Dataset Information

Comparative arrhythmia patterns among patients on tyrosine kinase inhibitors.

ABSTRACT:

Background

Tyrosine kinase inhibitors (TKIs) are widely used in the treatment of hematologic malignancies. Limited studies have shown an association between treatment-limiting arrhythmias and TKI, particularly ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor. We sought to comprehensively assess the arrhythmia burden in patients receiving ibrutinib vs non-BTK TKI vs non-TKI therapies.

Methods

We performed a retrospective analysis of consecutive patients who received long-term cardiac event monitors while on ibrutinib, non-BTK TKIs, or non-TKI therapy for a hematologic malignancy between 2014 and 2022.

Results

One hundred ninety-three patients with hematologic malignancies were included (ibrutinib = 72, non-BTK TKI = 46, non-TKI therapy = 75). The average duration of TKI therapy was 32 months in the ibrutinib group vs 64 months in the non-BTK TKI group (p = 0.003). The ibrutinib group had a higher prevalence of atrial fibrillation (n = 32 [44%]) compared to the non-BTK TKI (n = 7 [15%], p = 0.001) and non-TKI (n = 15 [20%], p = 0.002) groups. Similarly, the prevalence of non-sustained ventricular tachycardia was higher in the ibrutinib group (n = 31, 43%) than the non-BTK TKI (n = 8 [17%], p = 0.004) and non-TKI groups (n = 20 [27%], p = 0.04). TKI therapy was held in 25% (n = 18) of patients on ibrutinib vs 4% (n = 2) on non-BTK TKIs (p = 0.005) secondary to arrhythmias.

Conclusions

In this large retrospective analysis of patients with hematologic malignancies, patients receiving ibrutinib had a higher prevalence of atrial and ventricular arrhythmias compared to those receiving other TKI, with a higher rate of treatment interruption due to arrhythmias.

SUBMITTER: Wei C

PROVIDER: S-EPMC10851950 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Publications

Comparative arrhythmia patterns among patients on tyrosine kinase inhibitors.

Wei Chen C Fazal Muhammad M Loh Alexander A Kapoor Ridhima R Gomez Sofia Elena SE Shah Shayena S Rogers Albert J AJ Narayan Sanjiv M SM Wang Paul J PJ Witteles Ronald M RM Perino Alexander C AC Cheng Paul P Rhee June-Wha JW Baykaner Tina T

Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing 20230531 1

<h4>Background</h4>Tyrosine kinase inhibitors (TKIs) are widely used in the treatment of hematologic malignancies. Limited studies have shown an association between treatment-limiting arrhythmias and TKI, particularly ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor. We sought to comprehensively assess the arrhythmia burden in patients receiving ibrutinib vs non-BTK TKI vs non-TKI therapies.<h4>Methods</h4>We performed a retrospective analysis of consecutive patients who received long-term ...[more]

PMID: 37256462

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Project description:An important pathogenetic distinction in the classification of myeloproliferative neoplasms (MPNs) is the presence or absence of the BCR-ABL fusion gene, which encodes a unique oncogenic tyrosine kinase. The BCR-ABL fusion, caused by the formation of the Philadelphia chromosome (Ph) through translocation, constitutes the disease-initiating event in chronic myeloid leukemia. The development of successive BCR-ABL-targeted tyrosine-kinase inhibitors has led to greatly improved outcomes in patients with chronic myeloid leukemia, including high rates of complete hematologic, cytogenetic, and molecular responses. Such levels of treatment success have long been elusive for patients with Ph-negative MPNs, because of the difficulties in identifying specific driver proteins suitable as drug targets. However, in recent years an improved understanding of the complex pathobiology of classic Ph-negative MPNs, characterized by variable, overlapping multimutation profiles, has prompted the development of better and more broadly targeted (to pathway rather than protein) treatment options, particularly JAK inhibitors. In classic Ph-negative MPNs, overactivation of JAK-dependent signaling pathways is a central pathogenic mechanism, and mutually exclusive mutations in JAK2, MPL, and CALR linked to aberrant JAK activation are now recognized as key drivers of disease progression in myelofibrosis (MF). In clinical trials, the JAK1/JAK2 inhibitor ruxolitinib - the first therapy approved for MF worldwide - improved disease-related splenomegaly and symptoms independent of JAK2 (V617F) mutational status, and prolonged survival compared with placebo or standard therapy in patients with advanced MF. In separate trials, ruxolitinib also provided comprehensive hematologic control in patients with another Ph-negative MPN - polycythemia vera. However, complete cytogenetic or molecular responses with JAK inhibitors alone are normally not observed, underscoring the need for novel combination therapies of JAK inhibitors and complementary agents that better address the complexity of the pathobiology of classic Ph-negative MPNs. Here, we discuss the role of tyrosine-kinase inhibitors in the current MPN-treatment landscape.

Project description:BackgroundSeveral epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) have been approved for first-line (1L) treatment of EGFR-mutated metastatic non-small cell lung cancer (mNSCLC) in the United States (US). Real-world analyses of 1L treatment patterns with EGFR TKIs, including the third-generation EGFR TKI osimertinib which was most recently approved in 2018, are still sparse.MethodsThis retrospective observational study used data from IQVIA's prescription claims (LRx) and medical claims (Dx) databases. mNSCLC patients newly treated with any EGFR TKI in the 1L setting were identified from January 1, 2015 to April 30, 2020; the first date of EGFR TKI (third-generation osimertinib, first-generation [erlotinib, gefitinib], or second-generation [afatinib, dacomitinib]) was the index date. Treatment patterns were reported in the cohorts stratified by 1L EGFR TKI.ResultsA total of 2505 patients were included in the study (982 osimertinib, 1060 first-generation, and 463 second-generation EGFR TKI). Beginning in 2018, osimertinib became the most common 1L EGFR TKI (66.7%) and in early 2020, it accounted for 90.6% of 1L EGFR TKIs. Nearly all patients (>97%) were treated with 1L EGFR TKI monotherapy. Patients with 1L osimertinib had longer treatment duration compared to patients with 1L first- or second-generation EGFR TKI (median months: 17.8 vs. 8.7 vs. 10.5, respectively; log-rank test for comparisons with osimertinib p < 0.0001) over median follow-up times of 9.8, 20.5, and 19.3 months. 32.5% and 36.3% of the first- and second-generation EGFR TKI cohorts, respectively, had evidence of 2L treatment. Osimertinib monotherapy accounted for the majority of 2L treatments (58.3%/60.7%) and 11.3%/8.9% had 2L chemotherapy or immuno-oncology therapy following 1L first- or second-generation EGFR TKI.ConclusionIn this real-world study of a US claims database, 1L treatment duration was longer with osimertinib compared with other EGFR TKIs. Future studies with longer follow-up are recommended to understand treatment patterns after progression on EGFR TKIs.

Dataset Information

Comparative arrhythmia patterns among patients on tyrosine kinase inhibitors.

Background

Methods

Results

Conclusions

Publications

Comparative arrhythmia patterns among patients on tyrosine kinase inhibitors.

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