Extended 5-y follow-up (FU) of phase 3 ELOQUENT-2 study of elotuzumab + lenalidomide/dexamethasone (ELd) vs Ld in relapsed/refractory multiple myeloma (RRMM).

8040 Background: The immunostimulatory monoclonal antibody elotuzumab exhibits a dual mechanism of action, directly activating natural killer cells and mediating myeloma cell death via antibody-dependent cell-mediated cytotoxicity. In ELOQUENT-2 (NCT01239797), ELd showed sustained reduction in risk of disease progression or death at 2- (30%), 3- (27%), and 4-y (29%) FU vs Ld, and a favorable trend in overall survival (final analysis at 427 deaths). Here we present progression-free survival (PFS) data at 5 y, a milestone timepoint in cancer survival analyses. Methods: RRMM patients (pts) randomized 1:1 to ELd or Ld in 28-d cycles until disease progression/unacceptable toxicity. Coprimary endpoints: PFS and overall response rate (ORR) per independent review committee. Results: In all, 646 pts were randomized to ELd (n = 321) and Ld (n = 325). At database lock (Nov 29, 2017), 13% (ELd) vs 7% (Ld) of pts remained on treatment; discontinuation was mostly due to disease progression (55 vs 56%). At 5-y FU (minimum 60 mo), ELd showed 27% reduction in risk of progression or death vs Ld (HR 0.73, 95% CI 0.60–0.87) and relative improvement of 50% in PFS rate at 5 y (18 vs 12%). Pts with ≥very good partial response (ELd 36% vs Ld 30%) had the greatest reduction in risk of progression/death (HR 0.63, 95% CI 0.44–0.89). ORR was 79% (ELd) vs 66% (Ld). G3–4 AEs included blood and lymphatic system disorders (ELd vs Ld: 46 vs 46%), infections (35 vs 27%), vascular diseases (11 vs 8%), second primary malignancies (SPMs; 10 vs 6%), and cardiac disorders (5 vs 8%). Higher rate of any-grade infection (84 vs 75%) and SPMs (17 vs 11%) may reflect longer median duration of treatment with each agent of the ELd vs Ld regimens (E/L/d vs L/d: 17/17/17 vs 12/12 mo). Fewer deaths occurred with ELd than Ld (193 vs 208), mostly due to disease progression. Conclusions: Elotuzumab (+ Ld) has the longest median FU of an immuno-oncology agent in MM. At the milestone timepoint of 5 y, ELd showed sustained, durable clinically relevant improvement in PFS, a 27% reduction in the risk of progression or death, and a safety profile with minimal incremental AEs with ELd vs Ld. Study funding: BMS. Writing support: L Yee, Caudex, funded by BMS. Clinical trial information: NCT01239797.