Interim analysis of the ELOQUENT-2 trial, a randomized, open-label phase 3 study that evaluated the safety and efficacy of combination therapy with the anti–Signaling Lymphocytic Activation Molecule F7 (SLAMF7) monoclonal antibody elotuzumab plus lenalidomide/dexamethasone (ELd) versus lenalidomide/dexamethasone (Ld) in patients with relapsed/refractory multiple myeloma (MM), had previously demonstrated significant improvements in progression-free survival (PFS) and overall response rate1; the extended 3-year follow-up results of this trial were reported by Dimopoulos and colleagues.2 A total of 646 patients with relapsed/refractory MM were randomized to receive ELd (n = 321) or Ld (n = 325). Del(17p) was observed in 32% of patients in each arm, and refractoriness to the most recent line of therapy was observed in 35% of patients in each arm. This 3-year follow-up analysis showed that ELd therapy was associated with a significant prolongation of PFS compared with Ld therapy (26% vs 18%; hazard ratio, 0.70; P = .0004). Consistently, ELd therapy resulted in a significantly higher overall response rate (79% vs 66%; P = .0002) compared with Ld therapy. Consistent improvement in PFS and overall survival was observed with ELd versus Ld across all predefined subgroups, including those with unfavorable cytogenetics. Grade 3/4 adverse events in the ELd-treated and Ld-treated cohorts included lymphopenia (78% vs 49%), neutropenia (26% vs 33%), anemia (15% vs 16%), and thrombocytopenia (21% vs 20%). High rates of infections (any grade) were reported in both arms (83% vs 75%); exposure-adjusted infection rates were found to be comparable (196 vs 193). Post hoc analyses assessing patient-reported worst pain found that responding patients achieved sustained worst pain improvements and that a higher proportion of patients in the ELd cohort achieved pain improvement compared with control (74 vs 56 patients). Based on these updated 3-year efficacy and safety results of the ELOQUENT-2 study, the authors concluded that incorporation of elotuzumab into the Ld backbone yields sustained improvements in efficacy outcomes without aggravating toxicities. Based largely on the strength of these data, elotuzumab in combination with lenalidomide and dexamethasone was approved on November 30, 2015, by the US Food and Drug Administration for patients with MM who have received 1 to 3 prior therapies.
- Lonial S, et al. N Engl J Med. 2015;373:621-631.
- Dimopoulos M, et al. ASH 2015. Abstract 28.