medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2023-362medsovet-7984Research ArticleОНКОГЕМАТОЛОГИЯONCOHEMATOLOGY25-летний опыт лечения хронического миелолейкоза ингибиторами тирозинкиназ: результаты, возможности, вопросы25 years of experience in the treatment of chronic myeloid leukemia with tyrosine kinase inhibitors: results, opportunities, questionshttps://orcid.org/0000-0001-7816-808XЦыбаН. Н.TsybaN. N.

Цыба Николай Николаевич - д.м.н., аналитик 1-й категории отдела диагностики и лечения гематологических заболеваний.

125167, Москва, Новый Зыковский проезд, д. 4

Nikolay N. Tsyba - Dr. Sci. (Med.), 1st Category Analyst, Department of Diagnostics and Treatment of Hematological Diseases, National Research Center for Hematology.

4, Novyy Zykovskiy Proezd, Moscow, 125167

tsyba2007@ya.ruhttps://orcid.org/0000-0001-9947-2371ТуркинаА. Г.TurkinaA. G.

Туркина Анна Григорьевна - д.м.н., профессор, заведующий научно-консультативным отделением химиотерапии миелопролиферативных заболеваний.

125167, Москва, Новый Зыковский проезд, д. 4

Anna G. Turkina - Dr. Sci. (Med.), Professor, Head of the Scientific Advisory Department of Chemotherapy for Myeloproliferative Diseases, National Research Center for Hematology.

4, Novyy Zykovskiy Proezd, Moscow, 125167

turkianna@yandex.ruНациональный медицинский исследовательский центр гематологииРоссияNational Research Center for HematologyRussian Federation20231701202402289100Copyright © Цыба Н.Н., Туркина А.Г., 20242024Цыба Н.Н., Туркина А.Г.Tsyba N.N., Turkina A.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/7984

Проведен анализ данных об эффективности терапии хронического миелолейкоза (ХМЛ) ингибиторами тирозинкиназ и ряда положений, требующих обсуждения и возможного пересмотра на современном этапе. Первые же клинические исследования иматиниба – первого АТФ-конкурентного ингибитора BCR::ABL1, начатые в 1998 г., продемонстрировали чрезвычайно высокую терапевтическую эффективность, впечатляюще увеличившую показатели безрецидивной и общей выживаемости больных ХМЛ. Продолжительность жизни подавляющего числа пациентов стала сравнимой с продолжительностью жизни основной популяции. За прошедшие годы арсенал терапевтических средств для лечения ХМЛ значительно обогатился: созданы и одобрены к применению три АТФ-конкурентных ингибитора тирозинкиназ 2-го поколения, для лечения пациентов с мутацией Т315I зарегистрированы два препарата 3-го поколения – понатиниб и первый аллостерический ингибитор тирозинкиназ асциминиб. Регулярный цитогенетический и молекулярно-генетический мониторинг позволяет адекватно оценивать объем лейкозного клона и является неотъемлемой частью оценки эффективности терапии, позволяя контролировать и сохранять у ряда пациентов состояние ремиссии без применения ингибиторов тирозинкиназ. Сегодня иматиниб остается ключевым препаратом 1-й линии терапии, в то же время назначение ингибиторов тирозинкиназ 2-го поколения в 1-й линии терапии может привести к достижению более раннего и глубокого ответа. Выбор препарата для каждого конкретного пациента с учетом наилучшей переносимости и максимальной эффективности позволяет индивидуализировать лечение и расширить возможности терапии.

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.

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The authors declare that there are no conflicts of interest present.