ELOQUENT-3: Addition of Elotuzumab to Pomalidomide and Dexamethasone in Previously Treated Multiple Myeloma
As reported in The New England Journal of Medicine by Dimopoulos et al, the phase II ELOQUENT-3 trial has shown that the addition of elotuzumab (Empliciti) to pomalidomide (Pomalyst) and dexamethasone significantly prolonged progression-free survival in patients with relapsed and/or refractory multiple myeloma who previously received treatment with lenalidomide (Revlimid) and a proteasome inhibitor. The trial supported the recent approval of elotuzumab in combination with pomalidomide/dexamethasone in this setting.
Study Details
In the open-label trial, 117 patients from 43 sites in Europe, North America, Japan, and Australia were randomly assigned between March 2016 and April 2017 to receive elotuzumab, pomalidomide, and dexamethasone (n = 60) or pomalidomide and dexamethasone (n = 57). Treatment was given in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent.
Elotuzumab was given intravenously at 10 mg/kg on days 1, 8, 15, and 22 during cycles 1 and 2 and 20 mg/kg on day 1 of each cycle thereafter. All patients received oral pomalidomide at 4 mg/d on days 1 through 21 of each cycle. Patients received oral dexamethasone at 40 mg (patients aged ≤ 75 years) or 20 mg (patients aged > 75 years) per week, except on the days of elotuzumab administration, when patients in the elotuzumab group received dexamethasone both orally (28 mg in patients aged ≤ 75 years or 8 mg in patients aged > 75 years) and intravenously (8 mg).
Randomization was stratified by number of previous lines of therapy (2 or 3 vs ≥ 4) and International Staging System disease stage at enrollment. The primary endpoint was investigator-assessed progression-free survival.
For the elotuzumab vs control groups: median age was 69 vs 66 years (63% vs 61% ≥ 65 years, 22% vs 21% ≥ 75 years); 53% vs 61% were male; 88% vs 88% had stage I or II disease; 60% vs 63% had 2 or 3 and 40% vs 37% had ≥ 4 prior lines of therapy; 90% vs 84% were refractory to lenalidomide and 8% vs 12% had relapse and were refractory to lenalidomide; 78% vs 82% were refractory to a proteasome inhibitor and 22% vs 14% had relapse and were refractory to a proteasome inhibitor; and 68% vs 72% were refractory to both lenalidomide and a proteasome inhibitor.
Progression-Free Survival
Minimum follow-up at database lock in February 2018 was 9.1 months. Median progression-free survival was 10.3 months in the elotuzumab group vs 4.7 months in the control group (hazard ratio [HR] = 0.54, P = .008). The benefit of elotuzumab was consistent across patient subgroups, including among patients with 2 to 3 prior lines of therapy (HR = 0.55, 95% confidence interval [CI]= 0.31–0.98), those with ≥ 4 prior lines of therapy (HR = 0.51, 95% CI = 0.24–1.08), those with disease stage I or II (HR = 0.54, 95% CI = 0.33–0.90), those with stage III disease (HR = 0.52, 95% CI = 0.16–1.69), and those with disease refractory to both lenalidomide and a proteasome inhibitor (HR = 0.56, 95% CI = 0.33–0.97). On independent review committee assessment, median progression-free survival was 10.3 months vs 4.7 months (HR = 0.51, 95% CI = 0.32–0.82).
The overall response rate on investigator assessment was 53% in the elotuzumab group vs 26% in the control group (odds ratio [OR] = 3.25, 95% CI = 1.49–7.11), with 20% vs 9% of patients having a very good partial response or better. Median time to response was 2.0 vs 1.9 months. Median duration of response was not reached vs 8.3 months. The overall response rate on independent review committee assessment was 58% vs 25% (OR = 4.62, 95% CI = 2.05–10.43).
At the time of analysis, overall survival data were immature; 22% of the elotuzumab group vs 32% of the control group had died (HR = 0.62, 95% CI = 0.30–1.28).
Adverse Events
Grade 3 or 4 adverse events were reported in 57% of the elotuzumab group vs 60% in the control group, with the most common in the elotuzumab group being neutropenia (13% vs 27%), anemia (10% vs 20%), hyperglycemia (8% vs 7%), thrombocytopenia (8% vs 5%), and lymphopenia (8% vs 2%). Infections of any grade were reported in 65% of both groups, with grade 3 or 4 infections occurring in 13% vs 22%. Serious adverse events occurred in 53% vs 55% of patients.
Adverse events led to discontinuation of treatment in 18% vs 24% of patients, with causes including infection in 7% vs 5%. Infusion reactions occurred in 5% of the elotuzumab group. No deaths in either group were considered to be drug-related.
The investigators concluded, “Among patients with multiple myeloma in whom treatment with lenalidomide and a proteasome inhibitor had failed, the risk of progression or death was significantly lower among those who received elotuzumab plus pomalidomide and dexamethasone than among those who received pomalidomide plus dexamethasone alone.”
The study was funded by Bristol-Myers Squibb and AbbVie Biotherapeutics.
Disclosure: See study authors’ full disclosures at nejm.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
