ELOTUZUMAB PLUS POMALIDOMIDE AND DEXAMETHASONE FOR RELAPSED/REFRACTORY MULTIPLE MYELOMA: EFFICACY RESULTS AFTER ADDITIONAL FOLLOW-UP OF THE PHASE 2, RANDOMIZED ELOQUENT-3 STUDY
Author(s): ,
Meletios Dimopoulos
Affiliations:
National and Kapodistrian University of Athens,Athens,Greece
,
Dominik Dytfeld
Affiliations:
Karol Marcinkowski University of Medical Sciences,Poznan,Poland
,
Sebastian Grosicki
Affiliations:
Silesian Medical University,Katowice,Poland
,
Philippe Moreau
Affiliations:
University Hospital,Nantes,France
,
Naoki Takezako
Affiliations:
National Hospital Organization Disaster Medical Center,Tokyo,Japan
,
Mitsuo Hori
Affiliations:
Ibaraki Prefectural Central Hospital,Kasama,Japan
,
Xavier Leleu
Affiliations:
Centre Hospitalier Universitaire de Poitiers - La Milétrie,Poitiers,France
,
Richard LeBlanc
Affiliations:
Hôpital Maisonneuve-Rosemont, University of Montreal,Montreal,Canada
,
Kenshi Suzuki
Affiliations:
Japanese Red Cross Medical Center,Tokyo,Japan
,
Marc S. Raab
Affiliations:
University Hospital of Heidelberg,Heidelberg,Germany
,
Paul G. Richardson
Affiliations:
Dana-Farber Cancer Institute,Boston,United States
,
Mihaela Popa McKiver
Affiliations:
Bristol-Myers Squibb,Princeton,United States
,
Ying-Ming Jou
Affiliations:
Bristol-Myers Squibb,Princeton,United States
,
Suresh G. Shelat
Affiliations:
Bristol-Myers Squibb,Princeton,United States
,
Michael Robbins
Affiliations:
Bristol-Myers Squibb,Cambridge,United States
,
Brian Rafferty
Affiliations:
Bristol-Myers Squibb,Princeton,United States
Jesús San Miguel
Affiliations:
Clínica Universidad de Navarra, Centro de Investigación Médica Aplicada, IDISNA, CIBERONC,Pamplona,Spain
EHA Library. Richardson P. Jun 15, 2019; 266987; PS1370
Dr. Paul Richardson
Dr. Paul Richardson
Contributions
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Abstract

Abstract: PS1370

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

Background
Despite multiple therapeutic options for multiple myeloma (MM), duration of disease control decreases with each line of therapy and overall survival (OS) remains poor after treatment failure with proteasome inhibitors (PIs) and immunomodulatory drugs (Kumar SK et al. Leukemia 2017). Elotuzumab, an immunostimulatory monoclonal antibody targeting SLAMF7, enables selective killing of MM cells through multiple mechanisms of action and synergizes with the immunomodulatory drug pomalidomide (pom). The primary analysis (minimum follow-up [FU]: 9.1 months) of the open-label, randomized, ELOQUENT-3 study (NCT02654132) demonstrated a median progression-free survival (PFS) of 10.3 months for elotuzumab plus pom and dexamethasone (EPd) vs 4.7 mo for pom and dex (Pd) alone (HR 0.54, p=0.008). Preliminary analysis of OS suggested a trend in favor of EPd (Dimopoulos MA et al. N Engl J Med 2018). On the basis of these data, EPd was approved in the United States for the treatment of adult patients (pts) with MM and ≥2 prior therapies including lenalidomide (len) and a PI.

Aims
This non-prespecified analysis was conducted to provide a descriptive assessment of OS with EPd vs Pd in ELOQUENT-3 after extended FU. PFS and safety were also assessed. 

Methods
Eligible pts were adults with ≥2 prior lines of therapy (LoTs), including len and a PI (prior pom not permitted), who had MM that was refractory to last therapy and either refractory or relapsed and refractory to len and a PI. Pts were randomized 1:1 (stratified by prior LoTs [2–3 vs ≥4] and ISS stage at study entry [I–II vs III]) to receive EPd or Pd in 28-day cycles until disease progression or unacceptable toxicity. Elotuzumab: 10 mg/kg IV weekly in cycles 1–2 and 20 mg/kg IV every 4 weeks in cycles 3+. Pom: 4 mg orally on days 1–21 of each cycle. Dexamethasone: 40 mg (pts ≤75 years) or 20 mg (pts >75 years) weekly in each cycle. Primary endpoint was PFS per investigator assessment; secondary endpoints were overall response rate per investigator and OS. All pts provided written informed consent.

Results
In total, 60 pts were randomized to the EPd group and 57 to the Pd group. Clinically relevant baseline characteristics were balanced between treatment groups; median (range) age was 67 (36–81) years. Median (range) number of prior LoTs was 3 (2–8), and 68% (EPd) and 72% (Pd) of pts had MM that was refractory to both len and a PI. As of clinical data cut-off (29 Nov 2018, minimum FU 18.3 mo), there were a total of 90 PFS events (EPd: 40/60; Pd: 50/57). PFS rates (EPd vs Pd) were 43% vs 20% (12 mo) and 34% vs 11% (18 mo). In this updated assessment after 48 (EPd: 20/60; Pd: 28/57) of the 78 (62%) deaths required for the final analysis, OS curves continued to diverge, with a 46% reduction in the risk of death with EPd vs Pd (HR 0.54, 95% CI 0.30–0.96; Figure). Median (95% CI) OS was not reached (24.9–not estimable [NE]) with EPd and was 17.4 mo (13.8–NE) with Pd. OS rates (EPd vs Pd) were 79% vs 68% (12 mo) and 68% vs 49% (18 mo). Safety results were consistent with the primary analysis.

Conclusion
In this extended FU of ELOQUENT-3, EPd demonstrated sustained and clinically relevant PFS and OS benefits vs Pd, with no new safety signals. These data support the long-term favorable efficacy–safety profile of EPd and suggest this regimen could be considered as a standard of care for pts with relapsed/refractory MM after failure of len and a PI.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): Immunomodulatory thalidomide analog, Immunotherapy, Multiple myeloma, Refractory

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