Pediatric Hematology/Oncology and Immunopathology

Вопросы гематологии/онкологии и иммунопатологии в педиатрии

1726-17082414-9314

Fund Doctors, Innovations, Science for Children

694

10.24287/1726-1708-2023-22-1-46-52

ORIGINAL ARTICLES

ОРИГИНАЛЬНЫЕ СТАТЬИ

The use of inotuzumab ozogamicin in children with relapsed/refractory B-lineage acute lymphoblastic leukemia

Опыт применения инотузумаба озогамицина у детей с рецидивами и рефрактерным течением В-линейного острого лимфобластного лейкоза

https://orcid.org/0000-0003-2801-7421

Evstratov

D. A.

Евстратов

Д. А.

Russian Federation

Dmitry A. Evstratov, a hematologist at the Oncohematology Department

1 Samory Mashela St., Moscow 117997, Russia

Евстратов Дмитрий Андреевич, врач-гематолог отделения онкогематологии

117997, Москва, ул. Саморы Машела, 1

Evstratov.D.A@yandex.ru

https://orcid.org/0000-0003-1814-6772

Shutova

A. D.

Шутова

А. Д.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-8725-7532

Dyakonova

Yu. Yu.

Дьяконова

Ю. Ю.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-7696-1153

Radygina

S. A.

Радыгина

С. А.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0001-5201-6475

Abugova

Yu. G.

Абугова

Ю. Г.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-3247-8688

Anderzhanova

L. Kh.

Андержанова

Л. Х.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0001-7959-3512

Vavilova

L. A.

Вавилова

Л. А.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-7461-0050

Litvinov

D. V.

Литвинов

Д. В.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-2322-5734

Novichkova

G. A.

Новичкова

Г. А.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-0889-6986

Popov

A. M.

Попов

А. М.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0003-2294-0821

Fominykh

V. V.

Фоминых

В. В.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0001-7265-0414

Khachatryan

L. A.

Хачатрян

Л. А.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0003-0520-5630

Shelikhova

L. N.

Шелихова

Л. Н.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-4779-1896

Myakova

N. V.

Мякова

Н. В.

Russian Federation

Moscow

Москва

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthсare of the Russian FederationФГБУ «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России

01032023

221

46522712202227022023

2023

«D. Rogachev NMRCPHOI»

ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России

https://creativecommons.org/licenses/by/4.0

https://hemoncim.com/jour/article/view/694

Today, treatment results for acute lymphoblastic leukemia (ALL) look encouraging, yet 10–15% patients still end up relapsing. The success of relapse treatment is directly dependent on whether or not a tumor clone has been completely eradicated before hematopoietic stem cell transplantation (HSCT). Immunotherapy made it possible to achieve minimal residual disease (MRD) – negative remission even in refractory patients. One example of such immunotherapeutic agents is inotuzumab ozogamicin (InO), an anti-CD22 monoclonal antibody conjugated to the cytotoxic agent calicheamicin. We included 17 patients under the age of 18 with relapsed or refractory precursor B-cell ALL (pre-B ALL) who had been treated with InO at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of Russia from 01.10.2016 to 01.09.2022. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The efficacy of the therapy was assessed based on the patients’ morphological response, MRD negativity and overall survival. Treatment toxicity was assessed according to CTCAE 5.0 (Common Terminology Criteria for Adverse Events). Statistical analysis was performed using the XLSTAT 2016 software. The majority of the patients (75%) responded to the therapy. MRD negativity was achieved in 41.2% of the study patients. The one-year overall survival rate was 40.3% (95% confidence interval 14.8–65.7). The treatment was well tolerated but 33% of the patients treated with standard-dose InO and subsequent HSCT developed veno-occlusive disease/sinusoidal obstruction syndrome. In our study, we demonstrated the high efficacy of InO both when used as a rescue therapy in patients with relapsed/refractory pre-B ALL and as a bridging therapy in patients before HSCT.

В настоящее время результаты терапии острого лимфобластного лейкоза (ОЛЛ) являются весьма обнадеживающими, но, несмотря на это, у 10–15% пациентов развивается рецидив заболевания. Успешное лечение рецидива зависит от полноты эрадикации опухолевого клона перед проведением трансплантации гемопоэтических стволовых клеток (ТГСК). Появление иммунотерапевтических агентов сделало возможным достижение ремиссии с отрицательной минимальной остаточной болезнью (МОБ) даже у пациентов, рефрактерных к химиотерапии. Примером такого препарата является конъюгат инотузумаб озогамицин (ИнО) – анти-CD22-моноклональное антитело, связанное с цитотоксическим агентом калихеамицином. В работу были включены 17 пациентов в возрасте до 18 лет с рецидивами или рефрактерными формами ОЛЛ из В-клеточных предшественников (ВП-ОЛЛ), получившие терапию ИнО в ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России с 01.10.2016 по 01.09.2022. Исследование одобрено независимым этическим комитетом и утверждено решением ученого совета НМИЦ ДГОИ им. Дмитрия Рогачева. Оценка эффективности терапии проводилась по морфологическому ответу, достижению МОБ-негативности и общей выживаемости. Анализ токсичности проводился согласно CTCAE 5.0 (Common Terminology Criteria for Adverse Events). Статистическая обработка выполнялась на программном обеспечении XLSTAT 2016. Ответ на терапию был зафиксирован в большинстве случаев (75%). Среди всех пациентов отрицательный МОБ-статус был достигнут в 41,2% случаев. Общая однолетняя выживаемость пациентов составила 40,3% (95% доверительный интервал 14,8–65,7). Токсичность препарата была приемлемой, однако стоит отметить развитие веноокклюзионной болезни печени/синдрома синусоидальной обструкции у 33% пациентов, получавших ИнО в стандартной дозе с последующей ТГСК. Данное исследование продемонстрировало достаточно высокую эффективность ИнО в качестве как терапии «спасения» у пациентов с рецидивами и рефрактерным течением ВП-ОЛЛ, так и «бридж-терапии» перед ТГСК.

acute lymphoblastic leukemiarelapsechildreninotuzumab ozogamicin

острый лимфобластный лейкозрецидивдетиинотузумаб озогамицин

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