Yazarlar : Zonder JA, Mohrbacher AF, Singhal S, van Rhee F, Bensinger WI, Ding H, Fry J, Afar DE, Singhal AK.

Yayın : Blood.

Yayın Yılı : 2011

Pubmed Linki : http://www.ncbi.nlm.nih.gov/pubmed/22184404

Konu : Myelom

Literatür İçeriği :  

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 utilized to determine maximum tolerated dose (MTD); 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 0.5-20 mg/kg every 2 weeks. Patients who achieved at least stable disease (SD) after 4 treatments could receive another 4 treatments. No MTD was identified up to the maximum planned dose of 20 mg/kg. The most common adverse events (AEs), regardless of attribution, were cough, headache, back pain, fever, and chills. AEs were generally mild to moderate in severity, and AEs attributed to study medication were primarily infusion-related. Plasma elotuzumab levels and terminal half-life increased with dose while 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 SD. In summary, elotuzumab was generally well-tolerated in this population, justifying further exploration of this agent in combination regimens.

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