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

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/m(2) (days 1, 4, 8, and 11), dexamethasone 20 mg (days 1, 2, 4, 5, 8, 9, 11, and 12), and romidepsin 10 mg/m(2) (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/m(2) (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.
AuthorsSimon J Harrison, Hang Quach, Emma Link, John F Seymour, David S Ritchie, Sam Ruell, Joanne Dean, Henry Januszewicz, Ricky Johnstone, Paul Neeson, Michael Dickinson, Jean Nichols, H Miles Prince
JournalBlood (Blood) Vol. 118 Issue 24 Pg. 6274-83 (Dec 08 2011) ISSN: 1528-0020 [Electronic] United States
PMID21911830 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Boronic Acids
  • Depsipeptides
  • Pyrazines
  • Bortezomib
  • Dexamethasone
  • romidepsin
Topics
  • Adult
  • Aged
  • Anti-Inflammatory Agents (administration & dosage, adverse effects, therapeutic use)
  • Antineoplastic Agents (administration & dosage, adverse effects, therapeutic use)
  • Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
  • Boronic Acids (administration & dosage, adverse effects, therapeutic use)
  • Bortezomib
  • Cohort Studies
  • Depsipeptides (administration & dosage, adverse effects, therapeutic use)
  • Dexamethasone (administration & dosage, adverse effects, therapeutic use)
  • Drug Administration Schedule
  • Drug Resistance, Neoplasm
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Multiple Myeloma (drug therapy, pathology, prevention & control)
  • Peripheral Nervous System Diseases (chemically induced, prevention & control)
  • Pyrazines (administration & dosage, adverse effects, therapeutic use)
  • Secondary Prevention
  • Survival Analysis
  • Thrombocytopenia (chemically induced, prevention & control)

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