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Phase 2 trial of the histone deacetylase inhibitor romidepsin for the treatment of refractory multiple myeloma†‡§

  1. Ruben Niesvizky MD1,¶,*,
  2. Scott Ely MD, MPH2,
  3. Tomer Mark MD1,
  4. Sangeeta Aggarwal MD3,
  5. Janice L Gabrilove MD4,
  6. John J. Wright MD, PhD5,
  7. Selina Chen-Kiang PhD6,
  8. Joseph A Sparano MD7

Article first published online: 22 SEP 2010

DOI: 10.1002/cncr.25584

Issue

Cancer

Cancer

Volume 117, Issue 2, pages 336–342, 15 January 2011

Additional Information

How to Cite

Niesvizky, R., Ely, S., Mark, T., Aggarwal, S., Gabrilove, J. L., Wright, J. J., Chen-Kiang, S. and Sparano, J. A. (2011), Phase 2 trial of the histone deacetylase inhibitor romidepsin for the treatment of refractory multiple myeloma. Cancer, 117: 336–342. doi: 10.1002/cncr.25584

Author Information

  1. 1

    Department of Medicine, Division of Hematology Oncology, Center of Excellence of Lymphoma and Myeloma, Weill Cornell Medical College/New York Presbyterian Hospital, New York, New York

  2. 2

    Department of Pathology and Laboratory Medicine, Weill Cornell Medical College/New York Presbyterian Hospital, New York, New York

  3. 3

    Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York

  4. 4

    Tisch Cancer Institute, Mt. Sinai School of Medicine, New York, New York

  5. 5

    Investigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

  6. 6

    Department of Pathology and Laboratory Medicine and Microbiology and Immunology, Weill Cornell Medical College, New York, New York

  7. 7

    Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York

  1. Fax: (212) 746-5536

*520 East 70th Street, Starr 341, New York, NY 10021

  1. †

    This article is a U.S. Government work and, as such, is in the public domain in the United States of America.

  2. ‡

    Presented in part at the 2005 American Society of Hematology Meeting; December 5-8, 2005; New Orleans, Louisiana.

  3. §

    The authors thank Mr. David Jayabalan for his help in the production of the artwork.

Publication History

  1. Issue published online: 5 JAN 2011
  2. Article first published online: 22 SEP 2010
  3. Manuscript Accepted: 29 JUN 2010
  4. Manuscript Revised: 18 MAY 2010
  5. Manuscript Received: 24 MAR 2010

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Keywords:

  • romidepsin;
  • myeloma;
  • recurrent/refractory;
  • histone deacetylase;
  • inhibitor;
  • phase 2

Abstract

BACKGROUND:

Epigenetic dysregulation is a hallmark of cancer, including multiple myeloma. Inhibitors of histone deacetylases (HDACs) induce DNA hyperacetylation by inhibiting removal of acetyl groups from amino tails on histone proteins, thereby uncoiling condensed chromatin favoring transcription of silenced genes, including tumor suppressor genes. Romidepsin is an HDAC inhibitor that exhibits antiproliferative and apoptotic effects against multiple myeloma cell lines.

METHODS:

A phase 2 trial was performed of romidepsin in patients with multiple myeloma who were refractory to standard therapy. Treatment was comprised of romidepsin (13 mg/m2) given as a 4-hour intravenous infusion on Days 1, 8, and 15 every 28 days). Thirteen patients received a median of 2 cycles of therapy (range, 1-7 cycles).

RESULTS:

Although no patients had an objective response, 4 of 12 patients with secretory myeloma exhibited evidence of M-protein stabilization, and several other patients experienced improvement in bone pain and resolution of hypercalcemia.

CONCLUSIONS:

The results of the current study demonstrate that romidepsin, as a single agent, is unlikely to be associated with a response rate of ≥30% in patients with refractory myeloma, although there was some clinical evidence suggesting a biological effect associated with therapy. Cancer 2011. Published 2010 by the American Cancer Society.

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