Phase 3 ELOQUENT-2 Study: Extended 4-Year Follow-Up of Elotuzumab plus Lenalidomide and Dexamethasone versus Lenalidomide and Dexamethasone in RRMM
Elotuzumab, an immunostimulatory monoclonal antibody, has a dual mechanism of action, directly activating natural killer cells and tagging myeloma cells for recognition and death through antibody-dependent, cell-mediated cytotoxicity. In a 3-year follow-up, the ELOQUENT-2 study showed a sustained 27% risk reduction in disease progression/death, as well as overall survival (OS), in patients receiving the elotuzumab plus lenalidomide/dexamethasone (ELd) combination versus lenalidomide/dexamethasone (Ld) alone (Dimopoulos, et al. ASH 2015). This study reports the extended 4-year follow-up data of the ELOQUENT-2 study.
Patients with relapsed/refractory multiple myeloma (RRMM) were randomized 1:1 to receive either ELd or Ld in 28-day cycles until disease progression or unacceptable toxicity. The primary end points tested were progression-free survival (PFS) and overall response rate (ORR). OS was also studied as a secondary end point.
A total of 646 patients with RRMM were enrolled in this study; 321 were randomized to the ELd group and 325 patients to the Ld group. At study end, twice as many patients remained on therapy in the ELd group versus the Ld group (17% vs 9%, respectively). The major cause of treatment discontinuation was disease progression in 54% of patients in both treatment arms.
The ORR was 79% in the ELd group versus 66% in the Ld group. PFS was 19.4 months in the ELd group compared with 14.9 months in the Ld group. Likewise, there was a sustained OS benefit with ELd versus Ld (4-year OS: 48.3 months vs 39.6 months). At 4-year follow-up, the ELd group showed a 29% risk reduction of disease progression/death versus the Ld group (hazard ratio, 0.71; 95% confidence interval, 0.59-0.86).
The rates of adverse events were similar for the 2 treatment arms, and were consistent with prior 2- and 3-year follow-up data.
ELd consistently met its efficacy end points at the 4-year follow-up—the longest median follow-up reported for an immuno-oncology agent in MM. ELd showed durable, clinically relevant improvement in PFS, with a 29% risk reduction of disease progression or death. No new safety signals were seen at 4 years of follow-up.
Lonial S, et al. ASCO Abstract 8028.