Перспективы применения иммуномодулирующих препаратов и модуляторов цереблон Е3-лигазы в лечении множественной миеломы

ОБЗОРЫ , , , , ,

С.В. Семочкин1,2

1 МНИОИ им. П.А. Герцена — филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2-й Боткинский пр-д, д. 3, Москва, Российская Федерация, 125284

2 ФГАОУ ВО «РНИМУ им. Н.И. Пирогова» Минздрава России, ул. Островитянова, д. 1, Москва, Российская Федерация, 117997

Для переписки: Сергей Вячеславович Семочкин, д-р мед. наук, профессор, 2-й Боткинский пр-д, д. 3, Москва, Российская Федерация, 125284; e-mail: semochkin_sv@rsmu.ru

Для цитирования: Семочкин С.В. Перспективы применения иммуномодулирующих препаратов и модуляторов цереблон Е3-лигазы в лечении множественной миеломы. Клиническая онкогематология. 2023;16(3):229–41.

DOI: 10.21320/2500-2139-2023-16-3-229-241

РЕФЕРАТ

За последние десятилетия прогресс в лечении множественной миеломы (ММ) связан с лучшим пониманием биологии этого заболевания и внедрением в практику новых классов лекарственных средств, таких как иммуномодулирующие препараты (IMiD), ингибиторы протеасом (ИП) и моноклональные антитела (МАТ). Современные IMiD (леналидомид, помалидомид) являются производными талидомида, которые, несмотря на сходство химической структуры, проявляют лишь относительную перекрестную резистентность. Леналидомид — иммуномодулятор 2-го поколения с высокой противоопухолевой активностью и благоприятным профилем безопасности. В 2006 г. применение леналидомида в комбинации с дексаметазоном (схема Rd) было одобрено FDA (США) для лечения рецидивов/рефрактерной MM, а через 9 лет, в 2015 г., — для впервые диагностированной ММ. В 2015–2019 гг. для лечения рецидивов MM были разработаны схемы, построенные на комбинации Rd с бортезомибом (VRd), карфилзомибом (KRd), иксазомибом (IRd), элотузумабом (ERd) и даратумумабом (DRd), — так называемые триплеты. Помалидомид — препарат 3-го поколения, используемый у пациентов с рефрактерностью к леналидомиду. Для лечения пациентов с рецидивами/рефрактерной ММ, которые получили не менее двух линий терапии, включавших леналидомид и бортезомиб, в практику внедрены схемы из трех препаратов на основе помалидомида и дексаметазона в комбинации с элотузумабом (EPd), изатуксимабом (Isa-Pd) и даратумумабом (DPd). В 2010 г. была открыта молекулярная мишень действия IMiD — белок цереблон (CRBN), входящий в ферментный комплекс CRBN E3-лигазы. Понимание данного механизма позволило создать новое семейство производных талидомида, получившее название модуляторов CRBN E3-лигазы (CELMoD). Два препарата этой группы (ибердомид, мезигдомид) в исследованиях I–II фазы продемонстрировали обнадеживающую активность при ММ с рефрактерностью к трем классам противоопухолевых препаратов (IMiD, ИП и анти-CD38 МАТ). Фокус представленного обзора направлен на проспективные исследования IMiD и CELMoD на разных этапах лечения ММ.

Ключевые слова: множественная миелома, иммуномодулирующие препараты, модуляторы цереблон Е3-лигазы, леналидомид, помалидомид, ибердомиб, мезигдомид.

Получено: 25 января 2023 г.

Принято в печать: 28 мая 2023 г.

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Статистика Plumx русский

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