Ponatinib 是第三代 BCR::ABL1 酪氨酸激酶抑制剂 (TKI)，对费城染色体阳性白血病具有强大的活性。在此，我们报告了ponatinib治疗慢性粒细胞白血病慢性期2期试验的长期随访情况。患者接受ponatinib 30至45 mg/天。主要终点是 6 个月完全细胞遗传学缓解率 (CCyR)。该研究于2014年6月进行，因存在心血管毒性风险，要求患者更换TKI。51名患者接受ponatinib（中位剂量，45 mg/天）治疗。中位年龄为 48 岁（范围：21-75 岁）； 30 名（59%）有基线心血管合并症。中位治疗持续时间为 13 个月（范围 2-25）。 14 名患者 (28%) 因毒性而停用普纳替尼，其中 36 名患者 (71%) 在美国食品和药物管理局警告/研究结束后停用，还有 1 名患者因不遵守规定而停用。达沙替尼是最常选择的二线 TKI（n = 34；66%）。在 6 个月时可评估的 46 名患者中，44 名 (96%) 达到 CCyR，37 名 (80%) 达到主要分子缓解，28 名 (61%) 达到 MR4，21 名 (46%) 达到 MR4.5。 CCyR、主要分子缓解、MR4 和 MR4.5 的 6 个月累计发生率分别为 96%、78%、50% 和 36%。分别有 67% 和 51% 的患者观察到持久 MR4 ≥24 或 ≥60 个月。 24 个月无事件生存率为 97%。中位随访128个月后，10年总生存率为90%。 8 名患者 (16%) 出现严重的 2 至 3 级心血管不良事件，导致 5 名患者 (10%) 永久停药。帕纳替尼在新诊断的慢性粒细胞白血病慢性期中产生了高细胞遗传学和分子反应。它在前线环境中的使用受到动脉/血管闭塞和其他严重毒性的阻碍。© 2024 美国癌症协会。

Ponatinib is a third-generation BCR::ABL1 tyrosine kinase inhibitor (TKI) with robust activity in Philadelphia chromosome-positive leukemias. Herein, we report the long-term follow-up of the phase 2 trial of ponatinib in chronic myeloid leukemia in chronic phase.Patients received ponatinib 30 to 45 mg/day. The primary end point was the rate of 6-month complete cytogenetic response (CCyR). The study was held in June 2014 because of the risk of cardiovascular toxicity, requiring patients to change TKI.Fifty-one patients were treated with ponatinib (median dose, 45 mg/day). Median age was 48 years (range, 21-75); 30 (59%) had baseline cardiovascular comorbidities. Median treatment duration was 13 months (range, 2-25). Fourteen patients (28%) discontinued ponatinib because of toxicities, 36 (71%) after the Food and Drug Administration warning/study closure, and one for noncompliance. Dasatinib was the most frequently chosen second-line TKI (n = 34; 66%). Among 46 patients evaluable at 6 months, 44 (96%) achieved CCyR, 37 (80%) major molecular response, 28 (61%) MR4, and 21 (46%) MR4.5. The cumulative 6-month rates of CCyR, major molecular response, MR4, and MR4.5 were 96%, 78%, 50%, and 36%, respectively. Durable MR4 ≥24 or ≥60 months was observed in 67% and 51% of patients, respectively. The 24-month event-free survival rate was 97%. After a median follow-up of 128 months, the 10-year overall survival rate was 90%. Eight patients (16%) had serious grade 2 to 3 cardiovascular adverse events, leading to permanent discontinuation in five (10%).Ponatinib yielded high cytogenetic and molecular responses in newly diagnosed chronic myeloid leukemia in chronic phase. Its use in the frontline setting is hindered by arterio-/vaso-occlusive and other severe toxicities.© 2024 American Cancer Society.