The randomized phase III ELOQUENT-2 study (NCT01239797) evaluated the efficacy and safety of elotuzumab + lenalidomide/dexamethasone (ELd) versus lenalidomide/dexamethasone (Ld) in relapsed/refractory multiple myeloma. ELd reduced the risk of disease progression/death by 30% versus Ld (hazard ratio [HR] 0·70). Median time from diagnosis was 3·5 years. We present extended 3-year follow-up data. Endpoints included progression-free survival (PFS), overall response rate (ORR) and interim overall survival (OS). Exploratory post-hoc analyses included impact of time from diagnosis and prior lines of therapy on PFS, and serum M-protein dynamic modelling. ORR was 79% (ELd) and 66% (Ld) (P = 0·0002). ELd reduced the risk of disease progression/death by 27% versus Ld (HR 0·73; P = 0·0014). Interim OS demonstrated a trend in favour of ELd (P = 0·0257); 1-, 2- and 3-year rates with ELd versus Ld were: 91% versus 83%, 73% versus 69% and 60% versus 53%. In patients with ≥ median time from diagnosis and one prior therapy, ELd resulted in a 53% reduction in the risk of progression/death versus Ld (HR 0·47). Serum M-protein dynamic modelling showed slower tumour regrowth with ELd. Adverse events were comparable between arms. ELd provided a durable and clinically relevant improvement in efficacy, with minimal incremental toxicity.

1st Department of Medicine Department of Haematology 1st Faculty of Medicine Charles University and General Teaching Hospital Prague Prague Czech Republic

AbbVie Biotherapeutics Inc Redwood City CA USA

Clinica Universidad de Navarra Investigación Médica Aplicada IDISNA CIBERONC Pamplona Spain

Clinical Pharmacology and Pharmacometrics Bristol Myers Squibb Lawrenceville NJ USA

Davidoff Cancer Center Rabin Medical Center Petah Tikva Israel

Department of Cancer Prevention Medical University of Silesia Katowice Poland

Department of Clinical Therapeutics National and Kapodistrian University of Athens School of Medicine Athens Greece

Department of Haemato oncology and Bone Marrow Transplantation Medical University of Lublin Lublin Poland

Department of Haematology Ankara University Ankara Turkey

Department of Haematology University Hospital Nantes France

Department of Hematology and Medical Oncology Winship Cancer Institute Emory University School of Medicine Atlanta GA USA

Department of Medical Oncology and Haematology Princess Margaret Cancer Centre Toronto ON Canada

Department of Medical Oncology Dana Farber Cancer Institute Boston MA USA

Department of Oncology Cross Cancer Institute and University of Alberta Edmonton AB Canada

Division of Hematologic Oncology Dana Farber Cancer Institute Boston MA USA

Division of Hematology Queen Elizabeth 2 Health Sciences Centre and Dalhousie University Halifax NS Canada

Global Biometric Sciences Bristol Myers Squibb Lawrenceville NJ USA

Global Biostatistics Bristol Myers Squibb Lawrenceville NJ USA

Global Clinical Research Bristol Myers Squibb Lawrenceville NJ USA

Haematology Department University Hospital of Salamanca Instituto de Investigación Biomédica de Salamanca Salamanca Spain

Institute of Haematology Assuta Medical Centers Tel Aviv Israel

Myeloma Unit Division of Haematology University of Torino Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino Torino Italy

Oncology Clinical Development Bristol Myers Squibb Lawrenceville NJ USA

See more in PubMed

Amgen (2016) FDA approves new Kyprolis® (carfilzomib) combination therapy for the treatment of patients with relapsed or refractory multiple myeloma. Available at: http://www.amgen.com/media/news-releases/2016/01/fda-approves-new-kyprolis-carfilzomib-combination-therapy-for-the-treatment-of-patients-with-relapsed-or-refractory-multiple-myeloma/. (accessed 1 August 2016).

Collins, S.M. , Bakan, C.E. , Swartzel, G.D. , Hofmeister, C.C. , Efebera, Y.A. , Kwon, H. , Starling, G.C. , Ciarlariello, D. , Bhaskar, S. , Briercheck, E.L. , Hughes, T. , Yu, J. , Rice, A. & Benson, D.M. Jr (2013) Elotuzumab directly enhances NK cell cytotoxicity against myeloma via CS1 ligation: evidence for augmented NK cell function complementing ADCC. Cancer Immunology, Immunotherapy, 62, 1841–1849. PubMed PMC

Dimopoulos, M.A. , Chen, C. , Spencer, A. , Niesvizky, R. , Attal, M. , Stadtmauer, E.A. , Petrucci, M.T. , Yu, Z. , Olesnyckyj, M. , Zeldis, J.B. , Knight, R.D. & Weber, D.M. (2009) Long‐term follow‐up on overall survival from the MM‐009 and MM‐010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia, 23, 2147–2152. PubMed

Dimopoulos, M.A. , Oriol, A. , Nahi, H. , San‐Miguel, J. , Bahlis, N.J. , Usmani, S.Z. , Rabin, N. , Orlowski, R.Z. , Komarnicki, M. , Suzuki, K. , Plesner, T. , Yoon, S.S. , Ben, Y.D. , Richardson, P.G. , Goldschmidt, H. , Reece, D. , Lisby, S. , Khokhar, N.Z. , O'Rourke, L. , Chiu, C. , Qin, X. , Guckert, M. , Ahmadi, T. & Moreau, P. (2016) Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. New England Journal of Medicine, 375, 1319–1331. PubMed

Durie, B.G. , Harousseau, J.L. , Miguel, J.S. , Blade, J. , Barlogie, B. , Anderson, K. , Gertz, M. , Dimopoulos, M. , Westin, J. , Sonneveld, P. , Ludwig, H. , Gahrton, G. , Beksac, M. , Crowley, J. , Belch, A. , Boccadaro, M. , Cavo, M. , Turesson, I. , Joshua, D. , Vesole, D. , Kyle, R. , Alexanian, R. , Tricot, G. , Attal, M. , Merlini, G. , Powles, R. , Richardson, P. , Shimizu, K. , Tosi, P. , Morgan, G. & Rajkumar, S.V. (2006) International uniform response criteria for multiple myeloma. Leukemia, 20, 1467–1473 [erratum in: Leukemia, 2007; 21, 1134; Leukemia, 2006; 20, 2220]. PubMed

Food and Drug Administration (2016a) FDA approves Darzalex for patients with previously treated multiple myeloma. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm472875.htm (accessed 1 August 2016).

Food and Drug Administration (2016b) FDA approves Empliciti, a new immune‐stimulating therapy to treat multiple myeloma. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm474684.htm (accessed 1 August 2016).

Food and Drug Administration (2016c). FDA approves Ninlaro, new oral medication to treat multiple myeloma. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm473771.htm (accessed 1 August 2016).

Hsi, E.D. , Steinle, R. , Balasa, B. , Szmania, S. , Draksharapu, A. , Shum, B.P. , Huseni, M. , Powers, D. , Nanisetti, A. , Zhang, Y. , Rice, A.G. , van Abbema, A. , Wong, M. , Liu, G. , Zhan, F. , Dillon, M. , Chen, S. , Rhodes, S. , Fuh, F. , Tsurushita, N. , Kumar, S. , Vexler, V. , Shaughnessy, J.D. Jr , Barlogie, B. , van Rhee, F. , Hussein, M. , Afar, D.E. & Williams, M.B. (2008) CS1, a potential new therapeutic antibody target for the treatment of multiple myeloma. Clinical Cancer Research, 14, 2775–2784. PubMed PMC

Lonial, S. , Dimopoulos, M. , Palumbo, A. , White, D. , Grosicki, S. , Spicka, I. , Walter‐Croneck, A. , Moreau, P. , Mateos, M.V. , Magen, H. , Belch, A. , Reece, D. , Beksac, M. , Spencer, A. , Oakervee, H. , Orlowski, R.Z. , Taniwaki, M. , Rollig, C. , Einsele, H. , Wu, K.L. , Singhal, A. , San‐Miguel, J. , Matsumoto, M. , Katz, J. , Bleickardt, E. , Poulart, V. , Anderson, K.C. & Richardson, P. (2015) Elotuzumab therapy for relapsed or refractory multiple myeloma. New England Journal of Medicine, 373, 621–631. PubMed

National Cancer Institute (2015) FDA approval for elotuzumab. Available at: http://www.cancer.gov/about-cancer/treatment/drugs/elotuzumab. (accessed 1 August 2016).

Stewart, A.K. , Rajkumar, S.V. , Dimopoulos, M.A. , Masszi, T. , Spicka, I. , Oriol, A. , Hajek, R. , Rosinol, L. , Siegel, D.S. , Mihaylov, G.G. , Goranova‐Marinova, V. , Rajnics, P. , Suvorov, A. , Niesvizky, R. , Jakubowiak, A.J. , San‐Miguel, J.F. , Ludwig, H. , Wang, M. , Maisnar, V. , Minarik, J. , Bensinger, W.I. , Mateos, M.V. , Ben‐Yehuda, D. , Kukreti, V. , Zojwalla, N. , Tonda, M.E. , Yang, X. , Xing, B. , Moreau, P. & Palumbo, A. (2015) Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. New England Journal of Medicine, 372, 142–152. PubMed

Wang, Y. , Sung, C. , Dartois, C. , Ramchandani, R. , Booth, B.P. , Rock, E. & Gobburu, J. (2009) Elucidation of relationship between tumor size and survival in non‐small‐cell lung cancer patients can aid early decision making in clinical drug development. Clinical Pharmacology & Therapeutics, 86, 167–174. PubMed

Wolchok, J.D. , Hoos, A. , O'Day, S. , Weber, J.S. , Hamid, O. , Lebbe, C. , Maio, M. , Binder, M. , Bohnsack, O. , Nichol, G. , Humphrey, R. & Hodi, F.S. (2009) Guidelines for the evaluation of immune therapy activity in solid tumors: immune‐related response criteria. Clinical Cancer Research, 15, 7412–7420. PubMed

Elotuzumab, lenalidomide, and dexamethasone in RRMM: final overall survival results from the phase 3 randomized ELOQUENT-2 study

Insights on Multiple Myeloma Treatment Strategies

Interpreting clinical trial data in multiple myeloma: translating findings to the real-world setting