Abstract

The introduction of orally available tyrosine kinase inhibitors (TKI) into the treatment of chronic myeloid leukemia (CML) 25 years ago has substantially improved the clinical outcome of affected patients and resulted in a near-normal life expectancy in chronic phase (CP). Despite of a significant fraction of currently about one third of newly diagnosed CP patients eventually reaching treatment-free remission, the majority of patients still remain on life-long treatment with TKIs. Therefore, a profound knowledge of TKI-related side effects including an increased sensitivity for organ systems predominantly involved, grading, kinetics, duration and reversibility, class-effects versus compound-relatedness as well as a better understanding of how particularly long-lasting, chronic, sometimes formally low-grade toxicities can actually significantly impair patient's self-assessed quality of life is of utmost importance for an adequate patient/doctor relationship. Given that nowadays, severity and degree of preexisting comorbidities might predict long-term survival of individual patients more significantly than the underlying CML itself, it becomes most important to properly and thoroughly select the TKI of choice on this basis as well as on the individually required co-medications. Given the variety of 2nd, 3rd and now allosteric TKIs available for the molecular targeting of the disease-driving BCR-ABL oncogene in addition to the "class-defining" Imatinib, personalization of CML therapy should now be further extended towards a better appreciation of comorbidities and co-medications before selection of an individual's TKI treatment complemented by a long-term oriented, patient-centered management and prevention of (sometimes irreversible) TKI side effects.

Full Text
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