酪氨酸激酶抑制剂（TKI）疗法极大地改善了慢性粒细胞性白血病（CML）患者的预后，将慢性期（CP）CML患者的生存期望值提高到普通人群的水平。然而，尽管取得了这些进展，近50%的CP CML患者未能对一线治疗做出反应，大多数患者未能对随后的二线TKI做出反应。缺乏针对失败二线治疗患者的治疗指南。本研究旨在确定TKI作为第三线治疗在“真实世界”的临床实践中的疗效，并确定有利影响疗效的因素。我们回顾性分析了100名患有CP CML的患者的病历。患者的中位年龄为51岁（范围21-88岁），其中36%为男性。第三线TKI治疗的中位持续时间为22（范围1-147）个月。总体而言，完全细胞遗传学反应（CCyR）的实现率为35%。在四个不同基线反应水平的患者组中，在第三线治疗基线的任何CyR组中均取得了最佳结果。因此，15/15名和8/16名（50%）部分细胞遗传学反应（PCyR）或最小或轻微的细胞遗传学反应（mmCyR）患者均达到CCyR，而在基线没有任何CyR的69名患者中只检测到了12/69名患者的CCyR（p < 0.001）。单变量回归分析显示，第三线TKI治疗中与CCyR实现负相关的因素是一线或二线TKI治疗中没有任何CyR（p < 0.001）、第三线TKI之前没有CHR（p = 0.003）和第三线TKI之前没有任何CyR（p < 0.001）。在治疗开始到最后一次就诊的中位观察时间[56（4-180）个月]内，27%的病例进展为加速期或爆发期CML，32%的患者死亡。与没有CCyR的组相比，在第三线治疗中具有CCyR的患者的无进展生存期（PFS）和总生存期（OS）显著提高。最后就诊时，第三线TKI疗法仍在18%的患者中继续进行，治疗暴露时间的中位数为58（范围6-140）个月；这些患者中83%具有稳定和持久的CCyR，这表明基线没有CHR且第三线TKI至少在12个月内没有CCyR的患者应该成为同基因干细胞移植、第三代TKI或实验性疗法的候选者。版权所有©2023 Chitanava、Matvienko、Shuvaev、Voloshin、Martynkevich、Vlasova、Efremova、Mileeva、Pirkhalo、Makarova、Vlasik、Karyagina、Il`ina、Medvedeva、Dorofeeva、Shneider、Siordiya、Kulemina、Sbityakova、Lazorko、Alexeeva、Motorin、Morozova和Lomaia。

Tyrosine kinase inhibitor (TKI) therapy has greatly improved the prognosis of patients with chronic myeloid leukemia (CML), improving the survival expectancy of patients with chronic phase (CP) CML to that of the general population. However, despite these advances, nearly 50% of patients with CP CML experience failure to respond to frontline therapy, and most fail to respond to the subsequent second-line TKI. Treatment guidelines for patients failing second-line therapy are lacking. This study aimed to determine the efficacy of TKIs as third-line therapy in a "real-world" clinical practice setting and identify factors favorably influencing the long-term outcomes of therapy.We have retrospectively analyzed the medical records of 100 patients with CP CML.The median age of the patients was 51 (range, 21-88) years, and 36% of the patients were men. The median duration of the third-line TKI therapy was 22 (range, 1- 147) months. Overall, the rate of achieving complete cytogenetic response (CCyR) was 35%. Among the four patient groups with different levels of responses at baseline, the best results were achieved in the groups with any CyR at the baseline of third-line therapy. Thus, СCyR was reached in all 15 and 8/ 16 (50%) patients with partial cytogenetic response (PCyR) or minimal or minor CyR (mmCyR), respectively, whereas CCyR was detected only in 12/69 (17%) patients without any CyR at baseline (p < 0.001). Univariate regression analysis revealed that the factors negatively associated with CCyR achievement in thirdline TKI therapy were the absence of any CyR on first- or second-line TKI therapy (p < 0.001), absence of CHR prior to third-line TKI (p = 0.003), and absence of any CyR prior to third-line TKI (p < 0.001). During the median observation time from treatment initiation to the last visit [56 (4-180) months], 27% of cases progressed into accelerated phase or blast phase CML, and 32% of patients died.Progression-free survival (PFS) and overall survival (OS) were significantly higher in patients with CCyR on third-line than in the group without CCyR on third-line therapy. At the last visit, third-line TKI therapy was ongoing in 18% of patients, with a median time of treatment exposure of 58 (range, 6-140) months; 83% of these patients had stable and durable CCyR, suggesting that patients without CHR at baseline and without CCyR at least by 12 months on third-line TKI should be candidates for allogeneic stem cell transplantation, third-generation TKIs, or experimental therapies.Copyright © 2023 Chitanava, Matvienko, Shuvaev, Voloshin, Martynkevich, Vlasova, Efremova, Mileeva, Pirkhalo, Makarova, Vlasik, Karyagina, Il`ina, Medvedeva, Dorofeeva, Shneider, Siordiya, Kulemina, Sbityakova, Lazorko, Alexeeva, Motorin, Morozova and Lomaia.