Нилотиниб и дазатиниб в 1-й линии терапии больных хроническим миелолейкозом в хронической фазе

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Аннотация

Таргетная терапия иматинибом (ИМ) у большинства пациентов с хроническим миелолейкозом (ХМЛ) в хронической фазе (ХФ) приводит к стабильной гематологической и цитогенетической ремиссии. Тем не менее часть больных не достигают полного цитогенетического ответа (ПЦГО) или впоследствии его утрачивают. Кроме того, риск цитогенетического рецидива и прогрессии болезни в фазу акселерации (ФА), или бластный криз (БК) практически приближается к нулю при достижении большого молекулярного ответа (БМО), однако на фоне терапии иматинибом его получают всего около половины пациентов. Еще более редки случаи достижения полного молекулярного ответа (ПМО). Клинические исследования по применению новых ингибиторов тирозинкиназ (ИТК) нилотиниба и дазатиниба в ХФ ХМЛ в качестве 1-й линии терапии доказали их преимущество над ИМ в получении ПЦГО и БМО, а при применении нилотиниба также и по снижению риска трансформации в ФА/БК и увеличению общей выживаемости. В данной обзорной статье в основном приведены результаты двух многоцентровых международных клинических исследований под названиями ENESTnd (The Evaluating Nilotinib Efficacy and Safety in Clinical Trials – Newly Diagnosed Patients) и DASISION (The Dasatinib versus Imatinib Study in Treatment-Naive CML Patients). Хотя прямое сравнение нилотиниба и дазатиниба в рамках разных исследований невозможно, но в статье приведены данные литературы по непрямому сравнительному статистическому анализу эффективности этих препаратов в сопоставимых группах пациентов. Полученные результаты дают основание предполагать, что применение новых ИТК в качестве 1-й линии, в особенности нилотиниба, позволит не только увеличить частоту ПЦГО, молекулярного ответа, беспрогрессивной выживаемости, но и вероятно повысит шанс пациентов на излечение.

Ключевые слова: хронический миелолейкоз, нилотиниб, дазатиниб.

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Target therapy with imatinib (IM) of chronic phase (CP) of chronic myeloid leukemia (CML) in the majority of patients leads to stable hematologic and cytogenetic remission. Nevertheless some patients don’t achieve complete cytogenetic remission (CCyR) or lose it afterwards. Besides after the achievement of major molecular response (MMR) risk of cytogenetic relapse and progression to accelerated phase (AP) or blast crisis (BC) tends to zero, but only a half of patients receive it on IM therapy. Achievement of complete molecular response (CMR) is more rare situation. Clinical trials of new tyrosine-kinase inhibitors (TKI) nilotinib and dasatinib as a frontline treatment in newly diagnosed CML CP patients proved their advantages above IM in achievement of CCyR and MMR. Nilotinib therapy also decreases risk of progression to AP/BP and increases overall survival. This review contains results of two multicentre international clinical trials ENESTnd (The Evaluating Nilotinib Efficacy and Safety in Clinical Trials – Newly Diagnosed Patients) and DASISION (The Dasatinib versus Imatinib Study in Treatment-Naive CML Patients). Although direct comparison of nilotinib and dasatinib in different trials is impossible, but this review contents description of indirect statistical analysis of nilotinib and dasatinib efficacy in comparable groups of patients. According to this results we can suppose that use of new TKIs as frontline treatment allows not only increase the probability of CCyR, MMR, overall survival, but also increase chances for cure in some patients.

Key words: chronic myeloid leukemia, nilotinib, dasatinib.

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Авторы

Н.С.Лазорко1, Е.Г.Ломаиа1, Е.И.Сбитякова1, А.Ю.Зарицкий2

1 ФГУ Федеральный центр сердца, крови и эндокринологии им. В.А.Алмазова Минздравсоцразвития РФ
2 ГОУ ВПО Санкт-Петербургский государственный медицинский университет им. И.П.Павлова

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N.S.Lazorko1, E.G.Lomaia1, E.I.Sbityakova1, A.Yu.Zaritskey2

1 Federal Heart Blood and Endocrinology Center named after V.A.Almazov
2 St.-Petersburg Pavlov's State Medical University

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