Topic: 35. Quality of life and palliative care Background: Polycythemia vera (PV) is associated with troublesome symptoms and reduced quality of life (QoL). Although its treatment is risk-adapted and aims to minimize or improve symptoms, symptom burden is not included as a risk stratification factor for PV. Symptom burden and its impact on QoL may be underestimated in “low risk” patients (with age <60 and without prior thrombo-hemorrhagic events). Aims: The study, therefore, aimed to explore symptom burden and QoL in “low risk” PV patients and to compare such aspects with that in “high risk” PV. Methods: Patients with PV were selected from a cohort of participated in a cross-sectional nationwide survey MPN-QoL-2020 carried out in September-December 2020 in different areas of Russia. Patients aged ≥18 years with a confirmed diagnosis of PV and treated on the in-patient or outpatient basis were included in the analysis. For symptom and QoL assessment MPN10 and HM-PRO were used, respectively. The MPN10 assesses 10 of the most clinically relevant symptoms, including fatigue and generates a Total Symptom Score (TSS). The HM-PRO is a specific QoL questionnaire for patients with hematologic malignancies developed for the use in clinical practice. It consists of two scales: Part A measuring the ‘impact on patients’ QoL’; Part B – ‘signs and symptoms’ (S&S) experienced by the patients. Part A has 4 domains: physical behavior (PB), social well-being (SW), emotional behavior (EB), eating and drinking habits (ED). Higher scores indicate greater impact. Exploratory analyses were carried out applying descriptive statistics, χ2 test and Mann-Whitney U test. Results: Altogether 265 PV patients were included in the analysis: 95 patients were identified as “low risk” (mean age±SD – 48.8±11.6 yrs; 49.5% males) and 170 patients as “high risk” PV (mean age – 62.9±12.3 yrs; 45.3% males). In the “low risk” group, 69.5% received cytoreductive treatments (CT) – hydrea (64%), interferons (30%), ruxolitinib (6%); in the high risk group, 86.5% received CT – hydrea (79%), interferons (15%), ruxolitinib (6%). Among “low risk” PV, 94.7% reported at least 1 PV-related symptom. The most frequently reported symptoms of MPN10 were inactivity (83%), fatigue (81%) and itching (65%). Symptoms with the highest reported mean severity scores were fatigue (3.3±2.6), inactivity (3.3±2.6), problems concentrating (2.8±2.9) and itching (2.6±2.9). More than half of “low risk” patients (61.5%) experienced moderate-to-severe symptoms (4-10 scores). Symptom burden according to MPN10 TSS was similar to “high risk” patients: 20.4±16.5 vs 24.6±18.4 (ns). Prevalence of moderate-to-severe symptoms did not differ significantly between “low risk” (61.5%) and “high risk” (71.7%) PV (ns). In “low risk” PV, the highest impact on QoL by HM-PRO (Part A) was for EB (Table). According to HM-PRO Part A and S&S, 26.3% and 44.2% patients exhibited moderate/very large/extremely large effect on QoL and S&S, respectively (Table). In “high risk” PV these proportions were 38.2% and 52.3%, respectively (ns). QoL impact and S&S were higher in “high risk” than in “low risk” PV (p<0.05), Table. Summary/Conclusion: In conclusion, the vast majority of patients with “low risk” PV reported high PV-related symptoms/ symptom burden and impact on QoL. Further prospective studies are worthwhile to explore the determinants of symptom burden in “low risk” PV. Furthermore, the results suggest that risk profiling may not capture all aspects of disease burden in PV and this highlights the importance of using patient-reported outcomes, namely MPN10 and HM-PRO, to identify unmet patients’ needs, especially in “low risk” PV.Keywords: Risk factor, Quality of life, Polycythemia vera

Aim. To study the quality of life in patients with chronic immune thrombocytopenia (ITP) in the process of romiplostim therapy and to assess the efficacy and safety of this drug in real-world setting. Materials & Methods. The study enrolled adult patients with the confirmed chronic ITP diagnosis and indications for romiplostim therapy. Clinical parameters, RAND SF-36 and FACT-Th6 quality of life as well as FACIT-Fatigue scores were evaluated prior to romiplostim administration vs. 3, 6, and 12 months after the treatment onset. Patient satisfaction checklist was also administered at all study points after the start of therapy. The clinical efficacy of romiplostim was analyzed along with assessing response and time to response. To study the quality of life and fatigue changes, the Generalized Estimating Equation (GEE) method was used during the observation period. Significant fatigue changes were determined and compared in terms of the perception differences from patient’s and physician’s perspective. Results. The study enrolled 60 chronic ITP patients treated with romiplostim in the real-world setting (mean age 51.9 years, 70 % women). The median thrombocyte count prior to romiplostim therapy was 18.5 × 109/L (interquartile range 10.8–22.3 × 109/л). On the enrollment date, 90 % of patients showed hemorrhagic syndrome. Overall response to romiplostim therapy was 98.3 % (complete response was achieved in 93.3 % of patients). After 6 months of therapy, 89.5 % of patients preserved response. After 3 months of therapy, hemorrhagic syndrome was eliminated in 81 % of patients, after 6 months the same was achieved in 93 % of patients. The median time to response was 4.4 weeks (95% confidence interval 3.6–5.3 weeks). Adverse events of grades 1/2 associated with romiplostim were reported in 6.7 % of patients. On romiplostim therapy, pronounced positive changes in quality of life were shown by all scales of the general questionnaire SF-36 and the targeted questionnaire FACT-Th6 (p < 0.001). The clearest improvements were observed in role-physical and role-emotional functioning. Already after 3 months of therapy, a considerable fatigue reduction was observed and sustained for the next 6 and 12 months of romiplostim administration (p < 0.001). During the therapy, the proportion of patients with fatigue impacting various aspects of functioning became considerably smaller. The vast majority of patients (85 %) were satisfied with the treatment. Discrepancies between patients’ and physicians’ evaluations of fatigue were also identified during the treatment. Conclusion. The results of the present multi-center observational study demonstrate high efficacy and safety of romiplostim for chronic ITP patients in the real-world setting. Romiplostim therapy yields considerable quality of life improvement and fatigue reduction. To optimize the patient monitoring system and patient-centered ITP treatment in the real-world setting, it is advisable to use the standardized questionnaires assessing quality of life and fatigue.

Aim. To study the quality of life and symptoms, to assess the clinical effect and treatment safety in relapsed/refractory classical Hodgkin’s lymphoma (r/r cHL) patients treated with brentuximab vedotin (BV) as > 3rd-line therapy in the context of real clinical practice. Materials & Methods. The study enrolled 62 r/r cHL patients after the second- and subsequent-line chemotherapies, who are either ineligible for autologous hematopoietic stem cell transplantation (auto-HSCT) at the time of their enrollment into the study or after the failure of high-dose chemotherapy (HDCT) with auto-HSCT. The median age was 31 years; 46.8 % of patients were women. The patients received BV 1.8 mg/kg intravenously every 3 weeks. Clinical parameters, quality of life, and symptoms were assessed prior to BV therapy and in 3, 6, 9, 12, and 15 months after therapy onset. The RAND SF-36 form was used to assess the quality of life, and the ESAS-R tool was applied to report on symptoms. Results. Objective response was observed in 68.3 % of patients, 40 % out of them showed complete response. The median progression-free survival was 10.6 months (95% confidence interval 7.4-12.9 months). Safety profile corresponded to the published data. Adverse events of grade 3/4 were identified in 1.6 % of patients. In the period of 15 months after therapy onset, quality of life improvement or stabilization was reported based on all the scales of RAND SF-36 (GEE, p < 0.001), and symptom relief was shown based on ESAS-R total score (GEE, p < 0.001). Conclusion. In the context of real clinical practice, BV appeared to be effective in r/r cHL patients either after the second- or subsequent-line chemotherapies or after the failure of HDCT with auto-HSCT. The study demonstrated that BV was well tolerated by the patients. BV therapy contributes to the improvement of r/r cHL patients’ quality of life. Positive changes in quality of life and symptoms on BV therapy testify to its patient-assessed efficacy and safety.

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.

There are only limited data coming from isolated case reports regarding the real-world use of emicizumab for the treatment of children with hemophilia A and inhibitors (HAI) in Russia. The aim of the study was to evaluate the efficacy and safety of emicizumab prophylaxis in children with severe HAI. Ethical approval was not required since the study only involved the use of anonymized and generalized retrospective data obtained during routine clinical practice. We retrospectively analyzed medical records of children with HAI who had been treated with emicizumab at 11 institutions located in Russia, taking into consideration such parameters as annualized bleeding rates (ABR), annualized spontaneous bleeding rates (ASBR), annualized joint bleeding rates (AJBR) and annualized bleeding rates for bleeds requiring additional therapy (ABRRT), as well as the presence and severity of adverse events during the treatment. The median age of patients at the time of initiation of emicizumab prophylaxis was 65 (11–170) months. Before the treatment, ABR was 19.9 (95% confidence interval (CI), 15.4–26.1), ASBR – 13.6 (95% CI, 10.6–17.8), AJBR – 6.6 (95% CI, 4.7–9.7), ABRRT – 16.6 (95% CI, 12.4–22.7). After the initiation of the treatment, bleeding rates changed dramatically: ABR decreased by 98.6% (95% CI, 96.7–99.4), AJBR – by 99.4% (95% CI, 95.3–99.9), ABRRT – by 98.8% (95% CI, 96.8–99.6); and there were no signs of spontaneous bleeding during 10 (1–32) months of treatment. No adverse events leading to the interruption or discontinuation of the treatment with emicizumab were reported. The use of emicizumab in children with HAI in the real-world clinical setting results in a significant (> 98%) and safe reduction in bleeding episodes without any signs of spontaneous bleeding.

Цель. Изучение качества жизни и симптомов, оценка клинического эффекта и безопасности лечения у пациентов с рецидивами и рефрактерным течением классической лимфомы Ходжкина (р/р кЛХ), получающих брентуксимаб ведотин (БВ) в качестве ≥ 3-й линии терапии в условиях реальной клинической практики. Материалы и методы. В анализ включено 62 больных р/р кЛХ после второй или последующих линий противоопухолевой терапии, не являющихся кандидатами для проведения трансплантации аутологичных гемопоэтических стволовых клеток (аутоТГСК) на момент включения в исследование, или после неудачи высокодозной химиотерапии (ВДХТ) с аутоТГСК. Медиана возраста — 31 год, 46,8 % — женщины. Пациенты получали БВ в дозе 1,8 мг/кг в/в каждые 3 нед. Оценку клинических показателей, качества жизни и симптомов проводили до начала терапии БВ и через 3, 6, 9, 12 и 15 мес. после начала лечения. Для оценки качества жизни применяли опросник RAND SF-36, для оценки симптомов — ESAS-R. Результаты. Объективный ответ зарегистрирован у 68,3 % больных, из них 40 % имели полный ответ. Медиана выживаемости без прогрессирования составила 10,6 мес. (95%-й доверительный интервал 7,4–12,9 мес.). Профиль безопасности соответствовал опубликованным данным. Нежелательные явления III–IV степени тяжести выявлены у 1,6 % больных. На протяжении 15 мес. после начала лечения отмечались улучшение или стабилизация качества жизни по всем шкалам опросника RAND SF-36 (GEE, p < 0,001), а также уменьшение выраженности симптомов по общему баллу опросника ESAS-R (GEE, p < 0,001). Заключение. В условиях реальной клинической практики подтверждена эффективность применения БВ у больных р/р кЛХ после второй или последующих линий противоопухолевой терапии либо после неудачи ВДХТ с аутоТГСК. Продемонстрирован удовлетворительный профиль переносимости БВ. Терапия БВ сопровождается улучшением качества жизни больных р/р кЛХ. Положительные изменения качества жизни и симптомов на фоне терапии БВ свидетельствуют о его эффективности с точки зрения пациента.

Aim. To assess the efficacy and safety of using the drug Extimia BIOCAD (international nonproprietary name INN: empegfilgrastim) in order to reduce the frequency and duration of neutropenia, the frequency of febrile neutropenia (FN) and infections manifested by FN in patients with lymphoproliferative diseases receiving myelosuppressive therapy. Materials and methods. This publication presents the interim results of a multicenter retrospective prospective observational post-marketing study of the safety and efficacy of the drug Extimia BIOCAD (INN: empegfilgrastim) in patients with lymphoproliferative diseases receiving cytotoxic therapy (LEGERITY). The interim data analysis included 40 patients with lymphoproliferative diseases (Hodgkins lymphoma, diffuse large B-cell lymphoma, multiple myeloma, primary mediastinal large B-cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia, splenic marginal zone lymphoma), who were treated in ten research centers of the Russian Federation (Moscow, St. Petersburg, regional clinics). The median age of patients was 48 (2172) years, 13/40 (32.5%) patients belonged to the older age group (60 years). Patients had functional status on the ECOG scale of 02 and received at least 2 chemotherapy injections against the background of prophylaxis with empegfilgrastim. Empegfilgrastim was administered at a dose of 7.5 mg subcutaneously once 24 hours after the end of the administration of cytotoxic chemotherapeutic agents. Primary endpoint: frequency of neutropenia 35 degrees of severity; secondary endpoints: frequency of FN; frequency of severe infections (34 stages); frequency of antibiotic prescription; relative dose intensity of therapy of the conducted chemotherapy courses; the incidence of all adverse reactions in patients who received at least one dose of the study drug empegfilgrastim; the incidence of all serious adverse reactions in patients who received at least one dose of the study drug empegfilgrastim; the incidence of CTCAE 5.0 grade 34 HP in patients who received at least one dose of the study drug empegfilgrastim; discontinuation rate of study drug empegfilgrastim due to adverse reactions. Results. The results of this study demonstrate that the incidence of neutropenia of 3 degree of severity after the 1st cycle of chemotherapy developed in 2/40 patients (5%) and as a result of high-dose therapy (R-DHAP). Neutropenia of any severity was reported in 5/40 patients (12.5%). Cases of FN development have not been registered. Severe infections (mucositis, enteropathy, pneumonia, etc.), as well as the use of antibacterial and antifungal drugs during 1 cycle of chemotherapy and in the inter-course period after 1 cycle of therapy were not recorded in any patient. The next course of myelosuppressive therapy was not delayed due to the development of neutropenia in any of the patients during the study. Adverse events, according to the researcher, associated with the use of empegfilgrastim, were registered in 2/40 patients (5%): moderate generalized pain syndrome (diffuse pain) of 1 severity and in one case ossalgia of 2 severity. No serious adverse reactions were reported. Conclusion. The results of the interim analysis of the study demonstrate the high efficacy of the first Russian original pegylated granulocyte colony-stimulating factor empegfilgrastim after a single administration of a fixed dose in the treatment of patients with aggressive and indolent lymphomas. The drug has a favorable tolerance profile in any age group of patients, especially in elderly patients. Administration of empegfilgrastim as a prophylaxis of neutropenia in patients with lymphoproliferative diseases receiving myelosuppressive therapy of varying intensity can reduce the burden on medical personnel, improve patient adherence to treatment, and contribute to the implementation of the therapeutic plan.