25 years of experience in the treatment of chronic myeloid leukemia with tyrosine kinase inhibitors: results, opportunities, questions

Abstract

More than 25 years ago, the discovery of imatinib, the first ATP-competitive inhibitor of BCR::ABL1, the driving oncoprotein of chronic myeloid leukemia, revolutionized patients life by transforming a fatal condition into a chronic disease. The review analyzes data on the effectiveness of chronic myeloid leukemia therapy with tyrosine kinase inhibitors and a number of provisions that require discussion and, possibly, revision at the present stage. The first clinical trials of imatinib, the first ATP- competitive inhibitor of BCR::ABL1, started in 1998, demonstrated extremely high therapeutic efficacy, impressively increasing the rates of relapse-free and overall survival in patients with chronic myeloid leukemia. The life expectancy of the overwhelming number of patients has become comparable to the life expectancy of the main population. Over the years, the arsenal of therapeutic agents for the treatment of chronic myeloid leukemia has been significantly enriched: three ATP-competitive tyrosine kinase inhibitors of the 2nd generation have been created and approved for use, 2 drugs of the 3rd generation: ponatinib, and the first allosteric tyrosine kinase inhibitor asciminib have been registered for the treatment of patients with the T315I mutation. Regular cytogenetic and molecular genetic monitoring makes it possible to adequately assess the volume of the leukemic clone and is an integral part of evaluating the effectiveness of therapy, allowing to control and maintain remission in a number of patients without the use of tyrosine kinase inhibitors. Today imatinib remains the key drug of the 1st line of therapy, at the same time, the appointment of 2nd generation tyrosine kinase inhibitors in the first line of therapy can lead to an earlier and deeper response. The choice of the drug for each individual patient, taking into account the best tolerability and maximum effectiveness, allows individualizing treatment and expanding the possibilities of therapy.