Journal
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
Volume 24, Issue 10, Pages 2017-2024Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2018.06.016
Keywords
CC-486; Acute myeloid leukemia; Myelodysplastic syndromes; Allogeneic stem cell transplantation; Maintenance therapy
Categories
Funding
- Celgene Corporation, Summit, NJ
- Celgene Corporation
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Relapse is the main cause of treatment failure after allogeneic stem cell transplant (alloSCT) in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Injectable azacitidine can improve post-transplant outcomes but presents challenges with exposure and compliance. Oral CC-486 allows extended dosing to prolong azacitidine activity. We investigated use of CC-486 maintenance therapy after alloSCT. Adults with MDS or AML in morphologic complete remission at CC-486 initiation (42 to 84 days 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 per cycle (200 mg, n = 3; 300 mg, n = 4) and 23 for 14 days per 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 Ill acute GVHD and 9 experienced chronic GVHD. Of 28 evaluable patients, 6 (21%) relapsed or had progressive disease: 3 of 7 patients (43%) who had received 7-day dosing and 3 of 23 (13%) who had 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 rates were 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. (C) 2018 American Society for Blood and Marrow Transplantation.
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