Year of publication 2015
Type Article in Periodical
Magazine / Source New England Journal of Medicine
MU Faculty or unit

Faculty of Medicine

Citation
Doi http://dx.doi.org/10.1056/NEJMoa1412096
Field Oncology and hematology
Keywords RELAPSED MULTIPLE-MYELOMA; EUROPEAN-MCL-NETWORK; PERIPHERAL NEUROPATHY; RANDOMIZED-TRIALS; PHASE-2 PINNACLE; PROGNOSTIC INDEX; FREE SURVIVAL; RITUXIMAB; VINCRISTINE; CYCLOPHOSPHAMIDE
Description 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.)

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