BCR::ABL1酪氨酸激酶抑制剂（TKIs）已经改善了慢性髓细胞白血病（CML）患者的预后。在二代TKI（2G-TKI）失败后，对于慢性期CML（CML-CP）最佳的第三线治疗尚未完全确定。我们分析了在我们机构进行的、PACE和OPTIC试验中接受第三代BCR::ABL1 TKI治疗的354例CML-CP患者的情况，并评估了替代2 G-TKI或泊那汀尼后的结果。我们进行了倾向性得分匹配分析，以比较结果，并进行多变量分析以确定与生存相关的变量。173（49%）患者接受了2 G-TKI，181（51%）接受了泊那汀尼。泊那汀尼组中的患者有更多心血管风险因素（34%对19%）和更高的疾病负担（BCR::ABL1转录本水平> 1%，165/175 [94% ]比75/135 [55%]；p <.001），与2G-TKI组相比。在173例接受泊那汀尼治疗的可评估患者中，89例（52%）实现了基线转录本的2 + -log降低（20% 2-log降低和32% 3 + -log降低）。在128例接受2G-TKI治疗的可评估患者中，44例（34%）实现了基线转录本的2 + -log降低（13% 2-log降低和21% 3 + -log降低）。随着46个月的中位随访，2G-TKI的3年无进展生存率为59%（匹配前为60%），泊那汀尼的3年无进展生存率为83%（匹配前为81%）（p <.001）。2G-TKI的3年生存率为83%（匹配前为81%），泊那汀尼的3年生存率为87%（匹配前为89%）（p =.03）。通过多变量分析，使用泊那汀尼作为第三线治疗是与更好生存相关的唯一独立因素（p =.003）。总之，泊那汀尼是CML-CP患者在前两代TKI治疗失败后的最佳治疗方法。 © 2023 Wiley Periodicals LLC。

The BCR::ABL1 tyrosine kinase inhibitors (TKIs) have improved the outcomes of patients with chronic myeloid leukemia (CML). After failing second-generation TKI (2G-TKI), the optimal third-line therapy in chronic phase CML (CML-CP) is not well established. We analyzed 354 patients with CML-CP treated with a third-line BCR::ABL1 TKI at our institution, and in the PACE and OPTIC trials, and evaluated the outcome after alternate 2G-TKIs or ponatinib. We performed a propensity score matching analysis to compare outcomes and multivariate analysis to identify variables associated with survival. One hundred seventy-three (49%) patients received 2G-TKIs and 181 (51%) ponatinib. Patients in the ponatinib group had more cardiovascular risk factors (34% versus 19%) and higher disease burden (BCR::ABL1 transcript levels >1%, 165/175 [94%] versus 75/135 [55%]; p < .001) compared with the 2G-TKI group. Among the 173 evaluable patients treated with ponatinib, 89 (52%) achieved 2 + -log reduction of baseline transcripts (20% 2-log reduction and 32% 3 + -log reduction). Among the 128 evaluable patients treated with 2G-TKIs, 44 (34%) achieved 2 + -log reduction of baseline transcripts (13% 2-log reduction and 21% 3 + -log reduction). With a median follow-up of 46 months, the 3-year progression-free survival was 59% (60% before matching) with 2G-TKI and 83% (81% before matching) with ponatinib (p < .001). The 3-year survival was 83% (81% before matching) with 2G-TKI and 87% (89% before matching) with ponatinib (p = .03). By multivariate analysis, third-line therapy with ponatinib was the only independent factor associated with better survival (p = .003). In conclusion, ponatinib is an optimal treatment for patients with CML-CP failing two prior TKIs.© 2023 Wiley Periodicals LLC.