Tyrosine kinase inhibitors (TKIs) have profoundly improved the clinical outcome for patients with chronic myeloid leukemia (CML), but their overall survival is still subnormal and the treatment is associated with adverse events. In a large cohort-study, we assessed the morbidity in 1328 Swedish CML chronic phase patients diagnosed 2002–2017 and treated with TKIs, as compared to that in carefully matched control individuals. Several Swedish patient registers with near-complete nationwide coverage were utilized for data acquisition. Median follow-up was 6 (IQR, 3–10) years with a total follow-up of 8510 person-years for the full cohort. Among 670 analyzed disease categories, the patient cohort showed a significantly increased risk in 142 while, strikingly, no category was more common in controls. Increased incidence rate ratios/IRR (95% CI) for more severe events among patients included acute myocardial infarction (AMI) 2.0 (1.5–2.6), heart failure 2.6 (2.2–3.2), pneumonia 2.8 (2.3–3.5), and unspecified sepsis 3.5 (2.6–4.7). When comparing patients on 2nd generation TKIs vs. imatinib in a within-cohort analysis, nilotinib generated elevated IRRs for AMI (2.9; 1.5–5.6) and chronic ischemic heart disease (2.2; 1.2–3.9), dasatinib for pleural effusion (11.6; 7.6–17.7) and infectious complications, for example, acute upper respiratory infections (3.0; 1.4–6.0). Our extensive real-world data reveal significant risk increases of severe morbidity in TKI-treated CML patients, as compared to matched controls, particularly for 2nd generation TKIs. Whether this increased morbidity may also translate into increased mortality, thus preventing CML patients to achieve a normalized overall survival, needs to be further explored.

中文翻译：

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接受酪氨酸激酶抑制剂治疗的慢性粒细胞白血病患者的不良后果：在完全覆盖和全国不可知登记研究中对 2002-2017 年诊断出的患者的随访

酪氨酸激酶抑制剂 (TKI) 显着改善了慢性粒细胞白血病 (CML) 患者的临床结果，但其总生存期仍低于正常水平，并且治疗与不良事件相关。在一项大型队列研究中，我们评估了 2002-2017 年诊断出并接受 TKI 治疗的 1328 名瑞典 CML 慢性期患者的发病率，与仔细匹配的对照个体相比。几个几乎覆盖全国的瑞典患者登记册被用于数据采集。中位随访时间为 6（IQR，3-10）年，整个队列的总随访时间为 8510 人年。在分析的 670 种疾病类别中，患者队列显示 142 种疾病的风险显着增加，而令人惊讶的是，没有类别在对照组中更常见。患者中更严重事件的发生率/IRR (95% CI) 增加包括急性心肌梗死 (AMI) 2.0 (1.5-2.6)、心力衰竭 2.6 (2.2-3.2)、肺炎 2.8 (2.3-3.5) 和未指定败血症 3.5 (2.6–4.7)。在队列内分析中比较第二代 TKI 与伊马替尼的患者时，尼罗替尼对 AMI（2.9；1.5-5.6）和慢性缺血性心脏病（2.2；1.2-3.9）产生升高的 IRR，达沙替尼用于胸腔积液（11.6； 7.6–17.7）和感染性并发症，例如急性上呼吸道感染（3.0；1.4–6.0）。我们广泛的真实世界数据显示，与匹配的对照相比，TKI 治疗的 CML 患者的严重发病风险显着增加，特别是对于第二代 TKI。这种增加的发病率是否也可能转化为增加的死亡率，