Approval Overview
Recently, the Committee for Medicinal Products for Human Use (CHMP) of the European Union has granted a positive opinion for the triple combination therapy: Empliciti (elotuzumab) plus Pomalyst (pomalidomide) and low-dose dexamethasone (EPd).
This regimen is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma (R/R MM) who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI), and have demonstrated disease progression on the last therapy.
The same combination therapy was approved by the U.S. Food and Drug Administration (FDA) for this indication in November of the previous year.
Basis for Approval: ELOQUENT‑3 Phase 2 Study
Study Design
The positive CHMP opinion was supported by data from the Phase 2 clinical study ELOQUENT‑3.The study enrolled 117 patients with relapsed/refractory multiple myeloma who had failed at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI).
The primary objective was to evaluate whether the EPd regimen had superior efficacy and safety compared with the standard-of-care doublet regimen (pomalidomide plus dexamethasone, Pd).
Initial Efficacy Results
Data from the ELOQUENT‑3 study showed:
Progression‑Free Survival (PFS): Median PFS was significantly longer in the EPd group than in the Pd group (10.25 months [95% CI: 5.59 months – not estimable] vs 4.67 months [95% CI: 2.83 months – 7.16 months]).
Risk reduction: The risk of disease progression or death was significantly reduced by 46% in the EPd group (HR = 0.54, 95% CI: 0.34–0.86, p = 0.0078).
Safety Profile
The incidence of serious adverse reactions was 22% in the EPd group, compared with 15% in the Pd group.
Updated Results from EHA 2019
Updated data from ELOQUENT‑3 were presented at the 24th Annual Congress of the European Hematology Association (EHA 2019).
Results showed that patients treated with the EPd regimen continued to derive sustained, clinically meaningful benefits in overall survival (OS) and PFS compared with those receiving the Pd regimen:
Overall Survival: The risk of death was significantly reduced by 46% in the EPd group (HR = 0.54; 95% CI: 0.30–0.96).
At 18 months, the OS rate was 68% in the EPd group vs 49% in the Pd group.
Median OS had not yet been reached in the EPd group (95% CI: 29.4 months – NE), compared with 17.4 months (95% CI: 13.8 – NE) in the Pd group.
Progression‑Free Survival rate at 18 months: 34% for EPd vs 11% for Pd.
Clinical Outlook
It is hoped that the Empliciti‑based triple combination regimen will benefit more patients with multiple myeloma who are relapsed or refractory to prior therapies.
