CC-486 maintenance after stem cell transplantation in patients with acute myeloid leukemia or myelodysplastic syndromes Journal Article


Authors: de Lima, M.; Oran, B.; Champlin, R. E.; Papadopoulos, E. B.; Giralt, S. A.; Scott, B. L.; William, B. M.; Hetzer, J.; Laille, E.; Hubbell, B.; Skikne, B. S.; Craddock, C.
Article Title: CC-486 maintenance after stem cell transplantation in patients with acute myeloid leukemia or myelodysplastic syndromes
Abstract: 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 III 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. (ClinicalTrials.gov NCT01835587.) © 2018
Keywords: adult; cancer survival; controlled study; survival rate; major clinical study; overall survival; busulfan; allogeneic stem cell transplantation; neutropenia; area under the curve; diarrhea; unspecified side effect; cancer patient; controlled clinical trial; multiple cycle treatment; anemia; nausea; thrombocytopenia; vomiting; dehydration; maintenance therapy; cyclophosphamide; cancer mortality; thiotepa; abdominal pain; lymphocytopenia; pneumonia; survival time; cancer regression; acute graft versus host disease; chronic graft versus host disease; myelodysplastic syndrome; multicenter study; graft versus host reaction; drug clearance; time to maximum plasma concentration; drug blood level; drug half life; azacitidine; myelodysplastic syndromes; device infection; acute myeloid leukemia; maintenance chemotherapy; human; male; female; article; maximum concentration; cc-486
Journal Title: Biology of Blood and Marrow Transplantation
Volume: 24
Issue: 10
ISSN: 1083-8791
Publisher: Elsevier Inc.  
Date Published: 2018-10-01
Start Page: 2017
End Page: 2024
Language: English
DOI: 10.1016/j.bbmt.2018.06.016
PUBMED: 29933073
PROVIDER: scopus
PMCID: PMC8059405
DOI/URL:
Notes: Article -- Export Date: 3 December 2018 -- Source: Scopus
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  1. Sergio Andres Giralt
    965 Giralt