Bortezomib plus Melphalan and Prednisone for Initial Treatment of Multiple Myeloma
Jesús F. San Miguel, M.D., Ph.D., Rudolf Schlag, M.D., Nuriet K. Khuageva, M.D., Ph.D., Meletios A. Dimopoulos, M.D., Ofer Shpilberg, M.D., Ph.D., Martin Kropff, M.D., Ivan Spicka, M.D., Ph.D., Maria T. Petrucci, M.D., Antonio Palumbo, M.D., Olga S. Samoilova, M.D., Ph.D., Anna Dmoszynska, M.D., Ph.D., Kudrat M. Abdulkadyrov, M.D., Ph.D., Rik Schots, M.D., Ph.D., Bin Jiang, M.D., Maria-Victoria Mateos, M.D., Ph.D., Kenneth C. Anderson, M.D., Dixie L. Esseltine, M.D., Kevin Liu, Ph.D., Andrew Cakana, M.D., Helgi van de Velde, M.D., Ph.D., Paul G. Richardson, M.D., for the VISTA Trial Investigators
Background The standard treatment for patients with multiplemyeloma who are not candidates for high-dose therapy is melphalanand prednisone. This phase 3 study compared the use of melphalanand prednisone with or without bortezomib in previously untreatedpatients with multiple myeloma who were ineligible for high-dosetherapy.
Methods We randomly assigned 682 patients to receive nine 6-weekcycles of melphalan (at a dose of 9 mg per square meter of body-surfacearea) and prednisone (at a dose of 60 mg per square meter) ondays 1 to 4, either alone or with bortezomib (at a dose of 1.3mg per square meter) on days 1, 4, 8, 11, 22, 25, 29, and 32during cycles 1 to 4 and on days 1, 8, 22, and 29 during cycles5 to 9. The primary end point was the time to disease progression.
Results The time to progression among patients receiving bortezomibplus melphalan–prednisone (bortezomib group) was 24.0months, as compared with 16.6 months among those receiving melphalan–prednisonealone (control group) (hazard ratio for the bortezomib group,0.48; P<0.001). The proportions of patients with a partialresponse or better were 71% in the bortezomib group and 35%in the control group; complete-response rates were 30% and 4%,respectively (P<0.001). The median duration of the responsewas 19.9 months in the bortezomib group and 13.1 months in thecontrol group. The hazard ratio for overall survival was 0.61for the bortezomib group (P=0.008). Adverse events were consistentwith established profiles of toxic events associated with bortezomiband melphalan–prednisone. Grade 3 events occurred in ahigher proportion of patients in the bortezomib group than inthe control group (53% vs. 44%, P=0.02), but there were no significantdifferences in grade 4 events (28% and 27%, respectively) ortreatment-related deaths (1% and 2%).
Conclusions Bortezomib plus melphalan–prednisone was superiorto melphalan–prednisone alone in patients with newly diagnosedmyeloma who were ineligible for high-dose therapy. (ClinicalTrials.govnumber, NCT00111319
[ClinicalTrials.gov]
.)
Source Information
The authors' affiliations are listed in the Appendix.
Address reprint requests to Dr. San Miguel at Hospital Universitario de Salamanca, Paseo San Vicente 58-182, 37007 Salamanca, Spain, or at sanmigiz{at}usal.es.
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