Blood Journal
Leading the way in experimental and clinical research in hematology

A high rate of durable responses with romidepsin, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma

  1. Simon J. Harrison13,
  2. Hang Quach25,
  3. Emma Link6,
  4. John F. Seymour1,2,
  5. David S. Ritchie13,
  6. Sam Ruell7,
  7. Joanne Dean6,
  8. Henry Januszewicz1,
  9. Ricky Johnstone2,8,
  10. Paul Neeson3,
  11. Michael Dickinson1,2,
  12. Jean Nichols9, and
  13. H. Miles Prince14
  1. 1Haematology Department, Peter MacCallum Cancer Centre, East Melbourne, Australia;
  2. 2University of Melbourne, Melbourne, Australia;
  3. 3Haematology Immunology Translational Research Laboratory, Research Division, Peter MacCallum Cancer Centre, East Melbourne, Australia;
  4. 4Faculty of Medicine, Monash University, Victoria, Australia;
  5. 5Haematology Service, Monash Medical Centre, Melbourne, Australia;
  6. 6Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, East Melbourne, Australia;
  7. 7Clinical Trials Unit, Peter MacCallum Cancer Centre, East Melbourne, Australia;
  8. 8Cancer Immunology Program, Research Division, Peter MacCallum Cancer Centre, East Melbourne, Australia; and
  9. 9Celgene Corporation, Summit, NJ

Abstract

We report results from a study exploring the combination of romidepsin, bortezomib, and dexamethasone for the treatment of patients with multiple myeloma (MM) previously treated with > 1 prior therapy. The primary objective was to determine the maximum tolerated dose (MTD) of the combination using a novel accelerated dose-escalation schedule in patients with relapsed or refractory MM. The secondary objective was to determine overall response (OR), time to progression (TTP), and overall survival (OS). The MTD identified was bortezomib 1.3 mg/m2 (days 1, 4, 8, and 11), dexamethasone 20 mg (days 1, 2, 4, 5, 8, 9, 11, and 12), and romidepsin 10 mg/m2 (days 1, 8, and 15) every 28 days. Thrombocytopenia (64%) was the most common ≥ grade 3 hematologic toxicity. Peripheral neuropathy occurred in 76% of patients (n = 19) (≥ grade 3, 8%; 95% confidence interval [CI] 1%-26%). Maintenance romidepsin 10 mg/m2 (on days 1 and 8 of a 28-day cycle) proved feasible, with 12 patients receiving a median of 7.5 cycles (range: 1-29). An OR (M-protein) of > minor response (MR) was seen in 18 of 25 patients (72%); 2 (8%) had complete remissions (CRs) and 13 (52%) had partial responses (PRs), including 7 (28%) with very good PRs (VGPRs). The median TTP was 7.2 (95% CI: 5.5-19.6) months, and the median OS was > 36 months. This regimen shows activity with manageable toxicity and warrants further evaluation. This trial was registered at www.clinicaltrials.gov as NCT00431990.

  • Submitted February 28, 2011.
  • Accepted August 30, 2011.
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