Relapsed/refractory patients

EHA 2018 | Pomalidomide/dexamethasone with or without elotuzumab: the ELOQUENT-3 trial

The 23rd Congress of the European Hematology Association (EHA) took place in Stockholm from 14–17 June 2018. On Sunday 17 June, an oral session took place during which, Meletios A. Dimopoulos, Professor and Chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine, Athens, Greece, presented results of the ELOQUENT-3 phase II clinical trial.

ELOQUENT-3 examines the efficacy of pomalidomide (pom) and dexamethasone (dex) with or without administration of elotuzumab (elo). Elo is an immunostimulatory monoclonal antibody, which targets SLAMF7 (Signaling Lymphocyte Activation Molecule Family member 7), a cell- surface glycoprotein highly expressed in multiple myeloma (MM) cells but not in healthy cells. Elo with lenalidomide (len)/dex has shown sustained PFS benefits and acceptable safety in patients (pts) with relapsed/refractory MM (RRMM) in the phase III ELOQUENT-2 trial.

Pom has been indicated for RRMM pts who are refractory to len. Therefore, the rationale for the ELOQUENT-3 trial is that elo with pom may have synergistic effects similar to those observed with elo and len and may therefore provide an effective treatment for pts who are refractory to len. The primary endpoint of the study is to compare the progression-free survival (PFS) of elo/pom/dex vs pom/dex in pts with RRMM.

Data is given as elo/pom/dex vs pom/dex

Study Design
  • Pts with ≥ 2 prior lines of therapy, including len and a proteasome inhibitors (PI); pom not permitted
  • Pts refractory to last therapy and refractory or RR to len and a PI
  • 1:1 randomization
  • 28-days cycles until disease progression/unacceptable toxicity
  • Elo = 10 mg/kg intravenously (IV) weekly on cycles 1−2 (days, 1, 8, 15, 22); 20 mg/kg IV every 4 weeks (day, 1) thereafter
  • Pom = 4 mg orally on days 1-21 of each cycle
  • Dex = 40 mg or 20 mg for pts > 75 years (days: 1, 8, 15, and 22)
  • Secondary endpoints = overall response rate (ORR) and overall survival (OS)
Key Data
  • Pts = 60 vs 57
  • Median age = 67
  • Median (range) number of prior lines of treatment = 3 (2-8)
  • Refractory pts = len = 87%; PIs = 80%; len/PI = 70%
  • Minimum follow-up = 9.1 months (database lock = 21 February 2018)
  • Pts remaining on treatment = 40% (24/60) vs 20% (11/55)
  • Main reason for discontinuation = disease progression, 43% vs 56%
  • Elo/pom/dex = 46% reduction in risk of progression or death vs pom/dex (hazard ratio [HR] 0.54; 95% CI 0.34−0.86; P = 0.0078)
  • Median PFS = 10.3 (95% CI 5.6−not estimable) vs 4.7 months (95% CI 2.8−7.2)
  • ORR = 53% (95% CI 40−66) vs 26% (95% CI 16−40) (odds ratio 3.25; 95% CI 1.49 7.11; P = 0.0029)
  • Very good partial response (VGPR) or ≥ = 20% vs 9% of pts
  • OS, although not mature at this time, showed a positive trend favoring elo/pom/dex over pom/dex (HR 0.62; 95% CI: 0.30 to 1.28)
  • Adverse events (AEs) = neutropenia = 13% vs 27%, grade 3-4; anemia = 10% vs 20%
  • Infusion-related reactions (IRR) = 3 pts (5%); all grade 1-2
  • AEs leading to discontinuation = 18% vs 24% of pts
  • Deaths = 13 vs 18; mostly due to disease progression (13% vs 25% of treated pts)
Conclusions

The highly significant 46% reduction in risk of progression or death in pts treated with elo/pom/dex vs pom/dex reflects that this treatment is clinically meaningful and may provide a new treatment option to RRMM pts who are refractory to len and a PI.

References
  1. Dimopoulos M.A. et al. 23rd Congress of the European Hematology Association; 2018 June 14–17; Stockholm, SE. Abstract #LB2606.
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