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Cited by 342Multiple Myeloma Research and TreatmentsMonoclonal and Polyclonal Antibodies ResearchChronic Lymphocytic Leukemia Research

The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.

A phase 1, multicenter, open-label, dose escalation study of elotuzumab in patients with advanced multiple myeloma

Open access
Zonder, Jeffrey A., Mohrbacher, Ann F., Singhal, Seema, van Rhee, Frits, Bensinger, William I., Ding, Han, Fry, John, Afar, Daniel E. H., Singhal, Anil K.·2012·Blood
DOI 10.1182/blood-2011-06-360552PMC PMC4467882
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Abstract

This multicenter, first-in-human study evaluated the safety, tolerability, and pharmacokinetic and pharmacodynamic properties of the anti-CS1 monoclonal antibody elotuzumab. A standard 3 + 3 design was used to determine maximum tolerated dose; dose-limiting toxicities were assessed during cycle 1. Thirty-five patients with relapsed/refractory multiple myeloma were treated with intravenous elotuzumab at doses ranging from 0.5 to 20 mg/kg every 2 weeks. Patients who achieved at least stable disease after 4 treatments could receive another 4 treatments. No maximum tolerated dose was identified up to the maximum planned dose of 20 mg/kg. The most common adverse events, regardless of attribution, were cough, headache, back pain, fever, and chills. Adverse events were generally mild to moderate in severity, and adverse events attributed to study medication were primarily infusion-related. Plasma elotuzumab levels and terminal half-life increased with dose whereas clearance decreased, suggesting target-mediated clearance. CS1 on bone marrow–derived plasma cells was reliably saturated (≥ 95%) at the 10-mg/kg and 20-mg/kg dose levels. Using the European Group for Bone and Marrow Transplantation myeloma response criteria, 9 patients (26.5%) had stable disease. In summary, elotuzumab was generally well tolerated in this population, justifying further exploration of this agent in combination regimens.

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Metadata

Authors
Zonder, J. A., Mohrbacher, A. F., Singhal, S., van Rhee, F., Bensinger, W. I., Ding, H., Fry, J., Afar, D. E. H., & Singhal, A. K.
Affiliations
  • Wayne State University (US)
  • University of Southern California (US)
  • Northwestern University (US)
  • Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR;
  • Fred Hutch Cancer Center (US)
  • AbbVie Biotherapeutics (United States) (US)
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
2012-07-19
Volume
120
Issue
3
Pages
552-559
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood-2011-06-360552
PMC
PMC4467882
OpenAlex
W2000130439
Cited by
342
References
42
Citations by year
2026: 3 · 2025: 2 · 2024: 8 · 2023: 10 · 2022: 16 · 2021: 22 · 2020: 34 · 2019: 25 · 2018: 42 · 2017: 41 · 2016: 48 · 2015: 38 · 2014: 28 · 2013: 21 · 2012: 4
FWCI
11.63
Type
journal article
Language
en
Open access
Locations
  • Blood (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Bristol-Myers Squibb
  • National Cancer Institute (P01CA055819)
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
  • Health Sciences › Medicine › Hematology › Chronic Lymphocytic Leukemia Research
Keywords
elotuzumab, multiple myeloma, CS1, syndecan-1, monoclonal antibodies, dose escalation, maximum tolerated dose, dose-limiting toxicity, pharmacokinetics, pharmacodynamics, safety and tolerability, relapsed/refractory multiple myeloma, stable disease
MeSH terms
Aged, Aged, 80 and over, Antineoplastic Agents, Bone Marrow, Dose-Response Relationship, Drug, Female, Humans, Male, Middle Aged, Multiple Myeloma, Severity of Illness Index, Treatment Outcome, Lymphocyte Count, Chemokine CXCL10, Antibodies, Neutralizing, Antibodies, Monoclonal, Humanized

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