Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma
Lonial S(1), Dimopoulos M, Palumbo A, White D, Grosicki S, Spicka I, Walter-Croneck A, Moreau P, Mateos MV, Magen H, Belch A, Reece D, Beksac M, Spencer A, Oakervee H, Orlowski RZ, Taniwaki M, Röllig C, Einsele H, Wu KL, Singhal A, San-Miguel J, Matsumoto M, Katz J, Bleickardt E, Poulart V, Anderson KC, Richardson P; ELOQUENT-2 Investigators.
(1) From Winship Cancer Institute, Emory University School of Medicine, Atlanta (S.L.); National and Kapodistrian University of Athens, Athens (M.D.); A.O.U. San Giovanni Battista di Torino-Ospedale Molinette, Turin, Italy (A.P.); QEII Health Science Center and Dalhousie University, Halifax, NS (D.W.), Cross Cancer Institute and University of Alberta, Edmonton (A.B.), and Princess Margaret Cancer Centre, Toronto (D.R.) - all in Canada; Silesian Medical University, Katowice (S.G.), and Medical University of Lublin, Lublin (A.W.-C.) - both in Poland; Charles University Hospital, Prague, Czech Republic (I.S.); University Hospital, Nantes, France (P.M.); Complejo Asistencial Universitario de Salamanca-Instituto de Investigación Biomédica de Salamanca, Salamanca (M.-V.M.), and Clinica Universidad de Navarra-Centro de Investigación Médica Aplicada, Instituto de Investigación Sanitaria de Navarra, Pamplona (J.S.-M.) - both in Spain; Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, and Tel Aviv University, Ramat Aviv - both in Israel (H.M.); Ankara University, Ankara, Turkey (M.B.); Alfred Health-Monash University, Melbourne, VIC, Australia (A. Spencer); Barts and the London NHS Trust, London (H.O.); University of Texas M.D. Anderson Cancer Center, Houston (R.Z.O.); Kyoto Prefectural University of Medicine, Kyoto (M.T.), and Nishigunma National Hospital, Shibukawa (M.M.) - both in Japan; Universitätsklinikum der Technische Universität, Dresden (C.R.), and Universitätsklinikum Würzburg, Würzburg (H.E.) - both in Germany; Zeikenhuis Netwerk Antwerpen (ZNA) Stuivenberg, Antwerp, Belgium (K.L.W.); AbbVie Biotherapeutics, Redwood City, CA (A. Singhal); Bristol-Myers Squibb, Princeton, NJ (J.K.), Wallingford, CT (E.B.), and Braine-l'Alleud, Belgium (V.P.); and Dana-Farber Cancer Institute, Boston (K.C.A., P.R.).
Background Elotuzumab, an immunostimulatory monoclonal antibody targeting signaling lymphocytic activation molecule F7 (SLAMF7), showed activity in combination with lenalidomide and dexamethasone in a phase 1b-2 study in patients with relapsed or refractory multiple myeloma.
Methods In this phase 3 study, we randomly assigned patients to receive either elotuzumab plus lenalidomide and dexamethasone (elotuzumab group) or lenalidomide and dexamethasone alone (control group). Coprimary end points were progression-free survival and the overall response rate. Final results for the coprimary end points are reported on the basis of a planned interim analysis of progression-free survival.
Results Overall, 321 patients were assigned to the elotuzumab group and 325 to the control group. After a median follow-up of 24.5 months, the rate of progression-free survival at 1 year in the elotuzumab group was 68%, as compared with 57% in the control group; at 2 years, the rates were 41% and 27%, respectively. Median progression-free survival in the elotuzumab group was 19.4 months, versus 14.9 months in the control group (hazard ratio for progression or death in the elotuzumab group, 0.70; 95% confidence interval, 0.57 to 0.85; P<0.001). The overall response rate in the elotuzumab group was 79%, versus 66% in the control group (P<0.001). Common grade 3 or 4 adverse events in the two groups were lymphocytopenia, neutropenia, fatigue, and pneumonia. Infusion reactions occurred in 33 patients (10%) in the elotuzumab group and were grade 1 or 2 in 29 patients.
Conclusions Patients with relapsed or refractory multiple myeloma who received a combination of elotuzumab, lenalidomide, and dexamethasone had a significant relative reduction of 30% in the risk of disease progression or death. (Funded by Bristol-Myers Squibb and AbbVie Biotherapeutics; ELOQUENT-2 ClinicalTrials.gov number, NCT01239797 .).
CITATION N Engl J Med. 2015 Jun 2.