Elotuzumab Plus Pomalidomide and Dexamethasone for Relapsed/Refractory Multiple Myeloma: Final Overall Survival Analysis From the Randomized Phase II ELOQUENT-3 Trial

• Published in: Journal of Clinical Oncology Vol. 41; no. 3; pp. 568 - 578
• Main Authors: Dimopoulos, Meletios A., Dytfeld, Dominik, Grosicki, Sebastian, Moreau, Philippe, Takezako, Naoki, Hori, Mitsuo, Leleu, Xavier, LeBlanc, Richard, Suzuki, Kenshi, Raab, Marc S., Richardson, Paul G., Popa McKiver, Mihaela, Jou, Ying-Ming, Yao, David, Das, Prianka, San-Miguel, Jesús
• Format: Journal Article
• Language: English
• Published: United States American Society of Clinical Oncology (ASCO) 20.01.2023; Wolters Kluwer Health
• Subjects: Antineoplastic Combined Chemotherapy Protocols; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Dexamethasone; Elotuzumab; Humans; Lenalidomide; Multiple Myeloma; Multiple Myeloma - drug therapy; ORIGINAL REPORTS; Pomalidomide/dexamethasone (EPd); Pomalidomide/dexamethasone (Pd); Progression-free survival (PFS); Survival Analysis
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/jco.21.02815

PURPOSEIn the phase II ELOQUENT-3 trial (ClinicalTrials.gov identifier: NCT02654132), elotuzumab combined with pomalidomide/dexamethasone (EPd) significantly improved progression-free survival (PFS) versus pomalidomide/dexamethasone (Pd) in patients with relapsed/refractory multiple myeloma (RRMM) previously treated with lenalidomide and a proteasome inhibitor (PI). Here, we present the final overall survival (OS) results.METHODSPatients with RRMM who had received ≥ 2 prior lines of therapy, with disease refractory to last therapy and either refractory or relapsed and refractory to lenalidomide and a PI were randomly assigned (1:1) to receive EPd or Pd. The primary end point was PFS per investigator assessment. ORR and OS were secondary end points planned to be tested hierarchically.RESULTSA total of 117 patients were randomly assigned to EPd (n = 60) and Pd (n = 57). Among treated patients (EPd 60, Pd 55), there were 37 (61.7%) deaths in the EPd group and 41 (74.5%) in the Pd group, most commonly because of disease progression (EPd 41.7%, Pd 49.1%). Median (95% CI) OS was significantly improved with EPd (29.8 [22.9 to 45.7] months) versus Pd (17.4 [13.8 to 27.7] months), with a hazard ratio of 0.59 (95% CI, 0.37 to 0.93; P = .0217). OS benefit with EPd was observed in most patient subgroups. The safety profile of EPd was consistent with prior reports with no new safety signals detected.CONCLUSIONEPd demonstrated a statistically significant improvement in OS versus Pd in patients with RRMM previously treated with lenalidomide and a PI who had disease refractory to last therapy. In this setting, ELOQUENT-3 is the first randomized study of a triplet regimen incorporating a monoclonal antibody and Pd to improve both PFS and OS significantly.