| Title |
The Clinical Pharmacology of Elotuzumab
|
|---|---|
| Published in |
Clinical Pharmacokinetics, August 2017
|
| DOI | 10.1007/s40262-017-0585-6 |
| Pubmed ID | |
| Authors |
Chaitali Passey, Jennifer Sheng, Johanna Mora, Amol Tendolkar, Michael Robbins, Robert Dodge, Amit Roy, Akintunde Bello, Manish Gupta |
| 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. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 33% |
| Unknown | 2 | 67% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 67% |
| Scientists | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 24 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 6 | 25% |
| Other | 2 | 8% |
| Student > Master | 2 | 8% |
| Student > Ph. D. Student | 2 | 8% |
| Student > Doctoral Student | 1 | 4% |
| Other | 3 | 13% |
| Unknown | 8 | 33% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 11 | 46% |
| Agricultural and Biological Sciences | 2 | 8% |
| Immunology and Microbiology | 2 | 8% |
| Business, Management and Accounting | 1 | 4% |
| Unknown | 8 | 33% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 August 2017.
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#17,910,703
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Outputs from Clinical Pharmacokinetics
#1,296
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Outputs of similar age from Clinical Pharmacokinetics
#21
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