贝卢莫苏迪尔对慢性移植对宿主疾病患者的免疫抑制药理学产生影响
Rebecca Gonzalez1, Eric Gaskill1, Maya Padilla2
1Blood and Marrow Transplantation and Cellular Immunotherapy, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida; Department of Pharmacy, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.
Transplantation and cellular therapy
|June 24, 2023
概括
贝卢莫苏迪尔 (BEL) 在患有慢性移植对宿主疾病 (cGVHD) 的患者中显著增加西罗利斯和塔克罗利斯水平. 在将 BEL 与这些免疫抑制剂结合使用时,密切监测和剂量调整至关重要,以防止毒性.
科学领域:
- 药理学和治疗学 药理学和治疗学
- 瘤学和血液学 在线
- 免疫学 免疫学 免疫学
背景情况:
- 贝卢莫苏迪尔 (BEL) 是一种新型的ROCK2抑制剂,用于在多种疗法失败后治疗慢性移植对宿主疾病 (cGVHD).
- 实验室数据表明,BEL和狭窄治疗指数免疫抑制剂 (IS) 如塔克罗利斯和西罗利斯之间的潜在药理动力相互作用.
- 需要对BEL对并发IS药物水平的影响进行临床评估,以优化cGVHD管理的安全性和有效性.
研究的目的:
- 调查Belumosudil (BEL) 对cGVHD患者血中西罗和塔克罗的水平的影响.
- 评估开始BEL治疗后西罗和塔克罗的度-剂量 (C/D) 比率的变化.
- 为了确定超治疗性IS水平的发生率和指导剂量调整,当BEL被添加到现有的IS疗法时.
主要方法:
- 回顾性单中心研究分析了2019年2月至2023年2月的数据.
- 包括接受BEL与塔克罗利斯和/或西罗利斯同时治疗的患者,基线和随后的IS水平测量.
- 主要终点:C/D比率的变化;次要终点:超出范围的IS水平的发生率和剂量变化.
主要成果:
- 在BEL启动后,西罗利 (160%) 和塔克罗利 (113%) 接受者均观察到C/D比率的统计显著增加.
- 超治疗水平是常见的:57%的西罗利斯和19%的塔克罗利斯,尽管调整了剂量,但仍然存在.
- 停止使用BEL (100%) 导致C/D比率恢复到基线,证实了BEL对IS药物水平的影响.
结论:
- 贝卢莫苏迪尔 (BEL) 显著影响西罗和塔克罗的水平,需要仔细调整剂量和密切监测.
- 在开始BEL时,建议将塔克罗利斯剂量减少25%,西罗利斯剂量减少25-50%.
- 需要进一步的研究来充分描述BEL的药物相互作用,特别是与cGVHD患者的CYP3A抑制剂的相互作用.
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