title: 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.
authors.affiliation: Haematology Department, Peter MacCallum Cancer Centre, East Melbourne, Australia. simon.harrison@petermac.org
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Harrison
authors.forename: Hang
authors.initials: H
authors.lastname: Quach
authors.forename: Emma
authors.initials: E
authors.lastname: Link
authors.forename: John F
authors.initials: JF
authors.lastname: Seymour
authors.forename: David S
authors.initials: DS
authors.lastname: Ritchie
authors.forename: Sam
authors.initials: S
authors.lastname: Ruell
authors.forename: Joanne
authors.initials: J
authors.lastname: Dean
authors.forename: Henry
authors.initials: H
authors.lastname: Januszewicz
authors.forename: Ricky
authors.initials: R
authors.lastname: Johnstone
authors.forename: Paul
authors.initials: P
authors.lastname: Neeson
authors.forename: Michael
authors.initials: M
authors.lastname: Dickinson
authors.forename: Jean
authors.initials: J
authors.lastname: Nichols
authors.forename: H Miles
authors.initials: HM
authors.lastname: Prince
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D015331:Cohort Studies; D047630:Depsipeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D055502:Secondary Prevention; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D001897:Boronic Acids; D047630:Depsipeptides; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone; C087123:romidepsin