The addition of elotuzumab to lenalidomide and dexamethasone did not show a statistically significant improvement in progression-free survival compared with lenalidomide/dexamethasone alone in patients with newly diagnosed, previously untreated, transplant-ineligible multiple myeloma.
Meletios A. Dimopoulos, MD
The addition of elotuzumab (Empliciti) to lenalidomide (Revlimid) and dexamethasone did not show a statistically significant improvement in progression-free survival (PFS) compared with lenalidomide/dexamethasone alone in patients with newly diagnosed, previously untreated, transplant-ineligible multiple myeloma, missing the primary endpoint of the phase III ELOQUENT-1 trial (NCT01335399).1
The final analysis of the study also showed that the safety profile of the triplet regimen was consistent with known tolerability profiles from prior studies. Full findings are expected to be presented at an upcoming medical meeting, Bristol Myers Squibb (BMS), which co-develops elotuzumab with AbbVie, stated in a press release.
"Multiple myeloma is an aggressive disease characterized by relapse and the likelihood to be refractory to several therapies," Meletios A. Dimopoulos, MD, professor and chairman of the Department of Clinical Therapeutics at Kapodistrian University of Athens School of Medicine, stated in a press release. "While the elotuzumab, lenalidomide and dexamethasone combination was unable to show a benefit in patients with newly diagnosed multiple myeloma at this time, it remains an important treatment option in the relapsed/refractory setting."
In the open-label, phase III ELOQUENT-1 trial, investigators evaluated the combination of lenalidomide/dexamethasone with or without elotuzumab in patients with newly diagnosed, previously untreated myeloma. Lenalidomide was given orally at 25 mg once daily on days 1 through 21 every 28 days, while oral dexamethasone was administered weekly at 40 mg on days 1, 8, 15, and 22 in 28-day cycles. In the experimental arm, elotuzumab was given intravenously at 10 mg/kg weekly on days 1, 8, 15, 22 in the first 2 cycles and on days 1 and 15 of cycles 3 to 18, followed by 20 mg/kg on day 1 of cycle 19 forward. Patients in both arms received treatment continuously until disease progression.
To be eligible for enrollment, patients must have had newly diagnosed, symptomatic multiple myeloma and did not receive any prior systemic therapy, had measurable disease, and were not candidates for high-dose therapy plus stem cell transplant. Patients with non-secretory or oligo-secretory or free light-chain only myeloma, had smoldering myeloma, had monoclonal gammopathy of undetermined significance, active plasma cell leukemia, or known HIV infection or active hepatitis A, B, or C, could not enroll on the study.
The primary endpoint was PFS; secondary endpoints were objective response and overall survival.
"While we are disappointed that the ELOQUENT-1 trial did not meet its primary endpoint in these previously untreated, transplant-ineligible patients, the Empliciti, Revlimid and dexamethasone combination remains a standard treatment for patients with relapsed/refractory multiple myeloma, providing the potential for improved survival in this population of patients who are in need of additional treatment options," Noah Berkowitz, MD, PhD, senior vice president, Global Clinical Development, Hematology, BMS, stated in the press release.
Elotuzumab was first approved by the FDA in November 2015 for use in combination with lenalidomide and dexamethasone for patients with multiple myeloma following the failure of 1 to 3 prior therapies.
The decision was based on data from the phase III ELOQUENT-2 trial, in which the 3-drug elotuzumab combination reduced the risk of disease progression by 30% versus lenalidomide/dexamethasone alone.2
In November 2018, the FDA approved elotuzumab for use in combination with pomalidomide (Pomalyst) and low-dose dexamethasone for the treatment of patients with relapsed/refractory multiple myeloma following ≥2 prior therapies, including lenalidomide and a proteasome inhibitor.
The approval was based on findings from the phase II ELOQUENT-3 trial, in which the addition of elotuzumab to pomalidomide/dexamethasone reduced the risk of disease progression or death by 46% compared with pomalidomide and dexamethasone alone for patients with relapsed/refractory multiple myeloma.3
Specifically, preliminary findings showed that the median PFS was 10.3 months (95% CI, 5.6—not estimable [NE]) with the elotuzumab combination versus 4.7 months (95% CI, 2.8-7.2) with pomalidomide plus dexamethasone (HR, 0.54; 95% CI, 0.34-0.86; P = .008). The PFS benefit associated with the elotuzumab triplet was similar, regardless of whether patients had received 2 to 3 prior lines of treatment (HR, 0.55; 95% CI, 0.31-0.98), or ≥4 lines of treatment (HR, 0.51; 95% CI, 0.24-1.08).
In extended follow-up at ≥18.3 months of a non-prespecified analysis—to provide a descriptive assessment of OS-results showed that patients treated with the elotuzumab regimen experienced sustained and clinically relevant PFS and OS benefits versus those on the pomalidomide/dexamethasone arm.4
In this analysis, the median OS was not reached with elotuzumab (95% CI, 24.9—NE) compared with 17.4 months (95% CI, 13.8–NE) with pomalidomide/dexamethasone. The 18-month OS rates were 68% and 49% for the elotuzumab regimen and pomalidomide/dexamethasone alone, respectively.