EHA 2018: Elotuzumab Plus Pomalidomide and Low-Dose Dexamethasone vs Pomalidomide/Dexamethasone Alone in Relapsed or Refractory Multiple Myeloma
The ELOQUENT-3 trial, an international phase II study evaluating the addition of elotuzumab (Empliciti) to pomalidomide (Pomalyst) and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma, achieved its primary endpoint, showing a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for patients treated with elotuzumab plus pomalidomide and dexamethasone compared with pomalidomide and dexamethasone alone. ELOQUENT-3 is the only randomized, active-controlled trial to investigate a pomalidomide-based triplet combination in patients with relapsed/refractory multiple myelona who received at least two prior therapies, including lenalidomide (Revlimid) and a proteasome inhibitor.
These findings were presented by Dimopoulos et al at the 23rd Annual Congress of the European Hematology Association (EHA) (Abstract LB2606).
Findings
Patients randomized to elotuzumab plus pomalidomide and dexamethasone experienced a 46% reduction in risk of disease progression (hazard ratio [HR] = 0.54; 95% confidence interval [CI] = 0.34–0.86, P = .0078) compared with patients randomized to pomalidomide and dexamethasone alone, with median PFS of 10.3 months (95% CI = 5.6–not estimable) compared with 4.7 months (95% CI = 2.8–7.2) in pomalidomide and dexamethasone patients. The PFS benefit experienced among patients randomized to elotuzumab plus pomalidomide and dexamethasone was consistent among patients who had received two to three prior lines of therapy (HR = 0.55; 95% CI = 0.31–0.98) and four or more prior lines of therapy (HR = 0.51; 95% CI = 0.24–1.08). The safety profile for elotuzumab plus pomalidomide and dexamethasone was consistent with prior findings for elotuzumab and pomalidomide regimens.
“The ELOQUENT-3 trial is the first randomized trial comparing the standard of care, pomalidomide and low-dose dexamethasone, with and without the addition of a monoclonal antibody. These data support the hypothesis that the addition of elotuzumab to pomalidomide and dexamethasone elicits a synergistic effect and prolongs, significantly, the progression-free survival of heavily pretreated patients with myeloma, regardless of the number of prior therapies,” said Meletios A. Dimopoulos, MD, Professor and Chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens, School of Medicine. “We believe that elotuzumab plus pomalidomide and low-dose dexamethasone, if approved by regulatory authorities, could become an important potential treatment option for patients with relapsed/refractory multiple myeloma whose disease has progressed after treatment with lenalidomide and a proteasome inhibitor.”
Twice as many patients randomized to elotuzumab plus pomalidomide and dexamethasone responded to therapy compared to patients randomized to pomalidomide and dexamethasone alone. Patients randomized to elotuzumab plus pomalidomide and dexamethasone demonstrated an overall response rate (ORR) of 53% (95% CI = 40–66), compared with 26% (95% CI = 16–40) among patients randomized to pomalidomide and dexamethasone. Time to first response was comparable for patients receiving elotuzumab plus pomalidomide and dexamethasone and pomalidomide and dexamethasone at 1.95 and 1.91 months, respectively. Median duration of response had not been reached among patients randomized to elotuzumab plus pomalidomide and dexamethasone at time of analysis. Overall survival, a secondary endpoint, although not mature at this time, showed a positive trend favoring elotuzumab plus pomalidomide and dexamethasone over pomalidomide and dexamethasone alone (HR = 0.62; 95% CI = 0.30–1.28).
Treatment-related grade 3–4 adverse events were comparable between elotuzumab plus pomalidomide and dexamethasone and pomalidomide and dexamethasone groups. Any-grade infections occurred in 65% of patients in both arms. Rates of the most commonly occurring grade 3–4 hematologic adverse events—neutropenia and anemia—were lower among patients receiving elotuzumab plus pomalidomide and dexamethasone (13% and 10%, respectively) than patients receiving pomalidomide and dexamethasone (27% and 20%), despite longer exposure within the elotuzumab plus pomalidomide and dexamethasone arm and similar dose intensity of pomalidomide between arms. Adverse events led to discontinuation in 18% of patients in the elotuzumab plus pomalidomide and dexamethasone arm, compared with 24% of patients in the pomalidomide and dexamethasone arm.
More About ELOQUENT-3
The phase II ELOQUENT-3 trial randomized 117 patients with relapsed/refractory multiple myeloma who received two or more prior therapies and were either refractory or relapsed and refractory to lenalidomide and a proteasome inhibitor. Patients were randomized 1:1 to receive either elotuzumab plus pomalidomide and dexamethasone (n = 60) or pomalidomide and dexamethasone (n = 57) in 28-day cycles until disease progression or unacceptable toxicity. Patients in both the elotuzumab plus pomalidomide and dexamethasone and pomalidomide and dexamethasone arms received 4 mg of pomalidomide for days 1–21 of each cycle, and the weekly equivalent of 40 mg or 20 mg dexamethasone for patients ≤ 75 years or > 75 years, respectively. In the elotuzumab plus pomalidomide and dexamethasone arm, elotuzumab was administered at the dose of 10 mg/kg intravenously weekly for the first 2 cycles and 20 mg/kg monthly starting from cycle 3.
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