Lenalidomide plus Dexamethasone for Relapsed Multiple Myeloma in North America
Donna M. Weber, M.D., Christine Chen, M.D., Ruben Niesvizky, M.D., Michael Wang, M.D., Andrew Belch, M.D., Edward A. Stadtmauer, M.D., David Siegel, M.D., Ivan Borrello, M.D., S. Vincent Rajkumar, M.D., Asher Alban Chanan-Khan, M.D., Sagar Lonial, M.D., Zhinuan Yu, Ph.D., John Patin, M.S., Marta Olesnyckyj, R.N., Jerome B. Zeldis, M.D., Ph.D., Robert D. Knight, M.D., for the Multiple Myeloma (009) Study Investigators
Background Lenalidomide, an oral immunomodulatory drug thatis similar to thalidomide but has a different safety profile,has clinical activity in relapsed or refractory multiple myeloma.
Methods Patients in the United States and Canada who had receivedat least one previous therapy for multiple myeloma but who requiredadditional treatment were randomly assigned to receive either25 mg of lenalidomide or placebo on days 1 to 21 of a 28-daycycle. Both groups also received 40 mg of oral dexamethasoneon days 1 to 4, 9 to 12, and 17 to 20 for the first four cycles.After the fourth cycle, 40 mg of dexamethasone was administeredonly on days 1 to 4. Safety, clinical response, time to progression,and overall survival were assessed.
Results We assigned 177 patients to the lenalidomide group and176 to the placebo group. Complete, near-complete, or partialresponses occurred in 108 patients (61.0%) in the lenalidomidegroup and in 35 patients (19.9%) in the placebo group (P<0.001);complete responses occurred in 14.1% and 0.6%, respectively(P<0.001). The median time to progression was 11.1 monthsin the lenalidomide group and 4.7 months in the placebo group(P<0.001). Median overall survival times in the two groupswere 29.6 months and 20.2 months, respectively (P<0.001).Grade 3 or 4 adverse events were reported in 85.3% of the lenalidomidegroup and in 73.1% of the placebo group; these events resultedin study discontinuation in 19.8% and 10.2%, respectively. Grade3 or 4 neutropenia and venous thromboembolism were more commonin the lenalidomide group than in the placebo group (41.2% vs.4.6% and 14.7% vs. 3.4%, respectively; P<0.001 for both comparisons).
Conclusions Lenalidomide plus dexamethasone is superior to placeboplus dexamethasone in patients with relapsed or refractory multiplemyeloma. (ClinicalTrials.gov number, NCT00056160
[ClinicalTrials.gov]
.)
Source Information
From the M.D. Anderson Cancer Center, Houston (D.M.W., M.W.); Princess Margaret Hospital, Toronto (C.C.); Weill Cornell Medical College, New York (R.N.); Cross Cancer Institute, Edmonton, AB, Canada (A.B.); University of Pennsylvania Cancer Center, Philadelphia (E.A.S.); the Cancer Center at Hackensack University Medical Center, Hackensack, NJ (D.S.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (I.B.); Mayo Clinic Cancer Center, Rochester, MN (S.V.R.); Roswell Park Cancer Institute, Buffalo, NY (A.A.C.-K.); Emory University, Atlanta (S.L.); and Celgene, Summit, NJ (Z.Y., J.P., M.O., J.B.Z., R.D.K.).
Address reprint requests to Dr. Weber at the Department of Lymphoma and Myeloma, M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Box 429, Houston, TX 77030, or at dmweber{at}mdanderson.org.
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