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

Abstract 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. Disclosures Dimopoulos: Genesis: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Novartis: Honoraria; Janssen: Honoraria; Onyx: Honoraria; Janssen-Cilag: Honoraria. Off Label Use: Elotuzumab is an investigational agent being studied for the treatment of multiple myeloma. . Lonial:Novartis: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Onyx: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. White:Millennium: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Honoraria. Moreau:Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Palumbo:Array BioPharma: Honoraria; Janssen-Cilag: Consultancy, Honoraria; Sanofi-Aventis: Honoraria; Genmab A/S: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Millennium: Consultancy, Honoraria; Onyx: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. San Miguel:Novartis: Honoraria; Sanofi-Aventis: Honoraria; Janssen-Cilag: Honoraria; Celgene: Honoraria; Onyx: Honoraria; Bristol-Myers Squibb: Honoraria; Millennium: Honoraria. Shpilberg:Millennium Takeda: Consultancy; Gilead: Consultancy. Spicka:Janssen-Cilag: Consultancy; Celgene: Consultancy, Research Funding; Amgen: Consultancy; Bristol-Myers Squibb: Consultancy. Mateos:Onyx: Consultancy; Janssen-Cilag: Consultancy, Honoraria; Takeda: Consultancy; Celgene: Consultancy, Honoraria. Reece:Amgen: Honoraria; Novartis: Honoraria, Research Funding; Otsuka: Research Funding; Janssen-Cilag: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Lundbeck: Honoraria; Millennium Takeda: Research Funding; Bristol-Myers Squibb: Research Funding; Onyx: Consultancy; Merck: Research Funding. Beksac:Novartis: Consultancy; Takeda: Consultancy, Honoraria; Amgen: Honoraria, Speakers Bureau; Janssen-Cilag: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy. Bleickhardt:Bristol-Myers Squibb: Employment. Poulart:Bristol-Myers Squibb: Employment. Katz:Bristol-Myers Squibb: Employment. Singhal:Abbvie: Employment. Richardson:Celgene: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Millennium Takeda: Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Membership on an entity's Board of Directors or advisory committees.

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