ELOQUENT-2: A phase III, randomized, open-label study of lenalidomide (Len)/dexamethasone (dex) with/without elotuzumab (Elo) in patients (pts) with relapsed/refractory multiple myeloma (RRMM).

8508 Background: Elo, a monoclonal antibody (mAb) targeting Signaling Lymphocytic Activation Molecule F7 (SLAMF7), kills myeloma cells with minimal effect on normal tissue. Elo showed encouraging activity with Len/dex (Ld) in a phase Ib/II study in pts with RRMM. This phase III study (NCT01239797) compared efficacy and safety of Elo/Len/dex (ELd) vs Ld. Methods: Pts with RRMM, 1–3 prior therapies (not Len-refractory), were randomized 1:1 to ELd or Ld in 28-day cycles to disease progression/unacceptable toxicity: Elo (10 mg/kg intravenously) weekly cycles 1+2 then biweekly; Len (25 mg) D1–21; dex weekly (40 mg or [Elo wks] 28 mg oral + 8 mg intravenous). Response/progression was assessed by independent review committee by EBMT criteria. Primary endpoints were progression-free survival (PFS) and overall response rate (ORR). Results of an interim analysis are reported. Results: Six hundred and forty-six pts were randomized (321 ELd, 325 Ld; median age 66; del(17p) 32%; t[4;14] 9%; refractory to last therapy 35%). Median (range) prior therapies: 2 (1–4), including bortezomib 70%, thalidomide 48%, Len 6%. At data cut-off (4 November 2014), 35% (ELd) and 21% (Ld) of pts remained on therapy; discontinuation was mainly for disease progression (42% ELd, 47% Ld). Median follow-up was 24 months; median (95% CI) PFS: ELd 19.4 (16.6, 22.2) months, Ld 14.9 (12.1, 17.2) months (HR [95% CI] 0.70 [0.57, 0.85]; p = 0.0004). 1-year PFS was 68% ELd, 57% Ld; 2-year PFS: 41% ELd, 27% Ld. PFS benefit with ELd was consistent across key subgroups. ORR (95% CI) was 79% (74, 83) ELd, 66% (60, 71) Ld (p = 0.0002). G3–4 adverse events ≥ 15% (ELd vs Ld) were neutropenia (25%, 33%); anemia (15%, 16%). Exposure-adjusted infection rate was the same in both arms (incidence rate/100 person-years of exposure, 197). Infusion reactions (IRs) occurred in 10% of pts with ELd (mostly G1–2). There were 210 deaths (94 ELd, 116 Ld). Conclusions: A clinically relevant 30% reduction in risk of progression or death was seen with ELd vs Ld. More pts remain on ELd vs Ld and follow-up for long-term outcomes, including survival, is ongoing. IRs were manageable. Elo, a mAb with a novel immunotherapeutic mechanism of action, showed improved PFS, with minimal added toxicity in combination with Ld vs Ld alone, in pts with multiple myeloma. Clinical trial information: NCT01239797.