TY - JOUR
T1 - CC-486 Maintenance after Stem Cell Transplantation in Patients with Acute Myeloid Leukemia or Myelodysplastic Syndromes
AU - de Lima, Marcos
AU - Oran, Betul
AU - Champlin, Richard E.
AU - Papadopoulos, Esperanza B.
AU - Giralt, Sergio A.
AU - Scott, Bart L.
AU - William, Basem M.
AU - Hetzer, Joel
AU - Laille, Eric
AU - Hubbell, Becky
AU - Skikne, Barry S.
AU - Craddock, Charles
N1 - Funding Information:
Financial disclosure: This study was funded by Celgene Corporation, Summit, NJ. The authors received editorial support during manuscript development from Sheila Truten and Kelly Dittmore of Medical Communication Company, Inc. (Wynnewood, PA) who were funded by Celgene Corporation. Analyses were performed by Celgene Corporation. The authors are fully responsible for all content and editorial decisions and had access to all study data.
Funding Information:
Financial disclosure: This study was funded by Celgene Corporation, Summit, NJ. The authors received editorial support during manuscript development from Sheila Truten and Kelly Dittmore of Medical Communication Company, Inc. (Wynnewood, PA) who were funded by Celgene Corporation. Analyses were performed by Celgene Corporation. The authors are fully responsible for all content and editorial decisions and had access to all study data., Conflict of interest statement: M.d.L.: Celgene Corporation, consultancy, research funding; Pfizer, board of directors or advisory committees; Incyte, consultancy; Amgen, consultancy; Spectrum, consultancy. B.O.: Celgene Corporation, AROG, and Astex, research funding. E.B.P.: spouse has leadership roles and stock ownership at Exelixis, Regulus, and Biogen. S.A.G.: Amgen, Celgene Corporation, Jazz Pharmaceuticals, Kite Pharma, Novartis, and Sanofi, consultancy; Spectrum, consultancy, research funding. B.L.S.: Celgene Corporation, honoraria, consultancy, research funding, speakers bureau; Novartis, research funding, speakers bureau; Alexion, honoraria, speakers bureau; Incyte, honoraria, speakers bureau; Acceleron, data and safety monitoring board; Agios Pharmaceuticals, honoraria, consultancy. B.M.W.: Miragen, consultancy, honoraria. J.H., E.L., B.H., and B.S.S.: Celgene Corporation, employment, equity ownership. C.C.: Celgene Corporation, honoraria, research funding; Jazz Pharmaceuticals, Pfizer, and Janssen, honoraria., Authorship statement: All authors contributed to, revised, and approved manuscript content and gave approval for submission to the journal.
Publisher Copyright:
© 2018
PY - 2018/10
Y1 - 2018/10
N2 - 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.)
AB - 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.)
KW - Acute myeloid leukemia
KW - Allogeneic stem cell transplantation
KW - CC-486
KW - Maintenance therapy
KW - Myelodysplastic syndromes
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UR - http://www.scopus.com/inward/citedby.url?scp=85050910620&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2018.06.016
DO - 10.1016/j.bbmt.2018.06.016
M3 - Article
C2 - 29933073
AN - SCOPUS:85050910620
SN - 1083-8791
VL - 24
SP - 2017
EP - 2024
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 10
ER -