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Carfilzomib, Lenalidomide, and Dexamethasone for Relapsed Multiple Myeloma A. Keith Stewart, M.B., Ch.B., S. Vincent Rajkumar, M.D., Meletios A. Dimopoulos, M.D., Tamás Masszi, M.D., Ph.D., Ivan Špička, M.D., Ph.D., Albert Oriol, M.D., Roman Hájek, M.D., Ph.D., Laura Rosiñol, M.D., Ph.D., David S. Siegel, M.D., Ph.D., Georgi G. Mihaylov, M.D., Ph.D., Vesselina Goranova-Marinova, M.D., Ph.D., Péter Rajnics, M.D., Ph.D., Aleksandr Suvorov, M.D., Ruben Niesvizky, M.D., Andrzej J. Jakubowiak, M.D., Ph.D., Jesus F. San-Miguel, M.D., Ph.D., Heinz Ludwig, M.D., Michael Wang, M.D., Vladimír Maisnar, M.D., Ph.D., Jiri Minarik, M.D., Ph.D., William I. Bensinger, M.D., Maria-Victoria Mateos, M.D., Ph.D., Dina Ben-Yehuda, M.D., Vishal Kukreti, M.D., Naseem Zojwalla, M.D., Margaret E. Tonda, Pharm.D., Xinqun Yang, Ph.D., Biao Xing, Ph.D., Philippe Moreau, M.D., and Antonio Palumbo, M.D., for the ASPIRE Investigators*
A BS T R AC T Background The authors’ affiliations are listed in the Appendix. Address reprint requests to Dr. Stewart at the Division of Hematology– Oncology, Mayo Clinic, 13400 E. Shea Blvd., Scottsdale, AZ 85259, or at stewart.keith@ mayo.edu. *A complete list of investigators in the Carfilzomib, Lenalidomide, and Dexamethasone versus Lenalidomide and Dexamethasone for the Treatment of Patients with Relapsed Multiple Myeloma (ASPIRE) study is provided in the Supplementary Appendix, available at NEJM.org. This article was published on December 6, 2014, at NEJM.org. N Engl J Med 2015;372:142-52. DOI: 10.1056/NEJMoa1411321 Copyright © 2014 Massachusetts Medical Society.
Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma. The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma. Methods
We randomly assigned 792 patients with relapsed multiple myeloma to carfilzomib with lenalidomide and dexamethasone (carfilzomib group) or lenalidomide and dexamethasone alone (control group). The primary end point was progression-free survival. Results
Progression-free survival was significantly improved with carfilzomib (median, 26.3 months, vs. 17.6 months in the control group; hazard ratio for progression or death, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P = 0.0001). The median overall survival was not reached in either group at the interim analysis. The Kaplan–Meier 24-month overall survival rates were 73.3% and 65.0% in the carfilzomib and control groups, respectively (hazard ratio for death, 0.79; 95% CI, 0.63 to 0.99; P = 0.04). The rates of overall response (partial response or better) were 87.1% and 66.7% in the carfilzomib and control groups, respectively (P<0.001; 31.8% and 9.3% of patients in the respective groups had a complete response or better; 14.1% and 4.3% had a stringent complete response). Adverse events of grade 3 or higher were reported in 83.7% and 80.7% of patients in the carfilzomib and control groups, respectively; 15.3% and 17.7% of patients discontinued treatment owing to adverse events. Patients in the carfilzomib group reported superior health-related quality of life. Conclusions
In patients with relapsed multiple myeloma, the addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk–benefit profile. (Funded by Onyx Pharmaceuticals; ClinicalTrials.gov number, NCT01080391.) 142
n engl j med 372;2 nejm.org january 8, 2015
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