Comorbidities and outcomes of patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: a real-world, nationwide, retrospective study from Hungary

Purpose: This study aimed to provide real-world evidence on the characteristics, treatment patterns, and outcomes of patients with chronic myeloid leukemia (CML) receiving tyrosine kinase inhibitor (TKI) treatment in Hungary between 2011 and 2019.Patients and methods: This nationwide, retrospective study included patients who were newly diagnosed with CML in Hungarian clinical practice between January 2011 and December 2019. The analysis was based on the reimbursed prescription claims for imatinib, bosutinib, dasatinib, nilotinib, or ponatinib with the ICD-10 code C9210 in a public pharmacy between January 2009 and December 2019 using data from the National Health Insurance Fund (NHIF) of Hungary. CML incidence and prevalence, TKI treatment patterns, comorbidities, and overall survival (OS) were examined.Results: Between 2011 and 2019, altogether 1,407 patients were diagnosed with CML, with an annual average of 156 patients. The number of patients newly initiating first-line TKI therapy for CML significantly increased between 2011 and 2019 (2011: n = 136 vs. 2019: n = 191; p = 0.0043). Nilotinib was typically prescribed for younger patients (≤64 years), while older patients (≥65 years) mostly received imatinib. The most common comorbidity of CML patients was hypertension, and the proportion of patients with other malignancies was relatively high in all treatment groups. 5-year OS was 77.1% during the whole study period. Patients initiating first-line TKI treatment for CML in 2015 had significantly better 4-year OS compared to those starting treatment in 2011 (82.4% vs. 73.5%, respectively, (HR 0.53 (95%CI 0.32–0.87) p = 0.0118).Conclusion: This study is the first to provide insights into the characteristics, treatment patterns, and outcomes of CML patients treated with TKIs in Hungarian clinical practice between 2011 and 2019. We found slightly lower OS rates compared to other European countries, however, there was a statistically significant improvement in 4-year OS during the study period. The management of CML was in line with international guidelines and recommendations

DataSheet1_Comorbidities and outcomes of patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: a real-world, nationwide, retrospective study from Hungary.docx

Purpose: This study aimed to provide real-world evidence on the characteristics, treatment patterns, and outcomes of patients with chronic myeloid leukemia (CML) receiving tyrosine kinase inhibitor (TKI) treatment in Hungary between 2011 and 2019.Patients and methods: This nationwide, retrospective study included patients who were newly diagnosed with CML in Hungarian clinical practice between January 2011 and December 2019. The analysis was based on the reimbursed prescription claims for imatinib, bosutinib, dasatinib, nilotinib, or ponatinib with the ICD-10 code C9210 in a public pharmacy between January 2009 and December 2019 using data from the National Health Insurance Fund (NHIF) of Hungary. CML incidence and prevalence, TKI treatment patterns, comorbidities, and overall survival (OS) were examined.Results: Between 2011 and 2019, altogether 1,407 patients were diagnosed with CML, with an annual average of 156 patients. The number of patients newly initiating first-line TKI therapy for CML significantly increased between 2011 and 2019 (2011: n = 136 vs. 2019: n = 191; p = 0.0043). Nilotinib was typically prescribed for younger patients (≤64 years), while older patients (≥65 years) mostly received imatinib. The most common comorbidity of CML patients was hypertension, and the proportion of patients with other malignancies was relatively high in all treatment groups. 5-year OS was 77.1% during the whole study period. Patients initiating first-line TKI treatment for CML in 2015 had significantly better 4-year OS compared to those starting treatment in 2011 (82.4% vs. 73.5%, respectively, (HR 0.53 (95%CI 0.32–0.87) p = 0.0118).Conclusion: This study is the first to provide insights into the characteristics, treatment patterns, and outcomes of CML patients treated with TKIs in Hungarian clinical practice between 2011 and 2019. We found slightly lower OS rates compared to other European countries, however, there was a statistically significant improvement in 4-year OS during the study period. The management of CML was in line with international guidelines and recommendations.</p

Dasatinib inhibits coated-platelet generation in patients with chronic myeloid leukemia

Since the introduction of tyrosine kinase inhibitors, the overall survival of patients with chronic myeloid leukemia has markedly improved. However long term use of these drugs results in various adverse events. Treatment with second generation dasatinib is often complicated by hemorrhagic events. Previous lumi-aggregometry studies have shown impaired platelet function in patients on dasatinib therapy. Dual agonist activated platelets (coated-platelets) are also sensitive indicators of platelet function. We hypothesized that dual activation with convulxin and thrombin of platelets in a flow cytometric assay could be a more sensitive method for detecting platelet dysfunction as compared to single agonist studies used in lumi-aggregometer. Platelets of healthy volunteers incubated with dasatinib as well as platelets from patients on dasatinib therapy were investigated. Low therapeutic plasma level dasatinib concentrations at which a considerable reduction in coated-platelet generation was observed in vitro, did not cause detectable change in platelet aggregation response. Coated-platelet assay and lumi-aggregometry were also investigated at 0, 1 and 4 hours after drug administration in dasatinib treated CML patients. Significant decrease was observed at 1 hour in maximal aggregation by collagen. Although the aggregation curves became normalized by 4 hours, coated-platelet generation was still inhibited in dasatinib treated patients. Nilotinib, another second generation tyrosine kinase inhibitor, had no effect on aggregation and on coated-platelet formation neither in vitro nor in ex vivo samples. At therapeutic plasma levels coated-platelet assay is more sensitive than lumi-aggregometry studies for the demonstration of the inhibitory effect of dasatinib on platelet function