Adverse outcomes in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: Follow‐up of patients diagnosed 2002–2017 in a complete coverage and nationwide agnostic register study

Abstract

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

Evaluation of Time to Onset and Outcome of Cardiac Adverse Events Associated with Nilotinib using Post-Marketing Surveillance

“…As for cardiac failure, the Weibull distribution showed that the incidence developed early after nilotinib administration, representing a finding consistent with results from previous pharmacovigilance analysis and clinical trials [3, 5, 30, 32]. Clinicians thus need to be alert to the onset of symptoms of cardiac failure right from the initial stages of nilotinib treatment.…”

Determinants of frontline tyrosine kinase inhibitor choice for patients with chronic‐phase chronic myeloid leukemia: A study from the Registro Italiano LMC and Campus CML

“…In a study from The University of Texas MD Anderson Cancer Center in 531 patients with CML treated with different TKIs, 237 patients (45%) developed cardiovascular events and, among them, hypertension was seen in 175 (74%) 21 . A real‐life Swedish study on 1238 TKI‐treated patients diagnosed with CP‐CML between 2002 and 2017 showed an increased incidence ratio (IRR) of morbidity compared to matched healthy controls, with a significantly higher risk in patients treated with nilotinib or dasatinib, mainly for acute myocardial infarction (IRR, 2.9 for nilotinib), chronic ischemic heart disease (IRR, 2.2 for nilotinib), pleural effusion (IRR, 11.6 for dasatinib), and upper respiratory infections (IRR, 3.0 for dasatinib) 22 …”

Adverse reactions after treatment with dasatinib in chronic myeloid leukemia: Characteristics, potential mechanisms, and clinical management strategies

“…Previous studies demonstrated that dasatinib was associated with lymphocytosis. Regarding the pharmacodynamic mechanism, dasatinib affects the ability to maintain pulmonary endothelial integrity in a dose-dependent manner by generating mitochondrial oxidative stress, inducing endothelial cell apoptosis, and impairing vascular permeability ( 100 , 101 ). Recently, it has been proposed that the development of dasatinib-related PE is associated with changes in intercellular connectivity and the production of stress fibers and reactive oxygen species in the cytoplasm ( 102 , 103 ).…”