Background. Data from real-life clinical practice studies provide additional information on the efficacy of new antitumor therapy regimens, including in patients who meet exclusion criteria for clinical trials.Aim. To evaluate the Isaomex triplet efficacy in multiple myeloma patients in real clinical practice.Materials and methods. From 2021 to 2024, the retrospective study included 83 double refractory multiple myeloma patients from 26 centers aged 38 to 85 years (median 63), who received the Isaomex triplet. Glomerular filtration rate ˂ 60 mL/min was detected at the time of isatuximabbased triplet initiation in 18 % patients, 2 of whom were on program hemodialysis. The median of previous therapy lines was 2 (1–6). The median time from diagnosis to initiation of isatuximabbased triplet therapy was 47 months (5–203). Survival curves were constructed using the Kaplan–Meier method. Statistical analysis was performed using Statistica 10 program.Results. Isaomex triplet therapy resulted in overall and renal responses in 76 % and 61 % of cases, respectively. The median progression free survival was 13.5 months. In the group of patients who did not receive daratumumab at previous stages, the median progression free survival was significantly higher and was 28 months vs 8 months (p ˂ 0.05). Threeyear overall survival was 81 %. Discontinuation of isatuximab due to the development of adverse event was recorded in 2 cases (2 %). In the group of patients with bone plasmacytomas (n = 46), Isaomex therapy resulted in an overall response rate of 67 %; 12‑month progression free survival was 48 %, and 1‑year overall survival was 76 %.Conclusion. The results of the Isaomex triplet use in real clinical practice for the treatment of relapsed multiple myeloma showed data comparable to the ICARIA registration study on the frequency of achieving a response, duration of progression free survival and overall survival. The triplet efficiency was shown in comorbid patients, with advanced stages and those undergoing renal replacement therapy.

We retrospectively analyzed the effectiveness of ruxolitinib in patients with myelofibrosis (MF) in real clinical practice in Russia. The study included 42 patients with MF with an average age of 56 years from 10 inpatient and outpatient clinics. The majority of patients (55 %) belonged to the intermediate risk group 1 on the DIPSS scale, 86 % had massive splenomegaly and 88 % had constitutional symptoms. The average initial dose of ruxolitinib was 15 mg twice a day. At the time of analysis, 74 % of patients continued taking ruxolitinib with an average duration of therapy of 20 months. A decrease in the palpable size of the spleen by at least 50 % was recorded in 36 % and 46 % of patients assessed after 3 and 6 months of treatment, respectively. A correlation was found between OV, initial splenomegaly and splenic response after 3 months of therapy. It should be noted that no deaths were recorded in patients with a decrease in the size of the spleen by ≥ 50 %. There were no cases of discontinuation of treatment due to side effects. In general, in our retrospective study, ruxolitinib effectively controlled constitutional symptoms and reduced the size of the spleen in patients with MF. An early splenic response after 3 months of therapy is apparently a prognostic factor for OS, and a decrease in the size of the spleen by less than 25 % should be considered as treatment ineffectiveness in patients with MF taking ruxolitinib.

Aim. To assess the rate of DNMT3A, IDH1, IDH2, and ASXL1 gene mutations and their effect on the prognosis both as isolated findings and in combination with well-known chromosomal aberrations and gene mutations in newly diagnosed acute myeloid leukemia (AML) patients from some regions of the Russian Federation. Materials & Methods. The study enrolled 83 patients with newly diagnosed AML from 22 regions of the Russian Federation, who underwent molecular genetic examination for detecting IDH1 (R132), IDH2 (R140), ASXL1, and DNMT3A gene mutations with droplet digital PCR and Sanger sequencing methods. Results. The mutation rate in DNMT3A was 16.7 %, in IDH1 (R132) it was 6 %, in IDH2 (R140) it was 9.6 %, and in ASXL1 it was 6 %. The R140 mutation in IDH2 correlated with the older age of patients. The mutations in IDH1 (R132), IDH2 (R140), and DNMT3A showed a significant association with mutated NPM1. The mutations in IDH1 (R132), IDH2 (R140) were reported to occur significantly more often in patients with normal karyotype. The IDH1 (R132) and IDH2 (R140) mutations appeared to have a favorable effect on AML prognosis, which is most likely to be associated with a high rate of their compatibility with NPM1 mutation. The mutated type of DNMT3A had a negative effect on overall survival of patients with NPM1 mutation. The mutation in ASXL1 also appeared to be an unfavorable prognostic factor for overall survival of patients with wild type NPM1. Conclusion. A high rate of mutation occurrence in epigenetic regulation genes as well as the prognostic potential of these mutations in AML necessitate the need for determining the mutation status of DNMT3A, IDH1, IDH2, and ASXL1 in the context of primary diagnosis in real-world clinical practice.

Background. The national observational program MPN-QoL-2020 was focused on quality of life (QoL) and symptoms in patients with classical Ph-negative myeloproliferative neoplasms (MPNs) in the Russian Federation, as well as on the perception of the disease and treatment from the patient's and physician's perspective. Aim. To evaluate QoL in patients with different MPNs using new standardized questionnaires, to assess the most common symptoms and their impact on QoL in patients with myelofibrosis (MF), polycythemia vera (PV) and essential throm-bocythemia (ET), and to characterize the perception of the disease and treatment concerns from patients' perspective and their treating physicians' perspective. Materials & Methods. In total 1100 patients with MPNs (MF: n = 355, PV: n = 408, and ET: n = 337; mean age 58 ± 14 years; 61 % women) and 100 hematologists (mean age 42 ± 12 years; 85 % women) from 37 medical centers in 8 Federal districts of the Russian Federation participated in the study. All the patients filled out symptom assessment tool (MPN10), QoL questionnaire for patients with hematological nancies (HM-PRO) and patient's survey checklist; physicians filled out physician's survey checklist and patient record for each patient included in the study. Results. For the first time in Russia in a representative population of MPN patients in the real-world setting, QoL and symptom profiles in patients with different MPNs were characterized and symptom impact on the daily living of MPN patients was identified. MPN patients exhibited QoL impairment: noticeable detriments in physical and emotional functioning, as well as in eating and drinking regimen were found, social functioning was less impaired. More than one third of MPN patients had significant QoL impairment. The vast majority of patients experienced fatigue: 92.6 % MF patients, 83.7 % PI patients, and 82 % ET patients. Symptom prevalence severity differed across different MPNs. Top disease-related symptoms to be resolved were identified from patient's and physician's perspective. Discrepancies in the attitudes of MPN patients and their treating physicians to various aspects regarding the disease and its treatment were found as well as issues needed to be improved in the patient-physician communication were identified. Conclusion. The results of national research program MPN-QoL-2020 allowed to identify the areas of QoL impairment and symptom burden in MPN patients in Russia, to verify areas of concern related to the disease and its treatment in patients with different MPNs, as well as to highlight the unmet needs in this patients' population in our country. The outcomes of the study may contribute to establishing recommendations for improving/maintaining QoL in patients with MPNs and to developing measures aimed to raise awareness of this patients' population about the disease and its treatment.

Актуальность. Национальная наблюдательная программа МПН-КЖ-2020 была направлена на получение данных об особенностях качества жизни и симптомов, а также восприятия болезни и лечения при классических Ph-негативных миелопролиферативных новообразованиях (МПН) в Российской Федерации с точки зрения пациентов и врачей. Цель. При использовании новых стандартизованных опросников изучить качество жизни пациентов с различными МПН, дать характеристику наиболее распространенным симптомам и их влиянию на качество жизни больных миелофиброзом (МФ), истинной полицитемией (ИП) и эссенциальной тромбоцитемией (ЭТ), охарактеризовать восприятие проблем, связанных с заболеванием и лечением, с точки зрения самих пациентов и их лечащих врачей-гематологов. Материалы и методы. В исследование включено 1100 пациентов с Ph-негативными МПН (355 — с МФ, 408 — с ИП и 337 — с ЭТ; средний возраст пациентов 58 ± 14 лет, 61 % женщин). В исследовании также участвовали 100 врачей-гематологов (средний возраст 42 ± 12 лет, 85 % женщин) из 37 ЛПУ в 8 федеральных округах РФ. В рамках исследования пациенты однократно заполняли специальный опросник для оценки симптомов МПН (MPN10), специальный опросник качества жизни у онкогематологических больных (HM-PRO), а также опросный лист пациента. Гематологи однократно заполняли опросный лист врача, а также «карту пациента» на всех включенных ими в исследование больных МПН. Результаты. В условиях реальной клинической практики впервые в России получены данные об особенностях качества жизни пациентов с Ph-негативными МПН, профиле симптомов при разных вариантах МПН и степени их влияния на повседневную жизнь. Больные МПН имеют нарушения качества жизни, которые в большей степени касаются физического и эмоционального функционирования, а также режима приема пищи и питья, в меньшей — социального функционирования. Более чем у 1/3 больных с Ph-негативными МПН зарегистрировано значительное нарушение качества жизни. У подавляющего большинства пациентов отмечается слабость: при МФ — у 92,6 %, при ИП — у 83,7 %, при ЭТ — у 82 %. Профили актуальных симптомов и их выраженность отличаются при разных МПН. Определены симптомы, более всего требующие коррекции с точки зрения пациентов и врачей. Установлены расхождения в оценках пациентов и их лечащих врачей в отношении к заболеванию и проводимому лечению, а также аспекты, нуждающиеся в улучшении при взаимодействии пациент-врач. Заключение. Результаты, полученные в рамках национальной наблюдательной программы МПН-КЖ-2020, позволили выявить особенности нарушений качества жизни больных МПН в России. Определен спектр специфических проблем, связанных с заболеванием и лечением, которые характерны для этих пациентов. Кроме того, актуализированы неудовлетворенные потребности этой категории пациентов в нашей стране. Результаты программы МПН-КЖ-2020 могут использоваться при подготовке рекомендаций по улучшению/поддержанию качества жизни пациентов с Ph-негативными МПН и для разработки мероприятий, направленных на повышение осведомленности больных МПН о заболевании и его лечении.

Aim. To assess the efficacy of targeted therapy with ruxolitinib in patients with myelofibrosis in real clinical practice in Russia. To determine the prognostic value of spleen reduction in the early stages of ruxolitinib treatment and its effect on overall survival. Materials & Methods. The present retrospective study was based on the data of 10 centers of Russia. It included 56 myelofibrosis (primary or post-polycythemic and post-throm-bocythemic) patients who received ruxolitinib. The median age of patients was 56 years (range 26-76 years). Most of them (59 %) were considered intermediate-1 risk according Results. By the start of data collection most of patients (79 %) had been treated with ruxolitinib. In no case therapy was withdrawn for the reason of drug toxicity. On ruxolitinib constitutional symptoms were reversed in 70 %, 87 %, and 98 % of patients by months 1, 3 and 6, respectively. In 36 % and 46 % of patients by months 3 and 6, respectively, > 50 % decrease in spleen size was observed. Overall, in 31 % and 27 % of cases the size of the spleen decreased by less than 25 % by months 3 and 6, respectively. The factors affecting the changes in spleen size have not been identified. The probability of overall survival by years 2 and 5 of follow-up was 97 % and almost 70 %, respectively. This parameter was significantly affected by the extent of spleen size reduction by month 3 of follow-up as well as by its initial size. Conclusion. Ruxolitinib shows high efficacy for both decrease of general myelofibrosis symptoms and reduction in spleen size. The extent of spleen reduction is an important prognostic factor. It seems, that in patients with insufficient spleen reduction an increase in drug dose is advisable. If it is not possible, alternative methods of treatment should be sought.

The publication contains materials of the reports presented at the II Conference “Current Issues of Diagnosis and Treatment of Ph-Negative and Ph-Positive Myeloproliferative Neoplasms” held from 15 to 16 March 2019 at the National Research Center for Hematology (Moscow). The conference was organized to enable professional communication of the clinicians specializing in the treatment of myeloproliferative neoplasms (MPN), and the researchers in the related fields as well as to allow the exchange of views on the implementation of current diagnosis and treatment methods in Ph-negative and Ph-positive MPNs. Reports covered a wide range of rare and non-standard settings. Of particular importance was the opportunity to debate them in detail at panel discussions and interactive sessions. This format of the conference allowed to provide expert opinions in the present publication. It emphasizes the importance of complex diagnosis in MPN using morphological examination of bone marrow core biopsy samples and molecular genetic testing. Accordingly, the second day of the conference was devoted to a thorough analysis of the morphological characteristics of the cases presented and based on bone marrow core biopsy samples.

Цель. Оценить эффективность таргетной терапии руксолитинибом у пациентов с миелофиброзом в реальной клинической практике в России. Определить прогностическое значение динамики уменьшения размеров селезенки в ранние сроки лечения руксолитинибом и его влияние на общую выживаемость. Материалы и методы. Настоящий ретроспективный анализ проведен по данным 10 центров России. В исследование включено 56 пациентов с миелофиброзом (первичным или постполицитемическим и посттромбоцитемическим), получавших руксолитиниб. Медиана возраста пациентов составила 56 лет (диапазон 26–76 лет). Большинство из них (59 %) были с промежуточной-1 группой риска по шкале DIPSS, имели массивную спленомегалию (80 %) и конституциональные симптомы (86 %). Исходная доза препарата составляла 30 мг в сутки в 64 % случаев. При этом уровень тромбоцитов ≥ 200 × 109/л наблюдался у 61 % пациентов. Размеры селезенки оценивались пальпаторно. Результаты. К началу сбора данных большинство пациентов (79 %) продолжали лечение руксолитинибом. Ни в одном случае причиной прекращения терапии не была токсичность препарата. На фоне приема руксолитиниба конституциональные симптомы были купированы у 70, 87 и 98 % пациентов к 1, 3 и 6 мес. терапии соответственно. Уменьшение размеров селезенки на ≥ 50 % отмечено у 36 и 46 % пациентов к 3 и 6 мес. лечения соответственно. Всего в 31 и 27 % случаев размеры селезенки сократились на менее 25 % к 3 и 6 мес. терапии соответственно. Не удалось выявить факторы, влияющие на динамику изменения размеров селезенки. Вероятность общей выживаемости к 2 и 5 годам наблюдения составила 97 и почти 70 % соответственно. На этот показатель статистически значимо влияла степень уменьшения размеров селезенки к 3 мес. наблюдения, а также ее исходные размеры. Заключение. Руксолитиниб демонстрирует высокую эффективность в отношении как уменьшения общих симптомов миелофиброза, так и сокращения размеров селезенки. Степень редукции размеров селезенки является важным прогностическим фактором. У пациентов с недостаточным сокращением размеров селезенки целесообразно увеличение дозы препарата. При невозможности этого необходим поиск альтернативных методов лечения.

Ph-negative myeloproliferative neoplasm are the group of hematologic disorders which includes primary myelofibrosis, polycythemia vera, essential trombocytemia and several rare diseases. After the discovery of V617 Fgain-of-function mutation the new period of diagnostics, treatment and evaluating of MPN prognosis began. At the current moment several molecules inhibiting JAK2 function are developed. Advanced therapy in patients with primary and post-polycythemic myelofibrosis included molecules inhibiting JAK2 function resulted in rapid and durable improvements in splenomegaly and disease-related symptoms in the phase 3 trials COMFORT-I and COMFORT-II. The effectiveness of the advanced therapy included molecule inhibiting JAK2 was evaluated in three patients with primary myelofibrosis and post-polycitemic myelofibrosis. All represented clinical cases demonstrated positive dynamics of the disease manifested in spleen size reduction, improvement of the symptoms and in one case in reduction of blood transfusions. None of three patients met serious adverse events leading to dose reduction or discontinuation of the molecule inhibiting JAK2. Target agents therapy demonstrated high treatment rates in patients with primary and post-polycythemic myelofibrosis. Thus, it is clearly necessary to perform molecular diagnosis, screening tests at early stages of the chronic myeloproliferative disease for the selection of patients in need for specific treatment.

1 ФГБОУ ВО «Бурятский государственный университет» Медицинский институт, Улан-Удэ, e-mail: irinserg64@mail.ru; 2Республиканская клиническая больница им. Н.А. Семашко, Улан-Удэ Данная статья посвящена анализу заболеваемости множественной миеломой в Республике Бурятия. Множественная миелома, или миеломная болезнь (болезнь Рустицкого-Калера) злокачественное лимфопролиферативное заболевание, характеризующееся инфильтрацией костного мозга плазматическими клетками, наличием моноклональных иммуноглобулинов в сыворотке крови и в моче и поражением костей. В настоящее время в Бурятии, как и во всем мире, отмечается тенденция к росту заболеваемости миеломной болезнью. В работе дана характеристика структуры заболеваемости данной патологии и оценка результатов лечения пациентов, наблюдавшихся за период 2009-2015 гг. Установлено, что внедрение в клиническую практику новых схем терапии, а также аутологичная трансплантация костного мозга улучшает прогноз больных с множественной миеломой и позволяет добиться полноценной ремиссии у большинства больных. Проведенное исследование позволяет оценить эпидемиологическую ситуацию в республике и работу гематологической службы Республиканской клинической больницы им. Н.А. Семашко. Ключевые слова: эпидемиология, миеломная болезнь, моноклональные иммуноглобулины, костный мозг, аутологичная трансплантация.