| Title |
An Integrated Assessment of the Effects of Immunogenicity on the Pharmacokinetics, Safety, and Efficacy of Elotuzumab
|
|---|---|
| Published in |
The AAPS Journal, January 2017
|
| DOI | 10.1208/s12248-016-0033-9 |
| Pubmed ID | |
| Authors |
Chaitali Passey, Johanna Mora, Robert Dodge, Leonid Gibiansky, Jennifer Sheng, Amit Roy, Akintunde Bello, Manish Gupta |
| Abstract |
Elotuzumab is a humanized, immunostimulatory anti-signaling lymphocytic activation molecule F7 (SLAMF7) IgG1 monoclonal antibody indicated in combination with lenalidomide and dexamethasone for patients with multiple myeloma (MM) who have received 1-3 prior therapies. We assessed the immunogenicity of elotuzumab as a monotherapy and in combination with bortezomib/dexamethasone and lenalidomide/dexamethasone in patients with MM in five clinical studies, including the pivotal ELOQUENT-2 trial (NCT01239797). Anti-drug antibody (ADA) prevalence was determined using a validated bridging assay. The prevalence of neutralizing antibodies (NAbs) was assessed in ADA-positive samples from ELOQUENT-2. Data from four trials of elotuzumab combined with lenalidomide/dexamethasone or bortezomib/dexamethasone (n = 390 evaluable patients) demonstrated that nine (2.3%) patients were ADA positive in baseline assays, 72 (18.5%) were ADA positive on-treatment or during follow-up, and two (0.5%) developed persistent ADAs. Patients treated with elotuzumab monotherapy had a higher incidence of elotuzumab ADAs than those on the combination therapy. In general, ADAs developed early and resolved after 2-4 months. Of 45 on-treatment ADA-positive patients in ELOQUENT-2, 19 had NAbs. Population pharmacokinetic modeling demonstrated an apparent increase in target-mediated elimination (higher V max, lower K M) in ADA-positive versus ADA-negative patients. ADAs were associated with lower elotuzumab steady-state exposure; however, this result may have been confounded by differential myeloma protein levels. ADAs/NAbs were not associated with hypersensitivity, infusion reactions, or loss of elotuzumab efficacy. Using a novel visualization, we also demonstrate that there is no clear relationship between the occurrence and titer values of ADA/NAbs and progression-free survival and best overall response status in patients treated with elotuzumab. |
X Demographics
The data shown below were collected from the profiles of 2 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 | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 50% |
| Scientists | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 28 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 28 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 5 | 18% |
| Student > Bachelor | 4 | 14% |
| Librarian | 2 | 7% |
| Other | 2 | 7% |
| Student > Doctoral Student | 2 | 7% |
| Other | 5 | 18% |
| Unknown | 8 | 29% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 7 | 25% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 14% |
| Biochemistry, Genetics and Molecular Biology | 3 | 11% |
| Agricultural and Biological Sciences | 3 | 11% |
| Business, Management and Accounting | 1 | 4% |
| Other | 1 | 4% |
| Unknown | 9 | 32% |
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 13 May 2017.
All research outputs
#15,442,314
of 22,952,268 outputs
Outputs from The AAPS Journal
#921
of 1,292 outputs
Outputs of similar age
#257,342
of 421,593 outputs
Outputs of similar age from The AAPS Journal
#23
of 32 outputs
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