Tyrosine Kinase Inhibitors for the Treatment of Chronic-Phase Chronic Myeloid Leukemia: Long-Term Patient Care and Management

Abstract

Several tyrosine kinase inhibitors (TKIs) are now approved for the treatment of chronic myeloid leukemia in chronic phase. The efficacy of these drugs has been repeatedly demonstrated, as has their tolerability in most patients. However, late and chronic toxicities become an important issue for many patients facing long-term TKI exposure. For patients on long-term imatinib, gastrointestinal events, fluid retention, muscle cramps, fatigue, and hepatotoxicity are among the most common and most clinically relevant adverse events (AEs). A few of these have also emerged as important AEs with some of the newer TKIs. Distinct long-term toxicity concerns have emerged for dasatinib (pleural effusion, pulmonary hypertension, headache, and dyspnea) and nilotinib (rash, headache, myalgia, alopecia, and hyperglycemia), whereas due to the recent approval of bosutinib and ponatinib, their long-term toxicity profiles have not been fully characterized. Clinical experience with each of these drugs is accumulating, and ensuring proper adherence and monitoring for potential AEs is essential for effective treatment.

PTEN‐AKT pathway attenuates apoptosis and adverse remodeling in ponatinib‐induced skeletal muscle toxicity following BMP‐7 treatment

“…Ponatinib is a third generation tyrosine kinase inhibitor (TKI), used for various types of cancer therapies such as leukemia, lung cancer, and glioblastoma (Gozgit et al, 2012 ; Luciano et al, 2020 ; Tan et al, 2019 ; Zhang et al, 2014 ). However, clinical utilization of TKIs is associated with several adverse toxicities in various organs including cardiovascular, hepatic, and gastrointestinal (Bauer et al, 2016 ; Shah et al, 2013 ). Ponatinib‐induced cardiotoxicity has recently been shown to activate apoptosis in cardiomyocytes and causes cardiac dysfunction (Casavecchia et al, 2020 ; Chan et al, 2020 ; Ma et al, 2020 ; Singh et al, 2019 ; Talbert et al, 2015 ).…”

Fluid retention-associated adverse events in patients treated with BCR::ABL1 inhibitors based on FDA Adverse Event Reporting System (FAERS): a retrospective pharmacovigilance study

“…These agents are generally well tolerated as they have a favourable toxicity profile compared with traditional chemotherapy regimens, but their potent and specific adverse events (AEs) should also be closely monitored 6. The safety profiles of BCR::ABL inhibitors as we know include fluid retention, pulmonary, cardiovascular, haematological and gastrointestinal-related AEs 8 9. Due to strict study entry criteria, relatively small sample sizes and limited follow-up time, clinical trial data may not reflect the full profile of AEs with BCR::ABL inhibitors.…”