The triplet regimen of elotuzumab plus pomalidomide and dexamethasone led to a 46% reduction in the risk of death compared with pomalidomide/dexamethasone alone in patients with relapsed/refractory multiple myeloma, according to updated findings of the phase II ELOQUENT-3 trial.
Meletios A. Dimopoulos, MD
Meletios A. Dimopoulos, MD
The triplet regimen of elotuzumab (Empliciti) plus pomalidomide (Pomalyst) and dexamethasone led to a 46% reduction in the risk of death compared with pomalidomide/dexamethasone alone in patients with relapsed/refractory multiple myeloma, according to updated findings of the phase II ELOQUENT-3 trial presented at the 2019 European Hematology Association Congress.1,2
In extended follow-up at ≥18.3 months of a non-prespecified analysis to provide a descriptive assessment of overall survival (OS), results showed that patients treated with the elotuzumab regimen experienced sustained and clinically relevant progression-free survival (PFS) and OS benefits (HR, 0.54; 95% CI, 0.30-0.96) versus those on the pomalidomide/dexamethasone arm.
“Multiple myeloma is a disease characterized by relapse, making it all the more important to have effective options available for patients after initial treatments. With 18 months of follow-up from the ELOQUENT-3 trial, we continue to see meaningful improvements across key endpoints with [elotuzumab/pomalidomide/dexamethasone] versus [pomalidomide/dexamethasone] alone, including a positive trend in overall survival,” said lead study author Meletios A. Dimopoulos, MD, professor and chairman of the Department of Clinical Therapeutics at Kapodistrian University of Athens School of Medicine. These data point to the potential for this combination to become a new standard of care for patients with multiple myeloma that returned after or did not respond to prior therapies, including lenalidomide (Revlimid) and a proteasome inhibitor.”
Based on primary findings of the ELOQUENT-3 trial, the FDA approved elotuzumab for use in combination with pomalidomide and low-dose dexamethasone for the treatment of patients with relapsed/refractory multiple myeloma following ≥2 prior therapies, including lenalidomide and a proteasome inhibitor.
ELOQUENT-3 enrolled 117 patients with relapsed/refractory multiple myeloma who were randomized to receive the elotuzumab triplet (n = 60) or pomalidomide/dexamethasone alone (n = 57). Elotuzumab was administered at 10 mg/kg intravenously each week during cycles 1 and 2 and at 20 mg/kg every 4 weeks thereafter. Pomalidomide was given at 4 mg orally on days 1 to 21 of each cycle plus weekly dexamethasone at 40 mg for patients ≤75 years of age or 20 mg for those >75 years.
Patients who were eligible for enrollment had received ≥2 prior lines of therapy, including lenalidomide and a proteasome inhibitor; patients who had prior pomalidomide were excluded from the study. The median age of patients was 67 years and they had received a median of 3 prior treatments (range, 2-8). Prior treatments included bortezomib (Velcade; 100%), lenalidomide (99%), carfilzomib (Kyprolis; 21%), ixazomib (Ninalro; 6%), and daratumumab (Darzalex; 3%). Fifty-five percent had undergone stem cell transplantation and most patients were refractory to lenalidomide (87%), a proteasome inhibitor (80%), or both (70%).
The primary objective of the study was investigator-assessed PFS, and secondary endpoints included ORR and OS.
At the time of the updated analysis, additional results showed that the median OS was not reached with elotuzumab (95% CI, 24.9—not estimable [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.
Moreover, 18-month PFS rates were 34% among patients randomized to the elotuzumab arm compared with 11% with pomalidomide/dexamethasone.
Regarding safety, the tolerability with elotuzumab triplet was similar to the primary ELOQUENT-3 analysis and for prior data with elotuzumab- and pomalidomide-containing regimens. The most common grade 3/4 AEs were infections (22% with elotuzumab vs 24% with pomalidomide/dexamethasone), neutropenia (13% vs 29%, respectively), anemia (10% vs 22%), thrombocytopenia (10% vs 7%) and hyperglycemia (8% vs 11%). Grade 5 all-cause AEs occurred in 7 patients (12%) who received the elotuzumab regimen and in 9 patients (16%) who received pomalidomide/dexamethasone.
“The extended follow-up results from ELOQUENT-3 reinforce the [elotuzumab/pomalidomide/dexamethasone] combination’s sustained efficacy and favorable safety profile in patients with relapsed or refractory multiple myeloma,” said Fouad Namouni, MD, head, Oncology Development, Bristol-Myers Squibb, which jointly develops elotuzumab with Abbvie. “These data, along with our overall presence at EHA, underscore our commitment to leading innovative research in hematology and developing therapies that can improve long-term survival for patients with different types of blood cancer.”
At the prior February 21, 2018, database lock, and a 9.1-month median follow-up, 40% of patients on the elotuzumab combination remained on treatment compared with 20% in the control arm. The prior data showed that the median PFS was 10.3 months (95% CI, 5.6—not estimable) with the elotuzumab triplet versus 4.7 months (95% CI, 2.8-7.2) with pomalidomide/dexamethasone (HR, 0.54; 95% CI, 0.34-0.86; P = .0078).3 The PFS benefit associated with the elotuzumab arm was similar, despite if patients received 2 to 3 prior lines of therapy (HR, 0.55; 95% CI, 0.31-0.98), or ≥4 lines (HR, 0.51; CI 95%, 0.24-1.08).
Moreover, the initial objective response rate (ORR) was 53% (95% CI, 40%-66%) with elotuzumab compared with 26% (95% CI, 16%-40%) in the pomalidomide/dexamethasone group (odds ratio, 3.25; 95% CI, 1.49-7.11; P = .0029). The rate of very good partial response or better was 20% versus 9%, with and without elotuzumab, respectively.
Elotuzumab was initially approved by the FDA in November 2015 for use in combination with lenalidomide (Revlimid) and dexamethasone for the treatment of patients with multiple myeloma who previously received 1 to 3 therapies.