Adverse events and dose modifications of tyrosine kinase inhibitors in chronic myelogenous leukemia

Abstract

The prognosis of chronic myelogenous leukemia (CML-CP) in chronic phase has improved dramatically since the introduction of imatinib. In addition to imatinib, second- and third-generation tyrosine kinase inhibitors (TKIs) and a novel allosteric inhibitor, asciminib, are now available. During long-term TKI therapy, the optimal selection of TKI therapy for individual patients requires the understanding of specific patterns of toxicity profile to minimize chronic toxicity and the risk of adverse events, including pulmonary arterial hypertension, pleural effusion, and cardiovascular events. Given the high efficacy of TKI therapy, dose modifications of TKI therapy reduce the risk of toxicities and improves quality of life during therapy. In this review article, we summarize the characteristics and adverse event profile of each TKI and dose modifications in patients with CML-CP and discuss future perspectives in the treatment of CML-CP.

A New Algorithm Integrating Molecular Response, Toxicity, and Plasma Level Measures for Ponatinib Dose Choice in Patients Affected by Chronic Myeloid Leukemia

“…Nowadays, if a molecular response of at least 3 logs (MR3) [2] is achieved by the first 6 months of treatment, CML patients' survival is comparable to that of the general population [3]. Nevertheless, 33% of these patients presented at least one grade 3-4 adverse event, analogously to what was observed in CML, where 20-30% of cases fail to achieve therapeutic goals or develop intolerable side effects or resistance within the first three years of treatment [4,5].…”