This retrospective chart review study investigated the clinical burden of adult patients with chronic-phase chronic myeloid leukemia (CP-CML) treated at three centers in France (2006–2021) who failed on two or more tyrosine kinase inhibitors (TKIs; third-line [3L]+ cohort) or harbored theBCR::ABL1T315I mutation (T315I cohort). In the 3L+ cohort (N = 157; median age at diagnosis, 56 years), TKIs received in 3L (median duration: 17 months) were dasatinib (32%), nilotinib (19%), imatinib (18%), ponatinib (17%), and bosutinib (14%). Of the 145 patients with documented responses in 3L, 42% experienced major molecular response (MMR) at 12 months. Median event-free survival [95% confidence interval] was 53.6 [44.0, 67.5] months, and median progression-free survival and overall survival (OS) were not reached. Achieving MMR in 3L was associated with a decreased mortality risk. In the T315I cohort (N = 17; 52 years), 41% of patients received five or more lines of therapy. Following identification of the T315I mutation, ponatinib was the most common TKI used (59%); the median [interquartile range] OS was 5 [3–10] years. The most common adverse events were infections (3L+ cohort) and thrombocytopenia (T315I cohort) (both 18%). Well-tolerated therapies that achieve durable responses are needed in 3L or earlier to improve CP-CML prognosis.
本回顾性病历审查研究调查了法国三家中心（2006–2021年）收治的慢性期慢性髓系白血病（CP-CML）成人患者的临床负担，这些患者曾对两种或以上酪氨酸激酶抑制剂（TKIs）治疗失败（三线及以上[3L+]队列）或携带BCR::ABL1 T315I突变（T315I队列）。在3L+队列（N=157；诊断时中位年龄56岁）中，三线治疗使用（中位持续时间：17个月）的TKIs包括达沙替尼（32%）、尼洛替尼（19%）、伊马替尼（18%）、普纳替尼（17%）和博舒替尼（14%）。在145例有三线治疗记录应答的患者中，42%在12个月时达到主要分子学反应（MMR）。中位无事件生存期[95%置信区间]为53.6[44.0, 67.5]个月，中位无进展生存期和总生存期（OS）尚未达到。三线治疗达到MMR与死亡风险降低相关。在T315I队列（N=17；中位年龄52岁）中，41%的患者接受了五线或以上治疗。在检测到T315I突变后，最常用的TKI是普纳替尼（59%）；中位[四分位距]OS为5[3–10]年。最常见的不良事件为感染（3L+队列）和血小板减少症（T315I队列）（均为18%）。为改善CP-CML预后，需要在三线或更早阶段采用能够实现持久应答且耐受性良好的治疗方案。
肿瘤(癌症)患者之家