Variability in the molecular response to frontline tyrosine kinase inhibitor (TKI) therapy in chronic myeloid leukemia may be partially driven by differences in the level of kinase inhibition induced. We measured in vivo BCR::ABL1 kinase inhibition (IVKI) in circulating mononuclear cells after 7 days of therapy. In 173 patients on imatinib 600 mg/day, 23% had low IVKI (<11% reduction in kinase activity from baseline); this was associated with higher rates of early molecular response (EMR) failure; lower rates of major molecular response (MMR), and MR4.5 by 36 months, compared to high IVKI patients. Low IVKI was more common (39%) in patients with large spleens (≥10 cm by palpation). Notably 55% of patients with large spleens and low IVKI experienced EMR failure whereas the EMR failure rate in patients with large spleens and high IVKI was only 12% (p = 0.014). Furthermore, patients with large spleen and low IVKI had a higher incidence of blast crisis, inferior MMR, MR4.5, and event-free survival compared to patients with large spleen and high IVKI and remaining patients. In nilotinib-treated patients (n = 73), only 4% had low IVKI. The combination of low IVKI and large spleen is associated with markedly inferior outcomes and interventions in this setting warrant further studies.
慢性髓性白血病中对一线酪氨酸激酶抑制剂（TKI）治疗的分子反应变异性，可能部分由诱导的激酶抑制水平差异所驱动。我们在治疗7天后测量了循环单核细胞中的体内BCR::ABL1激酶抑制（IVKI）。在173名接受伊马替尼600毫克/日治疗的患者中，23%的患者IVKI较低（激酶活性较基线降低<11%）；与高IVKI患者相比，这与较高的早期分子反应（EMR）失败率、较低的主要分子反应（MMR）率和36个月时的MR4.5率相关。在脾脏肿大（触诊≥10厘米）的患者中，低IVKI更为常见（39%）。值得注意的是，脾脏肿大且低IVKI的患者中有55%经历了EMR失败，而脾脏肿大且高IVKI患者的EMR失败率仅为12%（p=0.014）。此外，与脾脏肿大且高IVKI的患者及其他患者相比，脾脏肿大且低IVKI的患者急变期发生率更高，MMR、MR4.5和无事件生存期更差。在尼洛替尼治疗的患者（n=73）中，仅4%有低IVKI。低IVKI与脾脏肿大的组合与显著较差的预后相关，针对此情况的干预措施值得进一步研究。
肿瘤(癌症)患者之家