The Clinical Pharmacology of Elotuzumab

  • Chaitali Passey
  • Jennifer Sheng
  • Johanna Mora
  • Amol Tendolkar
  • Michael Robbins
  • Robert Dodge
  • Amit Roy
  • Akintunde Bello
  • Manish Gupta
Review Article

Abstract

Novel treatment options are needed to improve long-term outcomes for patients with multiple myeloma (MM). In this article, we comprehensively review the clinical pharmacology of elotuzumab, a first-in-class monoclonal anti-SLAMF7 antibody approved in combination with lenalidomide and dexamethasone (ELd) for the treatment of patients with MM and one to three prior therapies. Elotuzumab has a dual mechanism of action to specifically kill myeloma cells: binding SLAMF7 on myeloma cells facilitates natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC), and direct engagement of SLAMF7 on NK cells further enhances NK cell activity. Elotuzumab administration causes transient elevations of selected cytokines (tumor necrosis factor-α, interferon-γ-induced protein-10 and monocyte chemoattractant protein-1). The temporary nature of these elevations (greatest after the first dose, with a trend to return to baseline by day 7) suggests a low likelihood of facilitating clinically meaningful drug–drug interactions. Elotuzumab exposure increases more than proportionally to dose and >80% SLAMF7 receptor occupancy is achieved with the approved elotuzumab 10 mg/kg regimen. Population pharmacokinetic data from 375 patients demonstrated weight-based dosing is appropriate for elotuzumab, and that ethnicity and hepatic/renal function have minimal effects on exposure. Exposure–response analysis of patients treated with ELd demonstrated that increased elotuzumab exposure does not elevate the risk of grade 3+ adverse events (AEs) or AEs leading to discontinuation/death. Elotuzumab antidrug antibodies occurred in 18.5% of patients treated with ELd or elotuzumab plus bortezomib and dexamethasone, but were generally transient and did not affect elotuzumab efficacy or safety. A monotherapy study indicated elotuzumab does not have clinically relevant effects on QT intervals.

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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Chaitali Passey
    • 1
  • Jennifer Sheng
    • 1
  • Johanna Mora
    • 1
  • Amol Tendolkar
    • 1
  • Michael Robbins
    • 1
  • Robert Dodge
    • 1
  • Amit Roy
    • 1
  • Akintunde Bello
    • 1
  • Manish Gupta
    • 1
  1. 1.Clinical Pharmacology and PharmacometricsBristol-Myers SquibbPrincetonUSA

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