我们调查了波纳替尼在慢性期慢性髓细胞白血病（CML-CP）真实世界的挽救治疗中的疗效。在连续的55例复发/难治CML-CP患者（中位年龄49岁）中，有35例（64%）失败了≥3个酪氨酸激酶抑制剂（TKI），35例（64%）在替尼替尼之前接受过治疗，14例（28%）患有ABL1T315I。在波纳替尼开始治疗时（中位剂量30mg/天），40名患者已达到完全血液学（CHR）缓解，4名达到完全细胞遗传学（CCyR）缓解，3名达到主要分子遗传学（MMR）缓解，而8名未能达到CHR（NR）。波纳替尼改善了13名CHR患者中的反应程度（33%），3名CCyR患者中的反应程度（75%），2名MMR患者中的反应程度（66%）和4名NR患者中的反应程度（50%）（p = 0.02）。在中位随访42个月的时间里，记录了13例（23%）死亡，5例（9%）爆发转化和25例（45%）异基因移植。使用波纳替尼后的5/10年生存率分别为77%/58%，当患者按异基因移植（p = 0.94），波纳替尼诱导的更深的反应（p = 0.28）或波纳替尼后的≥CCyR与CHR缓解状态（p = 0.25）分类时，并没有显著差异。ABL1T315I对生存不利（p = 0.04），但似乎不影响反应。替尼替尼之前暴露会增加动脉阻塞性事件（AOE）的风险（11% vs 0%；年龄调整p = 0.04）。波纳替尼开始/维持剂量（45 vs 15mg/天）不影响治疗反应或AOE。我们的观察结果支持在复发/难治CML-CP中使用较低的波纳替尼开始/维持剂量，但更深入的反应并没有明显的生存优势，治疗可能无法克服ABL1T315I对生存的不利影响。替尼替尼之前的暴露与波纳替尼后AOE的风险增加之间的关联需要进一步验证。©2023 Springer Nature Limited.

We surveyed the performance of ponatinib, as salvage therapy, in a real-world setting of chronic phase chronic myeloid leukemia (CML-CP). Among 55 consecutive patients (median age 49 years) with relapsed/refractory CML-CP, 35 (64%) had failed ≥3 tyrosine kinase inhibitors (TKIs), 35 (64%) were pre-treated with nilotinib, and 14 (28%) harbored ABL1T315I. At start of ponatinib (median dose 30 mg/day), 40 patients were already in complete hematologic (CHR), 4 in complete cytogenetic (CCyR), 3 in major molecular (MMR) remission, while 8 had not achieved CHR (NR). Ponatinib improved the depth of response in 13 (33%), 3 (75%), 2 (66%), and 4 (50%) patients with CHR, CCyR, MMR, and NR, respectively (p = 0.02). At a median follow-up of 42 months, 13 (23%) deaths, 5 (9%) blast transformations, and 25 (45%) allogeneic transplants were recorded. Five/10-year post-ponatinib survival was 77%/58% with no significant difference when patients were stratified by allogeneic transplant (p = 0.94), ponatinib-induced deeper response (p = 0.28), or a post-ponatinib ≥CCyR vs CHR remission state (p = 0.25). ABL1T315I was detrimental to survival (p = 0.04) but did not appear to affect response. Prior exposure to nilotinib was associated with higher risk of arterial occlusive events (AOEs; 11% vs 0%; age-adjusted p = 0.04). Ponatinib starting/maintenance dose (45 vs 15 mg/day) did not influence either treatment response or AOEs. Our observations support the use of a lower starting/maintenance dose for ponatinib in relapsed/refractory CML-CP but a survival advantage for deeper responses was not apparent and treatment might not overcome the detrimental impact of ABL1T315I on survival. The association between prior exposure to nilotinib and a higher risk of post-ponatinib AOEs requires further validation.© 2023. Springer Nature Limited.