Mohanavelu Prahathishree, Mutnick Mira, Mehra Nidhi, White Brandon, Kudrimoti Sparsh, Hernandez Kluesner Kaci, Chen Xinyu, Nguyen Tim, Horlander Elaina, Thenot Helena, Kota Vamsi, Mitchell Cassie S
Laboratory for Pathology Dynamics, Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332, USA.
Hematology and Oncology, Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA.
Cancers (Basel). 2021 Apr 1;13(7):1643. doi: 10.3390/cancers13071643.
Tyrosine kinase inhibitors (TKIs) are the frontline therapy for BCR-ABL (Ph+) chronic myeloid leukemia (CML). A systematic meta-analysis of 43 peer-reviewed studies with 10,769 CML patients compared the incidence of gastrointestinal adverse events (GI AEs) in a large heterogeneous CML population as a function of TKI type. Incidence and severity of nausea, vomiting, and diarrhea were assessed for imatinib, dasatinib, bosutinib, and nilotinib. Examination of combined TKI average GI AE incidence found diarrhea most prevalent (22.5%), followed by nausea (20.6%), and vomiting (12.9%). Other TKI GI AEs included constipation (9.2%), abdominal pain (7.6%), gastrointestinal hemorrhage (3.5%), and pancreatitis (2.2%). Mean GI AE incidence was significantly different between TKIs ( < 0.001): bosutinib (52.9%), imatinib (24.2%), dasatinib (20.4%), and nilotinib (9.1%). Diarrhea was the most prevalent GI AE with bosutinib (79.2%) and dasatinib (28.1%), whereas nausea was most prevalent with imatinib (33.0%) and nilotinib (13.2%). Incidence of grade 3 or 4 severe GI AEs was ≤3% except severe diarrhea with bosutinib (9.5%). Unsupervised clustering revealed treatment efficacy measured by the complete cytogenetic response, major molecular response, and overall survival is driven most by disease severity, not TKI type. For patients with chronic phase CML without resistance, optimal TKI selection should consider TKI AE profile, comorbidities, and lifestyle.
酪氨酸激酶抑制剂（TKIs）是BCR-ABL（Ph+）慢性髓性白血病（CML）的一线治疗药物。一项对43项经同行评审的研究（涉及10769例CML患者）进行的系统荟萃分析，比较了在一个大型异质性CML人群中，胃肠道不良事件（GI AEs）的发生率与TKI类型的关系。评估了伊马替尼、达沙替尼、博舒替尼和尼洛替尼引起的恶心、呕吐和腹泻的发生率及严重程度。对联合TKI的平均GI AE发生率进行检查发现，腹泻最为常见（22.5%），其次是恶心（20.6%）和呕吐（12.9%）。其他TKI引起的GI AE包括便秘（9.2%）、腹痛（7.6%）、胃肠道出血（3.5%）和胰腺炎（2.2%）。不同TKI之间的平均GI AE发生率存在显著差异（<0.001）：博舒替尼（52.9%）、伊马替尼（24.2%）、达沙替尼（20.4%）和尼洛替尼（9.1%）。腹泻是博舒替尼（79.2%）和达沙替尼（28.1%）最常见的GI AE，而恶心在伊马替尼（33.0%）和尼洛替尼（13.2%）中最为常见。除博舒替尼引起的严重腹泻（9.5%）外，3级或4级严重GI AE的发生率≤3%。无监督聚类分析显示，通过完全细胞遗传学反应、主要分子反应和总生存率衡量的治疗效果主要由疾病严重程度驱动，而非TKI类型。对于无耐药性的慢性期CML患者，最佳TKI选择应考虑TKI的AE谱、合并症和生活方式。
