Hayashino Kenta, Mochizuki Naoya, Kawatsuki Akihiro, Fujiwara Yuki, Kobayashi Hiroki, Yamasaki Tomoko, Asano Takeru, Kubonishi Shiro, Hiramatsu Yasushi
Department of Hematology and Oncology, Japanese Red Cross Society Himeji Hospital, 1-12-1, Shimoteno, Himeji-shi, Hyogo, Japan.
Department of Hematology and Oncology, Okayama University Hospital, 2-5-1 Shikata, Okayama-shi, Okayama, Japan.
Int J Hematol. 2025 Jul 22. doi: 10.1007/s12185-025-04041-w.
Tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of patients with chronic myeloid leukemia (CML). However, few patients maintain remission after discontinuing TKIs, and most require long-term treatment. Prolonged use of TKIs is associated with an increased risk of cardiovascular events (CVEs), particularly in patients with pre-existing cardiovascular comorbidities. We present the case of a 37-year-old man with a decade-long history of severe dilated cardiomyopathy that responded inadequately to standard pharmacologic management, who was under consideration for heart transplantation. Following a diagnosis of CML, the patient experienced various CVEs with TKIs, including dasatinib, bosutinib, imatinib, and nilotinib. These agents were discontinued, and treatment was switched to asciminib, a novel agent that targets the myristoyl pocket of the BCR::ABL1 protein distinct from the ATP-binding site targeted by conventional TKIs. This treatment was well tolerated without any CVEs. Given its minimal off-target activity and lower reported incidence of CVEs, asciminib may offer a viable and safer therapeutic option for CML patients with advanced cardiovascular comorbidities, including those awaiting heart transplantation.
酪氨酸激酶抑制剂(TKIs)显著改善了慢性髓性白血病(CML)患者的预后。然而,很少有患者在停用TKIs后仍能维持缓解状态,大多数患者需要长期治疗。长期使用TKIs与心血管事件(CVEs)风险增加相关,尤其是在已有心血管合并症的患者中。我们报告了一例37岁男性患者,他有长达十年的严重扩张型心肌病病史,对标准药物治疗反应不佳,正在考虑进行心脏移植。在诊断为CML后,该患者使用包括达沙替尼、博舒替尼、伊马替尼和尼洛替尼在内的TKIs时发生了各种CVEs。这些药物被停用,治疗改为阿塞西尼布,这是一种新型药物,靶向BCR::ABL1蛋白的肉豆蔻酰口袋,不同于传统TKIs靶向的ATP结合位点。这种治疗耐受性良好,未发生任何CVEs。鉴于其脱靶活性极小且报道的CVEs发生率较低,阿塞西尼布可能为患有晚期心血管合并症的CML患者,包括那些等待心脏移植的患者,提供一种可行且更安全的治疗选择。