As reported in the Journal of Clinical Oncology by Meletios A. Dimopoulos, MD, and colleagues, the final overall survival analysis of the phase II ELOQUENT-3 trial showed significant benefit with the addition of elotuzumab to pomalidomide and dexamethasone (EPd) vs pomalidomide and dexamethasone alone (Pd) in patients with relapsed or refractory multiple myeloma who were previously treated with lenalidomide and a proteasome inhibitor.
The primary analysis of the trial showed significantly prolonged progression-free survival with EPd vs Pd (hazard ratio [HR] = 0.54, 95% confidence interval [CI] = 0.34–0.86, P = .008). The primary analysis supported the November 2018 approval of elotuzumab in combination with Pd in this setting.
Meletios A. Dimopoulos, MD
Study Details
In the international open-label trial, 117 patients with disease refractory to the last treatment received were randomly assigned between March 2016 and April 2017 to receive EPd (n = 60) or Pd (n = 57). Treatment was given in 28-day cycles, with elotuzumab given at 10 mg/kg once daily on days 1, 8, 15, and 22 during cycles 1 and 2 and at 20 mg/kg once daily on day 1 of each subsequent cycle. All patients received pomalidomide at 4 mg once daily on days 1 through 21 of each cycle and oral dexamethasone at 40 mg (20 mg in those aged > 75 years) once weekly; on days of elotuzumab administration, patients in the EPd group received both oral (28 mg; 8 mg in those aged > 75 years) and intravenous (8 mg) dexamethasone.
Key Findings
At data cutoff (January 2021), minimum follow-up was 45 months. Among the 60 patients in the EPd group and the 55 patients in the Pd group who received study treatment, 37 in the EPd group (61.7%) and 41 in the Pd group (74.5%) died. The most common cause of death in both groups was disease progression (41.7% and 49.1%). Median overall survival was 29.8 months (95% confidence interval [CI] = 22.9–45.7 months) in the EPd group vs 17.4 months (95% CI = 13.8–27.7 months) in the Pd group (hazard ratio = 0.59, 95% CI = 0.37–0.93, P = .0217). Overall survival rates at 1, 2, and 3 years were 79% vs 68%, 63% vs 44%, and 39% vs 29%.
After study therapy, subsequent systemic therapy was received by 70.0% of patients in the EPd group vs 68.4% of the Pd group, with the most common in both groups being daratumumab (43.3% vs 43.9%), followed by carfilzomib (30.0% vs 28.1%), and cyclophosphamide (25.0% vs 24.6%).
No new safety signals were detected.
The investigators concluded: “EPd demonstrated a statistically significant improvement in overall survival vs Pd in patients with relapsed or refractory multiple myeloma previously treated with lenalidomide and a proteasome inhibitor 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 progression-free survival and overall survival significantly.”
Meletios A. Dimopoulos, MD, of National and Kapodistrian University of Athens School of Medicine, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by Bristol Myers Squibb and AbbVie Biotherapeutics. For full disclosures of the study authors, visit ascopubs.org.
