Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie - IBE, Medizinische Fakultät, LMU München, München, Germany.
ELN Foundation, Weinheim, Germany.
Leukemia. 2023 Nov;37(11):2231-2236. doi: 10.1038/s41375-023-02028-2. Epub 2023 Sep 19.
Therapy after failing response milestones in CML is controversial. Risks associated with comorbidities, drug toxicities or transplantation may preclude switching to another tyrosine kinase inhibitor (TKI) or other treatments. No information on long-term survival of failing patients is available. To systematically analyse survival after reaching, or not reaching, response milestones, 1342 patients from CML-study IV with newly diagnosed CML in chronic phase and regular molecular tests were studied. Landmark survival analyses were done by <0.1%, 0.1-1%, >1-10% and >10% BCR::ABL1 at 3, 6, 12 and 24 months up to 14 years. 10- to 12-year survival of patients who failed the failure milestones (>10% BCR::ABL1 at 6 months, >1% BCR::ABL1 at 12 months) ranged around 80%, 10% less than in responding patients. These results suggest revision of milestones. Age (more or less than 60 years) had no major impact on survival differences, but on hazard ratios and CML-specific survival. Switching to alternative therapies, which was observed in 26.9% of the patients, did not change the main results. The data show that TKI-treated patients not reaching failure milestones still may derive benefit from continuing TKI-treatment and provide a basis for individualised decisions, if failing patients are confronted with risks of alternative treatments.
在 CML 中失败的反应里程碑后进行治疗存在争议。与合并症、药物毒性或移植相关的风险可能会阻止患者转为另一种酪氨酸激酶抑制剂（TKI）或其他治疗方法。目前尚无关于失败患者长期生存的信息。为了系统地分析达到或未达到反应里程碑后的生存情况，对 CML-Study IV 中 1342 例新诊断为慢性期 CML 的患者进行了研究，这些患者定期进行分子检测。通过 landmark 生存分析，在 3、6、12 和 24 个月时，分别以<0.1%、0.1-1%、>1-10%和>10%BCR::ABL1 为终点，随访时间长达 14 年。在 6 个月时未能达到失败里程碑（BCR::ABL1>10%）、12 个月时未能达到失败里程碑（BCR::ABL1>1%）的患者，在 10 至 12 年内的生存率约为 80%，比有反应的患者低 10%。这些结果表明需要修订失败里程碑。年龄（大于或小于 60 岁）对生存差异没有重大影响，但对危险比和 CML 特异性生存有影响。26.9%的患者转换为替代治疗，这并没有改变主要结果。这些数据表明，未达到失败里程碑的 TKI 治疗患者可能仍然受益于继续 TKI 治疗，并为个体化决策提供了依据，如果失败患者面临替代治疗的风险。
