Pomalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 1 and 2 trial

Blood. 2016 Aug 25;128(8):1059-62. doi: 10.1182/blood-2016-04-710822. Epub 2016 Jul 5.

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.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amyloidosis / drug therapy*
  • Dexamethasone / adverse effects
  • Dexamethasone / therapeutic use*
  • Female
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Survival Analysis
  • Thalidomide / adverse effects
  • Thalidomide / analogs & derivatives*
  • Thalidomide / therapeutic use
  • Treatment Outcome

Substances

  • Thalidomide
  • Dexamethasone
  • pomalidomide

Associated data

  • ClinicalTrials.gov/NCT01570387