The combination of elotuzumab plus lenalidomide and dexamethasone did not demonstrate a statistically significant improvement in progression-free survival compared with lenalidomide and dexamethasone alone in newly diagnosed patients with multiple myeloma who are transplant ineligible, missing the primary end point of the phase III ELOQUENT-1 trial.<br />
Meletios A. Dimopoulos, MD
Meletios A. Dimopoulos, MD
The combination of elotuzumab (Empliciti) plus lenalidomide (Revlimid) and dexamethasone (ERd) did not demonstrate a statistically significant improvement in progression-free survival (PFS) compared with lenalidomide and dexamethasone alone in newly diagnosed patients with multiple myeloma who are transplant ineligible, missing the primary end point of the phase III ELOQUENT-1 trial (NCT01335399), Bristol Myers Squibb announced in a press release.
Following a full evaluation of ELOQUENT-1, the trial data will be presented at a future medical meeting. Thus far, the company, which is co-developing elotuzumab with AbbVie, has shared that the safety profile of ERd was consistent with previous reports.
“Multiple myeloma is an aggressive disease characterized by relapse and the likelihood to be refractory to several therapies,” investigator Meletios A. Dimopoulos, MD, professor and chairman of the Department of Clinical Therapeutics at Kapodistrian University of Athens School of Medicine, said in the 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.”
The secondary end points of the randomized, open-label trial included objective response rate (ORR) and overall survival (OS).
The randomized, open-label trial included approximately 750 patients. In the comparator arm, patients received oral lenalidomide, 25 mg, on days 1 through 21 and oral dexamethasone, 40 mg, on days 1, 8, 15, and 22, in 28-day cycles. In the experimental arm, elotuzumab was administered at 10 mg/kg intravenously on days 1, 8, 15, and 22 of the first 2 cycles followed by on days 1 and 15 of cycles 3 through 18 and 20 mg/kg on day 1 of cycle 19 and beyond. Dexamethasone was administered at 8 mg intravenous and 28 mg orally when given with elotuzumab.
To be eligible for ELOQUENT-1, patients could not have received any prior systemic anti-myeloma therapy, were required to have measurable disease, and could not be candidates for high-dose therapy plus stem cell transplantation (SCT) because of age (≥65 years) or comorbid conditions. The study excluded patients with non-secretory, oligo-secretory, or free light-chain only myeloma; smoldering multiple myeloma; Monoclonal Gammopathy of Undetermined Significance; active plasma cell leukemia; and known immunodeficiency virus, infection, or active hepatitis A, B, or C.
“While we are disappointed that the ELOQUENT-1 trial did not meet its primary end point 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,” said Noah Berkowitz, MD, PhD, senior vice president, Global Clinical Development, Hematology, Bristol Myers Squibb.
Although ELOQUENT-1 did not show promise in terms of PFS, a phase III study (ELOQUENT-2, NCT01239797), met its primary efficacy end points of PFS, ORR, and its secondary end point OS, according to data published inCancerin 2018.2Based on ELOQUENT-2, another phase III study was launched, and quality-of-life results were announced at the 2019 American Society of Hematology (ASH) Annual Meeting.3In ELOQUENT-3, lenalidomide is replaced by pomalidomide (Pomalyst) and the regimen did not impair health-related quality of life in the study subjects. The triplet regimen from the ELOQUENT-3 trial was approved by the FDA in November 2018 for use in the relapsed/refractory setting for patients who have received 2 or more prior therapies, including lenalidomide and a proteasome inhibitor.
The differences in results between these 3 studies may suggest that the combination of a monoclonal antibody, chemotherapy, and a corticosteroid serves better in the relapsed/refractory setting than the newly diagnosed, previously untreated setting for patients with multiple myeloma.