Morita Kiyomi, Sasaki Koji
Department of Leukemia, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 428, Houston, TX, 77030, USA.
Int J Hematol. 2021 May;113(5):624-631. doi: 10.1007/s12185-021-03127-5. Epub 2021 Mar 29.
The advent of tyrosine kinase inhibitors (TKIs) has dramatically improved the outcome of patients with chronic myeloid leukemia (CML). Currently, four TKIs are available for the frontline treatment, including the first-generation TKI (imatinib) and the second-generation TKIs (dasatinib, nilotinib, and bosutinib). The second-generation TKIs lead to a faster and deeper molecular response without a survival benefit compared with imatinib. However, the opportunity for the treatment discontinuation and functional cure requires the achievement of durable deep molecular remission. Therefore, the second-generation TKIs should be considered as initial therapy for chronic-phase CML. Switch of therapy is warranted in case of treatment failure, including resistance and/or intolerance. The life expectancy of patients with CML is approaching that of the general population. Given an expected lifespan, future perspectives should consider the strategy for the optimal choice of TKIs, allowing for long-duration of effective TKI therapy with less toxicity to aim for a functional cure. A novel prediction approach such as artificial intelligence-driven analysis on the accumulated data from clinical trials paves a promising path for the personalized recommendation on frontline TKIs and precise survival prediction.
酪氨酸激酶抑制剂（TKIs）的出现显著改善了慢性髓性白血病（CML）患者的治疗结果。目前，有四种TKIs可用于一线治疗，包括第一代TKI（伊马替尼）和第二代TKIs（达沙替尼、尼洛替尼和博舒替尼）。与伊马替尼相比，第二代TKIs能带来更快、更深的分子反应，但无生存获益。然而，实现持久深度分子缓解是停止治疗并实现功能性治愈的必要条件。因此，第二代TKIs应被视为慢性期CML的初始治疗药物。如出现治疗失败，包括耐药和/或不耐受，则有必要更换治疗方案。CML患者的预期寿命正在接近普通人群。考虑到预期寿命，未来的研究方向应思考如何优化TKIs的选择策略，以实现长期有效的TKI治疗，同时降低毒性，从而实现功能性治愈。一种新的预测方法，如基于临床试验积累数据的人工智能驱动分析，为一线TKIs的个性化推荐和精确生存预测开辟了一条充满希望的道路。
