CC-486 Maintenance after Stem Cell Transplantation in Patients with Acute Myeloid Leukemia or Myelodysplastic Syndromes.
CC-486 Maintenance after Stem Cell Transplantation in Patients with Acute Myeloid Leukemia or Myelodysplastic Syndromes.
复制标题
DOI：
10.1016/j.bbmt.2018.06.016
复制
发表时间：
2018-10
期刊：
影响因子：
--
通讯作者：
Craddock C
中科院分区：
文献类型：
--
作者：
de Lima M;Oran B;Champlin RE;Papadopoulos EB;Giralt SA;Scott BL;William BM;Hetzer J;Laille E;Hubbell B;Skikne BS;Craddock C
复发是急性髓系白血病（AML）和骨髓增生异常综合征（MDS）患者异基因干细胞移植（alloSCT）后治疗失败的主要原因。注射阿扎胞苷可以改善移植后的结果，但在暴露和依从性方面存在挑战。口服CC-486允许延长剂量以延长阿扎胞苷活性。我们研究了alloSCT后CC-486维持治疗的使用。纳入了在CC-486启动时（alloSCT后42 - 84天）形态学完全缓解的MDS或AML成人患者。患者接受4种CC-486给药方案中的1种，每28天为1周期，最多12个周期。终点包括安全性、药代动力学、移植物抗宿主病（GVHD）发生率、复发/进展率和生存率。在30例患者中，7例接受CC-486每日一次，每个周期持续7天（200 mg，n = 3; 300 mg，n = 4），23例接受CC-486每日一次，每个周期持续14天（150 mg，n = 4; 200 mg，n = 19 [扩展队列]）。3 - 4级不良事件不常见，各治疗方案的发生频率相似。标准合并用药未改变CC-486的药代动力学参数。3例患者（10%）发生了III级急性GVHD，9例发生了慢性GVHD。在28例可评价患者中，6例（21%）复发或疾病进展：7例接受7天给药的患者中有3例（43%），23例接受14天给药的患者中有3例（13%）。移植相关死亡率为3%。在19个月的随访中，未达到中位总生存期。7天和14天给药队列的估计1年生存率分别为86%和81%。CC-486维持治疗通常耐受良好，复发率、疾病进展率和GVHD率较低。CC-486维持可能允许表观遗传操纵同种异体移植后的同种异体反应性反应。研究结果需要在随机试验中确认。（ClinicalTrials.gov NCT 01835587。）
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.)
登录
查看更多内容
影响因子：
20.3
作者：
Goodyear, Oliver C.;Dennis, Mike;Craddock, Charles F.
通讯作者：
Craddock, Charles F.
影响因子：
20.3
作者：
Goodyear, Oliver;Agathanggelou, Angelo;Craddock, Charles
通讯作者：
Craddock, Charles
影响因子：
20.3
作者：
Greenberg, P;Cox, C;Bennett, J
通讯作者：
Bennett, J
DOI：
10.1016/j.bbmt.2014.11.007
发表时间：
2015-03
期刊：
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
影响因子：
--
作者：
Bejanyan N;Weisdorf DJ;Logan BR;Wang HL;Devine SM;de Lima M;Bunjes DW;Zhang MJ
通讯作者：
Zhang MJ
影响因子：
4.3
作者：
de Lima, Marcos;Porter, David L.;Battiwalla, Minoo;Bishop, Michael R.;Giralt, Sergio A.;Hardy, Nancy M.;Kroeger, Nicolaus;Wayne, Alan S.;Schmid, Christoph
通讯作者：
Schmid, Christoph