PS1370 ELOTUZUMAB PLUS POMALIDOMIDE AND DEXAMETHASONE FOR RELAPSED/REFRACTORY MULTIPLE MYELOMA: EFFICACY RESULTS AFTER ADDITIONAL FOLLOW‐UP OF THE PHASE 2, RANDOMIZED ELOQUENT‐3 STUDY
Authors: Dimopoulos M. , Dytfeld D. , Grosicki S. , Moreau P. , Takezako N. , Hori M. , Leleu X. , LeBlanc R. , Suzuki K. , Raab M.S. , Richardson P.G. , McKiver M. Popa , Jou Y.‐M. , Shelat S.G. , Robbins M. , Rafferty B. , Miguel J. San 
Published: June 2019

Please indicate where the abstract has been published before: The primary analysis of ELOQUENT‐3, with preliminary overall survival data, was reported in Dimopoulos MA et al. N Engl J Med 2018;379:1811–22.Background:Despite multiple therapeutic options for multiple myeloma (MM), duration of disease control decreases with each line of therapy and overall survival (OS) remains poor after treatment failure with proteasome inhibitors (PIs) and immunomodulatory drugs (Kumar SK et al. Leukemia 2017). Elotuzumab, an immunostimulatory monoclonal antibody targeting SLAMF7, enables selective killing of MM cells through multiple mechanisms of action and synergizes with the immunomodulatory drug pomalidomide (pom). The primary analysis (minimum follow‐up [FU]: 9.1 months) of the open‐label, randomized, ELOQUENT‐3 study (NCT02654132) demonstrated a median progression‐free survival (PFS) of 10.3 months for elotuzumab plus pom and dexamethasone (EPd) vs 4.7 mo for pom and dex (Pd) alone (HR 0.54, p = 0.008). Preliminary analysis of OS suggested a trend in favor of EPd (Dimopoulos MA et al. N Engl J Med 2018). On the basis of these data, EPd was approved in the United States for the treatment of adult patients (pts) with MM and ≥2 prior therapies including lenalidomide (len) and a PI.Aims:This non‐prespecified analysis was conducted to provide a descriptive assessment of OS with EPd vs Pd in ELOQUENT‐3 after extended FU. PFS and safety were also assessed.Methods:Eligible pts were adults with ≥2 prior lines of therapy (LoTs), including len and a PI (prior pom not permitted), who had MM that was refractory to last therapy and either refractory or relapsed and refractory to len and a PI. Pts were randomized 1:1 (stratified by prior LoTs [2–3 vs ≥4] and ISS stage at study entry [I–II vs III]) to receive EPd or Pd in 28‐day cycles until disease progression or unacceptable toxicity. Elotuzumab: 10 mg/kg IV weekly in cycles 1–2 and 20 mg/kg IV every 4 weeks in cycles 3+. Pom: 4 mg orally on days 1–21 of each cycle. Dexamethasone: 40 mg (pts ≤75 years) or 20 mg (pts >75 years) weekly in each cycle. Primary endpoint was PFS per investigator assessment; secondary endpoints were overall response rate per investigator and OS. All pts provided written informed consent.Results:In total, 60 pts were randomized to the EPd group and 57 to the Pd group. Clinically relevant baseline characteristics were balanced between treatment groups; median (range) age was 67 (36–81) years. Median (range) number of prior LoTs was 3 (2–8), and 68% (EPd) and 72% (Pd) of pts had MM that was refractory to both len and a PI. As of clinical data cut‐off (29 Nov 2018, minimum FU 18.3 mo), there were a total of 90 PFS events (EPd: 40/60; Pd: 50/57). PFS rates (EPd vs Pd) were 43% vs 20% (12 mo) and 34% vs 11% (18 mo). In this updated assessment after 48 (EPd: 20/60; Pd: 28/57) of the 78 (62%) deaths required for the final analysis, OS curves continued to diverge, with a 46% reduction in the risk of death with EPd vs Pd (HR 0.54, 95% CI 0.30–0.96; Figure). Median (95% CI) OS was not reached (24.9–not estimable [NE]) with EPd and was 17.4 mo (13.8–NE) with Pd. OS rates (EPd vs Pd) were 79% vs 68% (12 mo) and 68% vs 49% (18 mo). Safety results were consistent with the primary analysis.Summary/Conclusion:In this extended FU of ELOQUENT‐3, EPd demonstrated sustained and clinically relevant PFS and OS benefits vs Pd, with no new safety signals. These data support the long‐term favorable efficacy–safety profile of EPd and suggest this regimen could be considered as a standard of care for pts with relapsed/refractory MM after failure of len and a PI.image