BMSEHA15
Published online 4 February 2010
(Haematologica 2010, 10.3324/haematol.2009.008003)
Copyright © 2010 by Ferrata Storti Foundation
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Article

A phase 1 multidose study of dacetuzumab (SGN-40; humanized anti-CD40 mAb) in patients with multiple myeloma

Mohamad Hussein1, James R. Berenson2, Ruben Niesvizky3, Nikhil Munshi4, Jeffrey Matous5, Ronald Sobecks1, Kate Harrop6, Jonathan G. Drachman6, Nancy Whiting6

1 The Cleveland Clinic Foundation, Cleveland, OH, USA
2 Institute for Myeloma and Bone Cancer Research, West Hollywood, CA, USA
3 Weill Cornell Medical College, New York, NY, USA
4 Dana Farber Cancer Institute, Boston VA Healthcare System, Boston, MA, USA
5 Rocky Mountain Cancer Center, Denver, CO, USA
6 Seattle Genetics, Inc., Bothell, WA, USA

Correspondence: Current address: Mohamad Hussein, MD, Celgene, 86 Morris Avenue, Summit NJ, 07901, USA. Phone: international +908.6739000. Fax: international (908) 6739774. E-mail: mhussein{at}celgene.com

ABSTRACT

This first-in-human, phase 1 study evaluated the safety, maximum-tolerated dose (MTD), pharmacokinetics, and antitumor activity of dacetuzumab in 44 patients with advanced multiple myeloma. Patients received intravenous dacetuzumab, either in 4 uniform weekly doses (first 4 cohorts) or using a 5-week intrapatient dose escalation schedule (7 subsequent cohorts; the last 3 cohorts received steroid premedication). An initial dose of 4 mg/kg dacetuzumab exceeded the MTD for uniform weekly dosing. Intrapatient dose escalation with steroid premedication appeared effective in reducing symptoms of cytokine release syndrome (CRS) and the MTD with this dosing schema was 12 mg/kg/week. Adverse events potentially related to dacetuzumab included CRS symptoms, noninfectious ocular inflammation, and elevated hepatic enzymes. Peak dacetuzumab blood levels increased with dose. Nine patients (20%) had a best clinical response of stable disease. The observed safety profile suggested that dacetuzumab may be combined with other multiple myeloma therapies. Two combination trials are ongoing.

Key words: multiple myeloma, dacetuzumab, SGN-40, CD40, immunotherapy.