ELOQUENT-2 Update: A Phase 3, Randomized, Open-Label Study of Elotuzumab in Combination with Lenalidomide/Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma—3-Year Safety and Efficacy Follow-Up
Elotuzumab is a monoclonal antibody that specifically targets Signaling Lymphocytic Activation Molecule F7 (SLAMF7), a protein expressed on myeloma and natural killer cells, to induce immunostimulatory and cytotoxic effects. Interim analysis of the ELOQUENT-2 trial, a phase 3 study comparing elotuzumab plus lenalidomide/dexamethasone (ELd) with lenalidomide/dexamethasone (Ld), were previously reported and showed significant improvements in the primary end points of progression-free survival (PFS) and overall response rate (ORR).1 At ASH 2015, Dimopoulos and colleagues reported on the extended 3-year follow-up results of the ELOQUENT-2 study.2
In the trial, 646 patients with relapsed/refractory multiple myeloma (MM) and 1 to 3 prior therapies were randomized to receive ELd (n = 321) or Ld (n = 325) in 28-day cycles until disease progression or unacceptable toxicity. At the 3-year follow-up, a significant prolongation of PFS was reported with ELd therapy compared with Ld therapy, with a 27% reduction in the risk of disease progression (median PFS, 19.4 months vs 14.9 months; hazard ratio [HR], 0.73; P = .0014) and a relative PFS improvement of 44%. Prespecified interim overall survival (OS) analysis also showed a significant and sustained improvement with ELd treatment compared with standard (median OS, 43.7 months vs 39.6 months; HR, 0.77; P = .0257). In addition, a significantly higher ORR (79% vs 66%; P = .0002) was achieved with ELd therapy compared with Ld therapy. Treatment discontinuation was mainly due to disease progression in both arms (48% vs 51%); 9% of patients on the ELd and 14% of patients in the Ld arms discontinued due to adverse events (AEs). Common AEs of interest of any grade included gastrointestinal (GI) disorders (81% vs 68%), respiratory disorders (63% vs 53%), renal/urinary disorders (25% vs 18%), peripheral neuropathy (15% vs 9%), and hypertension (10% vs 7%). Grade 3/4 AEs included neutropenia (26% vs 33%), anemia (15% vs 16%), fatigue (9% vs 8%), and diarrhea (5% in both). Exposure-adjusted infection rates (incidence rate/100 person-years of exposure) were similar (198 vs 192). Infusion reactions of any grade occurred in 10% of patients, mostly in the first treatment cycle. Post hoc analyses assessing worst pain using the Brief Pain Inventory–Short Form found that responding patients achieved sustained improvements in worst pain (sustained pain improvement was defined by a decrease of ?3 points for ?2 consecutive treatment cycles). A higher proportion of patients in the ELd cohort achieved pain improvement compared with control (74 vs 56 patients). The updated 3-year efficacy and safety results of the ELOQUENT-2 study indicate that the addition of elotuzumab to Ld is associated with sustained improvements in efficacy outcomes without exacerbating toxicities, representing a novel treatment option for patients with MM.
- Lonial S, et al. N Engl J Med. 2015;373:621-631.
- Dimopoulos M, et al. ASH 2015. Abstract 28.