Adults with MDS or AML in morphologic complete remission at CC-486 initiation (42 to 84days after alloSCT) were included. Patients received 1 of 4 CC-486 dosing schedules per 28-day cycle for up to 12 cycles. Endpoints included safety, pharmacokinetics, graft-versus-host disease (GVHD) incidence, relapse/progression rate, and survival. Of 30 patients, 7 received CC-486 once daily for 7 days a cycle (200 mg, n = 3; 300 mg, n = 4) and 23 for 14 days a cycle (150 mg, n = 4; 200 mg, n = 19 [expansion cohort]). Grades 3 to 4 adverse events were infrequent and occurred with similar frequency across regimens. Standard concomitant medications did not alter CC-486 pharmacokinetic parameters. Three patients (10%) experienced grade III acute GVHD and 9 experienced chronic GVHD. Of 28 assessable patients, 6 (21%) relapsed or had progressive disease: 3 of 7 patients (43%) received 7-day dosing and 3 of 23 (13%) received 14-day dosing. Transplant-related mortality was 3%. At 19 months of follow-up, median overall survival was not reached. Estimated 1-year survival was 86% and 81% in the 7-day and 14-day dosing cohorts, respectively.
CC-486 maintenance was generally well tolerated, with low rates of relapse, disease progression, and GVHD. CC-486 maintenance may permit epigenetic manipulation of the alloreactive response postallograft. Findings require confirmation in randomized trials. (ClinicalTrials.gov NCT01835587.)
- Maintenance therapy
- Allogeneic stem cell transplantation
- Myelodysplastic syndromes
- Acute myeloid leukemia