Andy H Szeto, Tyler Bucci, Allison Deal, Anqi Zhu, Majd Ahmad, Amanda S Cass, Margaret R Sketch, Ryan Kemper, Joshua F Zeidner, Matthew C Foster, Benyam Muluneh, Daniel J Crona
{"title":"慢性髓系白血病患者对酪氨酸激酶抑制剂的反应。","authors":"Andy H Szeto, Tyler Bucci, Allison Deal, Anqi Zhu, Majd Ahmad, Amanda S Cass, Margaret R Sketch, Ryan Kemper, Joshua F Zeidner, Matthew C Foster, Benyam Muluneh, Daniel J Crona","doi":"10.1177/10600280211044160","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Tyrosine kinase inhibitors (TKIs) are the front-line therapy for chronic myeloid leukemia (CML), where phase 3 clinical trials have demonstrated their safety and efficacy. However, trial patients may not be representative of real-world patients (RWPs).</p><p><strong>Objective: </strong>To evaluate RWP clinical factors associated with effectiveness and safety in CML patients treated with TKIs.</p><p><strong>Methods: </strong>Patients with CML treated with at least 30 days of imatinib, dasatinib, nilotinib, or bosutinib between 2014 and 2018 were included. Patients were stratified into categories based on the number of factors that would have precluded enrollment into pivotal TKI phase 3 trials (0, 1, ≥2). End points included complete hematologic response (CHR), early molecular response (EMR), major molecular response (MMR), adverse event (AE)-induced dose decreases, treatment interruptions, and treatment discontinuations.</p><p><strong>Results: </strong>Final analyses included 174 patients. Patients with ≥2 factors had a higher risk of dose decreases (relative risk = 1.54; 95% CI = 1.02-2.34; <i>P</i> = 0.02) and a shorter time to dose decrease (hazard ratio = 2.43; 95% CI = 1.23-4.97; <i>P</i> = 0.006) compared with patients with 0 factors. Significant differences were observed in CHR at 1 month and MMR at 3 months between patients with 0 and ≥2 factors (<i>P</i> = 0.03 and <i>P</i> = 0.04, respectively).</p><p><strong>Conclusion and relevance: </strong>Approximately 60% of our RWPs would have been excluded from the pivotal phase 3 TKI trials. These data suggest that RWPs require more precise dosing to achieve CML clinical milestones and to mitigate AEs, but findings should be validated prospectively.</p>","PeriodicalId":512049,"journal":{"name":"The Annals of pharmacotherapy","volume":" ","pages":"753-763"},"PeriodicalIF":0.0000,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Response to Tyrosine Kinase Inhibitors in Real-World Patients With Chronic Myeloid Leukemia.\",\"authors\":\"Andy H Szeto, Tyler Bucci, Allison Deal, Anqi Zhu, Majd Ahmad, Amanda S Cass, Margaret R Sketch, Ryan Kemper, Joshua F Zeidner, Matthew C Foster, Benyam Muluneh, Daniel J Crona\",\"doi\":\"10.1177/10600280211044160\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Tyrosine kinase inhibitors (TKIs) are the front-line therapy for chronic myeloid leukemia (CML), where phase 3 clinical trials have demonstrated their safety and efficacy. However, trial patients may not be representative of real-world patients (RWPs).</p><p><strong>Objective: </strong>To evaluate RWP clinical factors associated with effectiveness and safety in CML patients treated with TKIs.</p><p><strong>Methods: </strong>Patients with CML treated with at least 30 days of imatinib, dasatinib, nilotinib, or bosutinib between 2014 and 2018 were included. Patients were stratified into categories based on the number of factors that would have precluded enrollment into pivotal TKI phase 3 trials (0, 1, ≥2). End points included complete hematologic response (CHR), early molecular response (EMR), major molecular response (MMR), adverse event (AE)-induced dose decreases, treatment interruptions, and treatment discontinuations.</p><p><strong>Results: </strong>Final analyses included 174 patients. Patients with ≥2 factors had a higher risk of dose decreases (relative risk = 1.54; 95% CI = 1.02-2.34; <i>P</i> = 0.02) and a shorter time to dose decrease (hazard ratio = 2.43; 95% CI = 1.23-4.97; <i>P</i> = 0.006) compared with patients with 0 factors. Significant differences were observed in CHR at 1 month and MMR at 3 months between patients with 0 and ≥2 factors (<i>P</i> = 0.03 and <i>P</i> = 0.04, respectively).</p><p><strong>Conclusion and relevance: </strong>Approximately 60% of our RWPs would have been excluded from the pivotal phase 3 TKI trials. These data suggest that RWPs require more precise dosing to achieve CML clinical milestones and to mitigate AEs, but findings should be validated prospectively.</p>\",\"PeriodicalId\":512049,\"journal\":{\"name\":\"The Annals of pharmacotherapy\",\"volume\":\" \",\"pages\":\"753-763\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The Annals of pharmacotherapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/10600280211044160\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2021/9/18 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Annals of pharmacotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/10600280211044160","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2021/9/18 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 1
摘要
背景:酪氨酸激酶抑制剂(TKIs)是慢性髓性白血病(CML)的一线治疗药物,其3期临床试验已经证明了其安全性和有效性。然而,试验患者可能不能代表现实世界的患者(RWPs)。目的:评价与TKIs治疗CML患者有效性和安全性相关的RWP临床因素。方法:纳入2014年至2018年期间接受伊马替尼、达沙替尼、尼洛替尼或博舒替尼治疗至少30天的CML患者。将患者根据妨碍纳入关键TKI 3期试验的因素数量(0、1、≥2)进行分类。终点包括完全血液学反应(CHR)、早期分子反应(EMR)、主要分子反应(MMR)、不良事件(AE)引起的剂量减少、治疗中断和停止治疗。结果:最终分析纳入174例患者。≥2个因素的患者减少剂量的风险较高(相对风险= 1.54;95% ci = 1.02-2.34;P = 0.02)和较短的剂量减少时间(风险比= 2.43;95% ci = 1.23-4.97;P = 0.006)。0和≥2个因素患者1个月CHR和3个月MMR差异有统计学意义(P = 0.03和P = 0.04)。结论和相关性:大约60%的RWPs将被排除在关键的3期TKI试验之外。这些数据表明,RWPs需要更精确的剂量来达到CML临床里程碑并减轻ae,但研究结果应进行前瞻性验证。
Response to Tyrosine Kinase Inhibitors in Real-World Patients With Chronic Myeloid Leukemia.
Background: Tyrosine kinase inhibitors (TKIs) are the front-line therapy for chronic myeloid leukemia (CML), where phase 3 clinical trials have demonstrated their safety and efficacy. However, trial patients may not be representative of real-world patients (RWPs).
Objective: To evaluate RWP clinical factors associated with effectiveness and safety in CML patients treated with TKIs.
Methods: Patients with CML treated with at least 30 days of imatinib, dasatinib, nilotinib, or bosutinib between 2014 and 2018 were included. Patients were stratified into categories based on the number of factors that would have precluded enrollment into pivotal TKI phase 3 trials (0, 1, ≥2). End points included complete hematologic response (CHR), early molecular response (EMR), major molecular response (MMR), adverse event (AE)-induced dose decreases, treatment interruptions, and treatment discontinuations.
Results: Final analyses included 174 patients. Patients with ≥2 factors had a higher risk of dose decreases (relative risk = 1.54; 95% CI = 1.02-2.34; P = 0.02) and a shorter time to dose decrease (hazard ratio = 2.43; 95% CI = 1.23-4.97; P = 0.006) compared with patients with 0 factors. Significant differences were observed in CHR at 1 month and MMR at 3 months between patients with 0 and ≥2 factors (P = 0.03 and P = 0.04, respectively).
Conclusion and relevance: Approximately 60% of our RWPs would have been excluded from the pivotal phase 3 TKI trials. These data suggest that RWPs require more precise dosing to achieve CML clinical milestones and to mitigate AEs, but findings should be validated prospectively.