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

Konference: 2015 57th ASH Annual Meeting - účast ČR

Téma: 653. Myeloma: Therapy, excluding Transplantation: Advances in Newly Diagnosed and Relapsed Myeloma

Číslo abstraktu: 28

Autoři: Meletios Athanasios Dimopoulos, MD; Prof. MD Sagar Lonial; Darrell J. White; Prof. MD Philippe Moreau; MD Antonio P. Palumbo; Prof. M.D. Jesús San Miguel, Ph.D.; MD Ofer Shpilberg, MPH; MD Kenneth C. Anderson; M.D. Sebastian Grosicki; Prof.MUDr. Ivan Špička, PhD; Adam Walter-Croneck; Hila Magen-Nativ; MD Maria-Victoria Mateos, PhD; prof. MD Andrew Belch; MD Donna E. Reece, FRCPC; prof. MD Meral Beksac; MD Eric Bleickhardt; Valeriet Poulart; Jessica Katz; Anil K. Singhal; MD Paul Gerard Guy Richardson

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.¹Elotuzumab’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: Janssen: Consultancy , Research Funding ;Onyx: Consultancy , Research Funding ; Novartis: Consultancy , Research Funding ; Bristol-Myers Squibb:Consultancy , Research Funding ; Celgene: Consultancy , Research Funding ; Millennium: 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 .