PDF(Pubmed)
Abstract：
UNASSIGNED: Discontinuation of tyrosine kinase inhibitor (TKI) treatment is emerging as the main therapy goal for Chronic Myeloid Leukemia (CML) patients. The DESTINY trial showed that TKI dose reduction prior to cessation can lead to an increased number of patients achieving sustained treatment free remission (TFR). However, there has been no systematic investigation to evaluate how dose reduction regimens can further improve the success of TKI stop trials.
UNASSIGNED: Here, we apply an established mathematical model of CML therapy to investigate different TKI dose reduction schemes prior to therapy cessation and evaluate them with respect to the total amount of drug used and the expected TFR success.
UNASSIGNED: Our systematic analysis confirms clinical findings that the overall time of TKI treatment is a major determinant of TFR success, while highlighting that lower dose TKI treatment for the same duration is equally sufficient for many patients. Our results further suggest that a stepwise dose reduction prior to TKI cessation can increase the success rate of TFR, while substantially reducing the amount of administered TKI.
UNASSIGNED: Our findings illustrate the potential of dose reduction schemes prior to treatment cessation and suggest corresponding and clinically testable strategies that are applicable to many CML patients.
UNASSIGNED: Here, we apply an established mathematical model of CML therapy to investigate different TKI dose reduction schemes prior to therapy cessation and evaluate them with respect to the total amount of drug used and the expected TFR success.
UNASSIGNED: Our systematic analysis confirms clinical findings that the overall time of TKI treatment is a major determinant of TFR success, while highlighting that lower dose TKI treatment for the same duration is equally sufficient for many patients. Our results further suggest that a stepwise dose reduction prior to TKI cessation can increase the success rate of TFR, while substantially reducing the amount of administered TKI.
UNASSIGNED: Our findings illustrate the potential of dose reduction schemes prior to treatment cessation and suggest corresponding and clinically testable strategies that are applicable to many CML patients.
摘要：
未经批准：停止酪氨酸激酶抑制剂（TKI）治疗正在成为慢性髓系白血病（CML）患者的主要治疗目标。DESTINY试验表明，停药前减少TKI剂量可导致获得持续治疗缓解（TFR）的患者数量增加。然而,目前还没有系统的研究来评估减量方案如何进一步提高TKI终止试验的成功率.
未经评估：这里，我们应用已建立的CML治疗数学模型,在治疗停止前研究不同的TKI减量方案,并根据药物使用总量和预期的TFR成功率进行评估.
UNASSIGNED：我们的系统分析证实了临床发现，TKI治疗的总体时间是TFR成功的主要决定因素，同时强调相同持续时间的较低剂量TKI治疗对许多患者同样足够。我们的结果进一步表明，在停止TKI之前逐步减少剂量可以增加TFR的成功率，同时大幅减少TKI的给药量。
UNASSIGNED：我们的研究结果说明了在停止治疗之前减少剂量方案的潜力，并提出了适用于许多CML患者的相应和临床可测试的策略。
未经评估：这里，我们应用已建立的CML治疗数学模型,在治疗停止前研究不同的TKI减量方案,并根据药物使用总量和预期的TFR成功率进行评估.
UNASSIGNED：我们的系统分析证实了临床发现，TKI治疗的总体时间是TFR成功的主要决定因素，同时强调相同持续时间的较低剂量TKI治疗对许多患者同样足够。我们的结果进一步表明，在停止TKI之前逐步减少剂量可以增加TFR的成功率，同时大幅减少TKI的给药量。
UNASSIGNED：我们的研究结果说明了在停止治疗之前减少剂量方案的潜力，并提出了适用于许多CML患者的相应和临床可测试的策略。
