FDA Approves Elotuzumab Plus Pomalidomide and Dexamethasone for Relapsed or Refractory Multiple Myeloma
On November 6, the U.S. Food and Drug Administration (FDA) approved elotuzumab (Empliciti) injection for intravenous use in combination with pomalidomide (Pomalyst) and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least two prior therapies, including lenalidomide (Revlimid) and a proteasome inhibitor.
In ELOQUENT-3, a randomized, open-label, phase II trial, elotuzumab plus pomalidomide and dexamethasone demonstrated benefit in patients with relapsed or refractory multiple myeloma, doubling both median progression-free survival and overall response rate vs pomalidomide and dexamethasone.
Following Priority Review by the FDA, elotuzumab plus pomalidomide and dexamethasone is the first triplet combination to be approved based on a randomized clinical trial using pomalidomide and dexamethasone as a comparator.
About ELOQUENT-3
ELOQUENT-3 was a randomized, open-label phase II study evaluating the addition of elotuzumab to pomalidomide and dexamethasone vs pomalidomide and dexamethasone in 117 patients with 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 randomly assigned 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.
The approved dose of elotuzumab when used in combination with pomalidomide and dexamethasone is 10 mg/kg administered intravenously every week for the first two 28-day cycles, followed by 20 mg/kg every 4 weeks until disease progression or unacceptable toxicity.
The primary efficacy outcome measure of the trial was progression-free survival as determined by the investigator. The secondary efficacy outcome measure of overall response rate included complete, stringent-complete, very good partial, and partial response rates as determined by investigator assessment, based on the International Myeloma Working Group criteria.
Results from the ELOQUENT-3 trial, which were presented at the 23rd Congress of the European Hematology Association in June 2018 (Abstract LB2606) in June 2018, include:
- Progression-free survival: Elotuzumab plus pomalidomide and dexamethasone reduced the risk of disease progression by 46% (hazard ratio [HR] = 0.54; 95% confidence interval [CI] = 0.34–0.86, P = .0078), demonstrating a median progression-free survival of 10.25 months (95% CI = 5.59–nonestimable) vs 4.67 months (95% CI = 2.83–7.16) for pomalidomide and dexamethasone alone after a minimum follow-up of 9.1 months.
- Overall response rate: Response rates doubled in patients receiving elotuzumab plus pomalidomide and dexamethasone (53.3%; n = 32 of 60 [95% CI = 40.0–66.3]) compared with patients receiving pomalidomide and dexamethasone alone (26.3%; n = 15 of 57 [95% CI = 15.5–39.7]; P = .0029), with very good partial responses or better seen in 20% of patients treated with elotuzumab plus pomalidomide and dexamethasone (n = 12) and 8.8% of patients treated with pomalidomide and dexamethasone.
- Safety: Serious adverse reactions were reported in 22% of patients treated with elotuzumab plus pomalidomide and dexamethasone and in 15% of patients treated with pomalidomide and dexamethasone. Discontinuation of any component of the treatment regimen due to adverse reactions occurred in 5.0% of patients in the elotuzumab plus pomalidomide and dexamethasone arm, compared to 1.8% of patients in the control arm.
Elotuzumab with pomalidomide and dexamethasone is associated with warnings and precautions related to infusion reactions, infections, secondary primary malignancies, hepatotoxicity, interference with determination of complete response, pregnancy, and reproductive potential.
