Помалидомид в терапии рецидивирующей/рефрактерной множественной миеломы

Семочкин С.В. Помалидомид в терапии рецидивирующей/рефрактерной множественной миеломы. Современная Онкология. 2023;25(2):159–166. DOI: 10.26442/18151434.2023.2.202255

© ООО «КОНСИЛИУМ МЕДИКУМ», 2023 г.

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Semochkin SV. Pomalidomide in the management of relapsed/refractory multiple myeloma: A review. Journal of Modern Oncology. 2023;25(2):159–166. DOI: 10.26442/18151434.2023.2.202255

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Аннотация

Помалидомид – иммуномодулирующий препарат III генерации, занявший прочное место в терапии рецидивирующей и/или рефрактерной множественной миеломы, в том числе у пациентов с устойчивостью к леналидомиду (R). Синергизм противоопухолевого действия получен при комбинировании помалидомида с дексаметазоном (схема Pd), ингибиторами протеасом и моноклональными антителами, направленными против рецепторов CD38 и SLAMF7. Дозолимитирующей токсичностью помалидомида является нейтропения. Данные по фармакокинетике указывают на существование прямой корреляции между опухолевой нагрузкой и концентрацией помалидомида в тканях. Преодоление резистентности к R рассматривается в качестве ключевого преимущества помалидомида при разработке триплетов, которые можно использовать во 2-й и последующих линиях лечения рецидивирующей и/или рефрактерной множественной миеломы. В исследовании 3-й фазы OPTIMISMM было 70% пациентов с устойчивостью к R. Рандомизацию проводили на терапию VPd (бортезомиб-Pd) и Vd (бортезомиб, дексаметазон). Схема Vd в качестве контроля реализована еще в двух близких исследованиях 3-й фазы ENDЕAVOR (карфилзомиб, дексаметазон – Kd) и CASTOR (даратумумаб, Vd – DVd). Применительно к выборке пациентов с резистентностью к R медиана выживаемости без прогрессирования в исследовании OPTIMISMM для триплета VPd составила 9,5 мес, в CASTOR для DVd – 9,3 мес и в ENDEAVOR для Kd – 8,6 мес. В исследовании ICARIA-MM (фаза 3, резистентность к R – 94%) доказано преимущество включения в триплет изутаксимаба – Isa (медиана выживаемости без прогрессирования – 11,1 мес для Isa-Pd и 5,9 мес для Pd; p<0,0001). Близкие данные получены в ходе проведения исследования ELOQUENT-3 (фаза 2, резистентность к R – 90%) другого моноклонального антитела – элотузумаба – E (10,3 мес – EPd против 4,7 мес – Pd; p=0,008). В исследовании APOLLO (фаза 3, резистентность к R – 80%) подтверждена эффективность триплета с даратумумабом – D (12,4 мес – DPd против 6,9 мес – Pd; p=0,0018). Акцент в данном литературном обзоре сделан на рассмотрении схем лечения, имеющих актуальное прикладное значение для клинической практики в России.

Ключевые слова: множественная миелома, иммуномодулирующие препараты, леналидомид, помалидомид

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Pomalidomide is a third-generation immunomodulatory drug that has taken an important place in the management of relapsed/refractory multiple myeloma including in patients with resistance to lenalidomide (R). Synergism of antitumor activity was obtained by combining pomalidomide with dexamethasone (Pd), proteasome inhibitors, and monoclonal antibodies directed against CD38 and SLAMF7 receptors. The dose-limiting toxicity of pomalidomide is neutropenia (48–60% grade ≥3 for a dose of 4 mg/day). Overcoming resistance to R is seen as a key benefit of pomalidomide in the development of triplets that can be used in 2nd and subsequent lines of relapsed/refractory multiple myeloma treatment. In OPTIMISMM study (phase III), 70% of patients were R resistant. Randomization was performed on VPd (bortezomib-Pd) and Vd (bortezomib, dexamethasone) therapy. Vd as control was implemented in two related phases III trials ENDEAVOR (carfilzomib, dexamethasone) and CASTOR (daratumumab-Vd). For patients with resistance to R, the median progression-free survival was 9.5 mon for VPd in OPTIMISMM; 9.3 mon in CASTOR (resistant to R 21%) for DVd, and 9.3 mon in ENDEAVOR (21%) for Kd – 8.6 mon. The ICARIA-MM study (phase 3, resistance to R – 94%) demonstrated the benefit of incorporating isutaximab into the triplet (median progression-free survival 11.1 and 5.9 mon for Isa-Pd and Pd respectively; p<0.0001). Similar data were obtained in the ELOQUENT-3 study (phase II, resistance to R – 90%) for elotuzumab (10.3 and 4.7 mon for EPd and Pd respectively; p=0.008). In the APOLLO study (phase III, resistance to R – 80%), the efficacy of the triplet with daratumumab was confirmed (12.4 and 6.9 mon for DPd and Pd respectively; p=0.0018). In the present review, the focus is on the consideration of treatment regimens that are of relevance to Russian clinical practice.

Keywords: multiple myeloma, immunomodulatory drugs, lenalidomide, pomalidomide

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Авторы

С.В. Семочкин*

1 Московский научно-исследовательский онкологический институт им. П.А. Герцена –
филиал ФГБУ «НМИЦ радиологии» Минздрава России, Москва, Россия;
2 ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия
*semochkin_sv@rsmu.ru

________________________________________________

Sergey V. Semochkin*

1 Hertsen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre, Moscow, Russia;
2 Pirogov Russian National Research Medical University, Moscow, Russia
*semochkin_sv@rsmu.ru

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