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.
我们在真实世界中评估了普纳替尼作为挽救疗法在慢性髓性白血病慢性期(CML-CP)患者中的疗效。连续入组的55例复发/难治性CML-CP患者(中位年龄49岁)中，35例(64%)曾对≥3种酪氨酸激酶抑制剂(TKI)治疗无效，35例(64%)曾接受尼洛替尼治疗，14例(28%)携带ABL1T315I突变。开始普纳替尼治疗时(中位剂量30mg/天)，40例患者已达完全血液学缓解(CHR)，4例达完全细胞遗传学缓解(CCyR)，3例达主要分子学缓解(MMR)，8例未达CHR(NR)。普纳替尼分别使13例(33%)CHR患者、3例(75%)CCyR患者、2例(66%)MMR患者和4例(50%)NR患者的缓解深度得到改善(p=0.02)。中位随访42个月期间，记录到13例(23%)死亡、5例(9%)急变转化和25例(45%)异基因移植。普纳替尼治疗后5年/10年生存率为77%/58%，按异基因移植(p=0.94)、普纳替尼诱导的深度缓解(p=0.28)或治疗后≥CCyR与CHR缓解状态(p=0.25)分层时均无显著差异。ABL1T315I突变对生存不利(p=0.04)但似乎不影响治疗反应。既往尼洛替尼暴露与更高的动脉闭塞事件(AOEs)风险相关(11% vs 0%；年龄校正后p=0.04)。普纳替尼起始/维持剂量(45mg/天 vs 15mg/天)对治疗反应或AOEs均无影响。我们的观察支持在复发/难治性CML-CP中使用较低起始/维持剂量的普纳替尼，但深度缓解并未显现明确的生存优势，且治疗可能无法克服ABL1T315I突变对生存的不利影响。既往尼洛替尼暴露与普纳替尼治疗后较高AOEs风险的关联仍需进一步验证。
肿瘤(癌症)患者之家