Phase I study of pomalidomide MTD, safety and efficacy in patients with refractory multiple myeloma who have received lenalidomide and bortezomib
Mené sur 38 patients atteints d'un myélome multiple récidivant et réfractaire au lénalidomide et au bortezomib, cet essai de phase I évalue la dose maximale tolérée du pomalidomide par voie orale, avec ou sans dexaméthasone
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 4 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/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 4 dose-limiting toxicities (grade 4 neutropenia) at 5 mg/day so the MTD was 4 mg/day. Peripheral neuropathy and venous thromboembolism rates were low (≤ 5%). Among the 38 patients enrolled (including 22 with added dexamethasone), 42% achieved minimal response or better, 21% partial response or better, and 3% 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/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. Study registered at http://www.clinicaltrials.gov as NCT00833833.