ELOQUENT-2 trial to assess efficacy of elotuzumab therapy for RRMM

In August 2015, Sagar Lonial, Meletios D. Dimopoulos and colleagues, reported results from the open-label, multi-center ELOQUENT-2 trial in The New England Journal of Medicine. This was the pivotal phase III study leading to approval of elotuzumab for the treatment of patients with Relapsed and/or Refractory Multiple Myeloma (RRMM). They enrolled 646 patients (between June 2011 and November 2012 at 168 sites globally) who had received one to three prior therapies, and who had relapsed following their most recent therapy. Patients were randomly assigned into two treatment groups, receiving a combined regimen of lenalidomide plus dexamethasone plus elotuzumab (321 patients) or lenalidomide plus dexamethasone alone (control, 325 patients). Primary endpoints were Progression Free Survival (PFS) and Overall Response Rate (ORR).

Treatment:

• Treatment was administered in 28-day cycles
• Intravenous elotuzumab (10 mg/kg of body weight) was administered on days 1, 8, 15 and 22, during cycle 1 and 2, then on day 1 and 15 in cycle 3
• Oral lenalidomide (25 mg per day) was administered from day 1 –day 21 of each cycle
• Oral dexamethasone (40 mg) was administered during the week without elotuzumab and intravenously at a dose of 8 mg, plus 28 mg orally on the day of elotuzumab treatment (days 1, 8, 15 and 21)
• Control group received the same regimen, minus elotuzumab
• Pre-medication (H1 blocker, H2 blocker, and acetaminophen) were administered prior to elotuzumab infusion
• Only 10% of patients that received previous lenalidomide treatment were allowed to enrol

Key Findings:

Data is given as elotuzumab vs control:

• Median follow-up = 24.5 months
• Pts still receiving treatment at the cut-off date for interim analysis = 35% vs 20%
• Rate of PFS: 1 year: 68% vs 57%; 2 years: 41% vs 27%
• Median PFS: 19.4 months (95% CI, 16.6 to 22.2) vs 14.9 months (95% CI, 12.1 to 17.2)
• HR = 0.70; 95% CI, 0.57 to 0.85; P<0.001
• Safety dataset: elotuzumab = 318 pts and control = 317 pts
• ITT population: 32% relative reduction in the risk of disease progression in the elotuzumab group (HR, 0.68; 95% CI, 0.56-0.83)
• ORR: 79% (95% CI, 74-83) vs 66% (95% CI, 60-71) (odds ratio for elotuzumab vs control = 1.9 (95% CI, 0.44 to 0.70); P<0.001)
• Durable responses: 21 months (95% CI, 18 to 27) vs 17 months (95% CI, 15 to 19)
• Grade 3 or 4 AEs were: lymphocytopenia, neutropenia, fatigue, and pneumonia
• Infusion reactions in elotuzumab group = 33 pts (10%); grade 1 or 2 in 29 patients
• Pts continued treatment until the development of unacceptable toxicity or due to disease progression

Patients receiving elotuzumab, on a background of the combined regimen of lenalidomide plus dexamethasone, had a 30% reduction in the risk of disease progression or death. This trial was pivotal in driving the approval of elotuzumab by the US Food and Drug Administration (US FDA) (in November 2015) for use in combination with two other therapies, to treat patients with MM who have received one to three prior medications. Elotuzumab was also approved by the European Medicines Agency (EMA) (in January 2016) for the same indication. The full article can be found here.