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

Introduction: Elotuzumab is an immunostimulatory monoclonal antibody (mAb) that recognizes Signaling Lymphocytic Activation Molecule F7 (SLAMF7), a protein highly expressed by myeloma and natural killer cells. Elotuzumab has a dual mechanism of action, directly activating natural killer cells and initiating antibody-dependent cell-mediated cytotoxicity targeted against myeloma cells, with minimal effect on normal tissues. In the 2-year progression-free survival (PFS) interim analysis of ELOQUENT-2, a Phase 3 study (NCT01239797) comparing elotuzumab plus lenalidomide/dexamethasone (ELd) with lenalidomide/dexamethasone (Ld), ELd resulted in a significant 30% reduction in the risk of disease progression or death vs Ld (hazard ratio 0.70 [95% CI 0.57, 0.85]; p=0.0004). Overall response rate (ORR) was 79% (95% CI 74, 83) in the ELd arm vs 66% (95% CI 60, 71) in the Ld arm (p=0.0002). Furthermore, the addition of elotuzumab to Ld was well tolerated, with minimal added toxicity.¹ Elotuzumab's immunotherapeutic effect induces effective therapeutic outcomes and represents an important approach to treating multiple myeloma (MM). Here we present extended 3-year follow-up data.

Methods: As previously described,¹ patients (pts) with relapsed/refractory MM (RRMM) and 1-3 prior therapies were randomized 1:1 to ELd or Ld in 28-day cycles until disease progression or unacceptable toxicity. Primary endpoints were PFS and ORR. Secondary and other endpoints included overall survival (OS) and health-related quality of life. Post hoc analyses assessed Worst Pain using the Brief Pain Inventory-Short Form (BPI-SF); data were collected at screening, on Day 1 of each 28-day cycle, and at the end of treatment. Sustained improvement in pain was defined by a decrease of ≥3 points for ≥2 consecutive treatment cycles.

Results: In total, 646 RRMM pts were randomized (321 to ELd, 325 to Ld). Baseline demographic factors included: median age 66 years (20% ≥75 years old); 32% of pts had del17p and 10% had t(4;14); median prior number of therapies was 2; and 35% of pts were refractory to their last therapy. At data cut-off (16 May 2015), 29% of pts treated with ELd vs 15% of pts treated with Ld remained on study therapy; discontinuation was mainly due to disease progression (46% in ELd arm, 51% in Ld arm). Grade 3-4 adverse events in ≥15% of pts included lymphopenia (78% in ELd arm, 49% in Ld arm), neutropenia (35% in ELd arm, 44% in Ld arm), anemia (20% in ELd arm, 21% in Ld arm), and thrombocytopenia (21% in ELd arm, 20% in Ld arm). Infections (any grade) occurred in 83% of pts in the ELd arm and 75% in the Ld arm. Exposure-adjusted infection rates (incidence rate/100 person-years of exposure) were 196 and 193 in the ELd and Ld arms, respectively. Infusion reactions (mostly Grade 1-2) occurred in 11% of pts treated with ELd. In total, there were 263 deaths during treatment follow-up (123 [47%] in ELd arm, 140 [53%] in Ld arm); 62% of the required 427 deaths for the OS final analysis. With regard to patient-reported pain (BPI-SF), sustained improvement in Worst Pain was observed in pts with ORR, with more pts demonstrating sustained improvement in the ELd arm (n=74) vs the Ld arm (n=56). 3-year PFS and the interim analysis of OS will be presented.

Conclusions: Elotuzumab is the first immunostimulatory mAb for the treatment of MM to demonstrate a statistically significant and clinically relevant improvement in efficacy with minimal added toxicity.¹ The addition of elotuzumab to Ld led to an effective and durable benefit, representing a novel approach to treating MM. The updated safety and tolerability data reported were consistent with previous findings, confirming that there are minimal incremental toxicities associated with the addition of elotuzumab. A greater proportion of ELd pts vs Ld pts with an ORR had improvement in BPI-SF Worst Pain. Three-year PFS data and the interim analysis of OS will be presented, providing insight into the long-term benefits of ELd therapy.

Reference:

1. Lonial S et al. N Engl J Med 2015; Jun 2 [Epub ahead of print].

Study funding: Study funded by Bristol-Myers Squibb and AbbVie Biotherapeutics. Writing assistance was provided by S Addison, PhD, at Caudex and funded by Bristol-Myers Squibb.