понатиниб

Результаты применения асциминиба, первого аллостерического ингибитора BCR::ABL1-тирозинкиназы, у больных хроническим миелолейкозом со множественной резистентностью к предшествующей терапии

МИЕЛОИДНЫЕ ОПУХОЛИ , , , ,

А.Г. Туркина, Е.А. Кузьмина

ФГБУ «НМИЦ гематологии» Минздрава России, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167

Для переписки: Елена Андреевна Кузьмина, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167; тел.: +7(918)167-35-69; e-mail: 1110ekuzmina@gmail.com

Для цитирования: Туркина А.Г., Кузьмина Е.А. Результаты применения асциминиба, первого аллостерического ингибитора BCR::ABL1-тирозинкиназы, у больных хроническим миелолейкозом со множественной резистентностью к предшествующей терапии. Клиническая онкогематология. 2023;16(3):311–320.

DOI: 10.21320/2500-2139-2023-16-3-311-320

РЕФЕРАТ

В настоящее время существует острая необходимость разработки новых подходов к лечению с целью преодолеть резистентность и непереносимость нескольких линий терапии ингибиторами тирозинкиназ (ИТК) у больных хроническим миелолейкозом (ХМЛ). Асциминиб — первый в своем классе ингибитор ВCR::ABL1-тирозинкиназы, связывающийся с миристоиловым карманом (specifically targeting ABL myristoyl pocket — STAMP), показавший свою эффективность и безопасность у больных ХМЛ с предшествующей неудачей терапии ИТК, включая наблюдения с панрезистентной мутацией T315I в химерном гене BCR::ABL1. В настоящем обзоре представлена информация о механизме действия асциминиба, результатах как доклинических, так и клинических исследований I и III фаз. Благоприятный профиль сердечно-сосудистой токсичности асциминиба расширяет возможности его применения у пациентов с сопутствующими сердечно-сосудистыми заболеваниями. Асциминиб зарегистрирован к применению в Российской Федерации в январе 2023 г., в связи с чем алгоритмы лечения больных ХМЛ с неэффективностью или непереносимостью предшествующей терапии должны быть обновлены с учетом этой новой опции.

Ключевые слова: хронический миелолейкоз, ингибиторы тирозинкиназ, STAMP-ингибиторы, асциминиб, понатиниб, мутация T315I.

Получено: 7 апреля 2023 г.

Принято в печать: 15 июня 2023 г.

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Статистика Plumx русский

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Роль селективности ингибиторов тирозинкиназ в развитии побочных эффектов при терапии хронического миелолейкоза

ОБЗОРЫ , , , , , , , , , , , , , ,

А.А. Зейфман1,2, Е.Ю. Челышева3, А.Г. Туркина3, Г.Г. Чилов1,2

1 ФГБУ «Институт органической химии им. Н.Д. Зелинского РАН», Москва, Российская Федерация

2 ООО «Фьюжн Фарма», Москва, Российская Федерация

3 ФГБУ «Гематологический научный центр» МЗ РФ, Москва, Российская Федерация

РЕФЕРАТ

В обзоре рассмотрен вопрос о связи селективности ингибиторов Bcr-Abl-киназ со спектром нежелательных побочных эффектов у больных хроническим миелолейкозом при проведении терапии. Суммированы данные по структуре и естественным биохимическим функциям наиболее хорошо изученных побочных мишеней ингибиторов Bcr-Abl-киназ: BRAF, FMS, EGFR, PDGFR, PYK2, TIE2, VEGFR1/2/3, а также оценена возможная связь их нецелевого ингибирования и нежелательных побочных эффектов ингибиторов тирозинкиназ.

Ключевые слова: хронический миелолейкоз, ингибиторы тирозинкиназ, селективность, иматиниб, нилотиниб, дазатиниб, понатиниб, PF-114, BRAF, FMS, EGFR, PDGFR, PYK2, TIE2, VEGFR1/2/3.

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