title: Pomalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 1 and 2 trial.
abstract: The objectives of a phase 1/2 trial of pomalidomide with dexamethasone for the treatment of light chain (AL) amyloidosis were to determine the safety, tolerability, maximum tolerated dose (MTD), recommended phase 2 dose, and hematologic and clinical response. A 3+3 dose-escalation phase (15 patients) was followed by an expansion cohort (12 patients) enrolled at the MTD. Pomalidomide was administered at 2 and 3 mg on days 1 to 28 (cohorts 1 and 2) and 4 mg on days 1 to 21 (cohort 3) every 28 days, with weekly dexamethasone at a dose of 20 mg. Twenty-seven patients with previously treated AL were enrolled, 15 during dose escalation (6 at 2 mg, 3 at 3 mg, and 6 at 4 mg) and 12 during dose expansion (all at 4 mg). One patient experienced dose-limiting toxicity at 4 mg; the MTD was determined as 4 mg. The most common grade ≥3 drug-related adverse events included myelosuppression and fatigue. Overall, hematologic response (HR) was 50% in 24 evaluable patients. The median time to best HR was 3 cycles, and median duration of HR was 15 months. Median overall survival has not yet been reached, with a median follow-up of 17.1 months and median event-free survival of 17.8 months. This trial was registered at www.clinicaltrials.gov as #NCT01570387.
authors.affiliation: Section of Hematology and Oncology, Department of Medicine, and Amyloidosis Center, Boston University School of Medicine and Boston Medical Center, Boston, MA.
authors.forename: Vaishali
authors.identifier: 0000-0002-6307-2445
authors.initials: V
authors.lastname: Sanchorawala
authors.affiliation: Section of Hematology and Oncology, Department of Medicine, and Amyloidosis Center, Boston University School of Medicine and Boston Medical Center, Boston, MA.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Shelton
authors.affiliation: Section of Hematology and Oncology, Department of Medicine, and Amyloidosis Center, Boston University School of Medicine and Boston Medical Center, Boston, MA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Lo
authors.affiliation: Section of Hematology and Oncology, Department of Medicine, and Amyloidosis Center, Boston University School of Medicine and Boston Medical Center, Boston, MA.
authors.forename: Cindy
authors.initials: C
authors.lastname: Varga
authors.affiliation: Section of Hematology and Oncology, Department of Medicine, and Amyloidosis Center, Boston University School of Medicine and Boston Medical Center, Boston, MA.
authors.forename: J Mark
authors.identifier: 0000-0001-7069-4528
authors.initials: JM
authors.lastname: Sloan
authors.affiliation: Section of Hematology and Oncology, Department of Medicine, and Amyloidosis Center, Boston University School of Medicine and Boston Medical Center, Boston, MA.
authors.forename: David C
authors.initials: DC
authors.lastname: Seldin
mesh_terms: D000328:Adult; D000368:Aged; D000686:Amyloidosis / Q000188:drug therapy*; D003907:Dexamethasone / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016019:Survival Analysis; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D013792:Thalidomide; D003907:Dexamethasone; C467566:pomalidomide