title: Phase 1 study of pomalidomide MTD, safety, and efficacy in patients with refractory multiple myeloma who have received lenalidomide and bortezomib.
abstract: This phase 1 dose-escalation study determined the maximum tolerated dose (MTD) of oral pomalidomide (4 dose levels) administered on days 1 to 21 of each 28-day cycle in patients with relapsed and refractory multiple myeloma (RRMM). After four cycles, patients who progressed or had not achieved minimal response (serum and urine M-protein reduction of ≥ 25% and ≥ 50%) could receive dexamethasone 40 mg per week. Safety and efficacy were evaluated. Thirty-eight patients who had received both bortezomib and lenalidomide (median 6 prior therapies) were enrolled; 63% were refractory to both lenalidomide and bortezomib. There were four dose-limiting toxicities (grade 4 neutropenia) at 5 mg per day and so the MTD was 4 mg per day. Rates of peripheral neuropathy and venous thromboembolism were low (≤ 5%). Among the 38 patients enrolled (including 22 with added dexamethasone), 42% achieved minimal response or better, 21% achieved partial response or better, and 3% achieved complete response. Median duration of response, progression-free survival, and overall survival were 4.6, 4.6, and 18.3 months, respectively. Pomalidomide 4 mg per day on days 1 to 21 of each 28-day cycle, with or without dexamethasone (40 mg/week), has encouraging activity with manageable toxicity in RRMM, including those refractory to both lenalidomide and bortezomib. This study is registered at http://www.clinicaltrials.gov as #NCT00833833.
authors.affiliation: Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Paul_Richardson@dfci.harvard.edu
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.forename: David
authors.initials: D
authors.lastname: Siegel
authors.forename: Rachid
authors.initials: R
authors.lastname: Baz
authors.forename: Susan L
authors.initials: SL
authors.lastname: Kelley
authors.forename: Nikhil C
authors.initials: NC
authors.lastname: Munshi
authors.forename: Jacob
authors.initials: J
authors.lastname: Laubach
authors.forename: Daniel
authors.initials: D
authors.lastname: Sullivan
authors.forename: Melissa
authors.initials: M
authors.lastname: Alsina
authors.forename: Robert
authors.initials: R
authors.lastname: Schlossman
authors.forename: Irene M
authors.initials: IM
authors.lastname: Ghobrial
authors.forename: Deborah
authors.initials: D
authors.lastname: Doss
authors.forename: Nora
authors.initials: N
authors.lastname: Loughney
authors.forename: Laura
authors.initials: L
authors.lastname: McBride
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bilotti
authors.forename: Palka
authors.initials: P
authors.lastname: Anand
authors.forename: Lisa
authors.initials: L
authors.lastname: Nardelli
authors.forename: Sandra
authors.initials: S
authors.lastname: Wear
authors.forename: Gail
authors.initials: G
authors.lastname: Larkins
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Mohamad H
authors.initials: MH
authors.lastname: Zaki
authors.forename: Christian
authors.initials: C
authors.lastname: Jacques
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D001897:Boronic Acids / Q000008:administration & dosage*; D000069286:Bortezomib; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D011719:Pyrazines / Q000008:administration & dosage*; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; C467566:pomalidomide; D000077269:Lenalidomide