Блинатумомаб в терапии острого лимфобластного лейкоза: Российское многоцентровое исследование

С.Н. Бондаренко1, Е.Н. Паровичникова2, А.А. Масчан3, О.Ю. Баранова4, Т.В. Шелехова5, В.А. Доронин6, В.Я. Мельниченко7, К.Д. Капланов8, О.С. Успенская9, А.Н. Соколов2, Н.В. Мякова3, И.С. Моисеев1, И.В. Маркова1, Е.И. Дарская1, А.Г. Смирнова1, Т.А. Быкова1, Б.И. Аюбова1, И.А. Самородова1, Е.В. Бабенко1, И.М. Бархатов1, Т.Л. Гиндина1, А.Д. Кулагин1, Б.В. Афанасьев1

1 НИИ детской онкологии, гематологии и трансплантологии им. Р.М. Горбачевой, ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова», ул. Льва Толстого, д. 6/8, Санкт-Петербург, Российская Федерация, 197022

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

3 ФГБУ «НМИЦ детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России, ул. Саморы Машела, д. 1, Москва, Российская Федерация, 117997

4 ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 24, Москва, Российская Федерация, 115478

5 ФГБОУ ВО «Саратовский государственный медицинский университет им. В.И. Разумовского» Минздрава России, ул. Большая Казачья, д. 112, Саратов, Российская Федерация, 410012

6 ГБУЗ «Городская клиническая больница № 40 ДЗМ», ул. Касаткина, д. 7, Москва, Российская Федерация, 129301

7 ФГБУ «Национальный медико-хирургический центр им. Н.И. Пирогова», Минздрава России, ул. Нижняя Первомайская, д. 70, Москва, Российская Федерация, 105203

8 ГБУЗ «Волгоградский областной клинический онкологический диспансер», ул. Землячки, д. 78, Волгоград, Российская Федерация, 400138

9 ГБУЗ «Ленинградская областная клиническая больница», пр-т Луначарского, д. 45–49, Санкт-Петербург, Российская Федерация, 194291

Для переписки: Сергей Николаевич Бондаренко, канд. мед. наук, ул. Льва Толстого, д. 6/8, Санкт-Петербург, Российская Федерация, 197022; тел.: +7(812)338-62-72; e-mail: dr.sergeybondarenko@gmail.com

Для цитирования: Бондаренко С.Н., Паровичникова Е.Н., Масчан А.А. и др. Блинатумомаб в терапии острого лимфобластного лейкоза: Российское многоцентровое исследование. Клиническая онкогематология. 2019;12(2):145–53.

DOI: 10.21320/2500-2139-2019-12-2-145-153


РЕФЕРАТ

Актуальность. Успехи в терапии рецидивов и рефрактерного острого лимфобластного лейкоза (Р/Р ОЛЛ) в последние годы связаны с внедрением методов иммунотерапии, в т. ч. биспецифического активатора собственных T-клеток пациента блинатумомаба (Блинцито™, Амджен®) (БЦ).

Цель. Оценить эффективность и токсичность БЦ в лечении пациентов с Р/Р ОЛЛ и с персистенцией минимального опухолевого клона до и после трансплантации аллогенных гемопоэтических стволовых клеток (аллоТГСК).

Материалы и методы. В исследование включено 66 больных В-ОЛЛ CD19+ в возрасте 18–72 лет, из них 23 (35 %) с определяемой минимальной остаточной болезнью (МОБ+) и 43 (65 %) с Р/Р ОЛЛ. У 18 (27 %) пациентов терапия БЦ проводилась после предшествующей аллоТГСК.

Результаты. В общей группе 2-летние общая (ОВ) и безрецидивная выживаемость (БРВ) пациентов, ответивших на терапию БЦ, составили 53 и 38 %. При Р/Р ОЛЛ полные ремиссии (ПР) достигнуты у 29 (67 %) пациентов, в т. ч. у 24 (83 %) с отрицательной МОБ. Частота ПР была выше в группе стандартного цитогенетического риска по сравнению с группой высокого риска — 73 и 59 % соответственно. При уровне бластных клеток в костном мозге менее или более 50 % частота ПР составила 85 и 61 % соответственно. Частота ПР при использовании БЦ после предшествующей аллоТГСК и без таковой оказалась 80 и 60 % соответственно. У пациентов с Р/Р ОЛЛ, ответивших на терапию БЦ, 2-летние ОВ и БРВ были 40 и 26 % соответственно, в группе МОБ+ ОЛЛ — 66 и 51 % соответственно. Частота рецидивов была меньше в группе с аллоТГСК, чем без таковой, — 21 vs 55 %. Нежелательные явления III–IV степени отмечались у 25 (38 %) пациентов. У 11 (16 %) больных потребовалось прервать введение БЦ, у 5 (7 %) — терапия была прекращена досрочно.

Заключение. Эффективность БЦ выше в группе МОБ+, а также у больных Р/Р ОЛЛ с меньшей опухолевой массой. Использование БЦ после аллоТГСК позволяет достичь ремиссии у большинства пациентов и может сочетаться с иммуноадоптивной терапией.

Ключевые слова: острый лимфобластный лейкоз, таргетная терапия, блинатумомаб.

Получено: 22 августа 2018 г.

Принято в печать: 18 января 2019 г.

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ЛИТЕРАТУРА

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Биспецифические антитела в клинике и клинических исследованиях (обзор литературы)

О.Н. Солопова, В.А. Мисюрин

ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 24, Москва, Российская Федерация, 115478

Для переписки: Всеволод Андреевич Мисюрин, канд. биол. наук, Каширское ш., д. 24, Moсква, Российская Федерация, 115478; тел. +7(985)436-30-19; e-mail: vsevolod.misyurin@gmail.com

Для цитирования: Солопова О.Н., Мисюрин В.А. Биспецифические антитела в клинике и клинических исследованиях (обзор литературы). Клиническая онкогематология. 2019;12(2):125–44.

DOI: 10.21320/2500-2139-2019-12-2-125-144


РЕФЕРАТ

Лечебные моноклональные антитела давно уже стали важным инструментом в руках врачей разных специальностей, прежде всего онкологов. Появление биспецифических антител открыло новые горизонты для лечения рака, стало возможным привлечение собственного иммунитета пациента к борьбе с опухолью. В данном обзоре рассматриваются все форматы и стратегии, использованные при разработке биспецифических антител, дошедших до стадии клинических исследований, а также доступные результаты этих клинических исследований.

Ключевые слова: биспецифические антитела, блинатумомаб, катумаксомаб, эмицизумаб, клиническое исследование.

Получено: 13 августа 2018 г.

Принято в печать: 22 января 2019 г.

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