Phase II trial of temsirolimus in patients with relapsed or refractory multiple myeloma

Farag, Sherif S.; Zhang, Shuhong; Jansak, Buffy S.; Wang, Xiaojing; Kraut, Eric; Chan, Kenneth; Dancey, Janet E.; Grever, Michael R.

doi:10.1016/j.leukres.2009.01.039

« Previous Next »Leukemia Research
Volume 33, Issue 11 , Pages 1475-1480, November 2009

Phase II trial of temsirolimus in patients with relapsed or refractory multiple myeloma

Sherif S. Farag
- Departments of Internal Medicine and Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States
- Corresponding author at: Division of Hematology and Oncology, Department of Internal Medicine, Indiana University School of Medicine, 635 Barnhill Drive, Room 224G, Indianapolis, IN 46202, United States. Tel.: +1 317 278 0460; fax: +1 317 278 2262.
Shuhong Zhang
- Departments of Internal Medicine and Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States
Buffy S. Jansak
- Division of Hematology and Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH, United States
Xiaojing Wang
- Departments of Internal Medicine and Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States
Eric Kraut
- Division of Hematology and Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH, United States
Kenneth Chan
- College of Pharmacy, The Ohio State University, Columbus, OH, United States
Janet E. Dancey
- National Cancer Institute, Bethesda, MD, United States
Michael R. Grever
- Division of Hematology and Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH, United States

Received 17 November 2008; received in revised form 28 January 2009; accepted 30 January 2009. published online 07 March 2011.

Abstract

In a phase II trial, 16 patients with relapsed refractory multiple myeloma received temsirolimus 25mg I.V. weekly until progression. One partial response and 5 minor responses were observed for a total response rate of 38%. The median time to progression was 138 days. Grade 3–4 toxicity included fatigue (n=3), neutropenia (n=2), thrombocytopenia (n=2), interstitial pneumonitis (n=1), stomatitis (n=1) and diarrhea (n=1). Clinical activity was associated with a higher area under the curve (AUC) and maximal reduction in phosphorylated p70^S6K and 4EBP1 in peripheral blood mononuclear cells. At the dose and schedule used, temsirolimus had low single agent activity. Investigation of alternate dosing schedules and use in combinations is indicated.