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: Comprehensive evaluation of new treatment regimens in RRMM patients both from physician's and patients' perspective is worthwhile. Aims: We aimed to evaluate clinical and patient-reported outcomes during IRd treatment as ≥ 2nd line in RRMM patients in a multicenter real-world evidence study. Methods: Adult patients with RRMM who have been assigned IRd as ≥2nd line treatment were enrolled in 18 centers of Russian Federation from April 2019 till May 2020. Treatment response was evaluated by IMWG 2011 criteria. For assessment of adverse events (AEs) NCI CTCAE v. 4.0 was used. Patients filled out RAND SF-36 and ESAS-R questionnaires at baseline, at 1 and 3 mos, and thereafter every 3 mos till 18 mos after IRd treatment onset. Statistical analysis of patient-reported outcomes was conducted using GEE with adjustment to age, gender and baseline quality of life (QoL). Duration of response (DOR), progression-free (PFS) and overall survival (OS) from the start of IRd treatment were evaluated using Kaplan-Meyer method. Results: In total, 40 patients with RRMM were enrolled into the study: median age – 64 years (range, 33–80), 35% males. Durie–Salmon stage at study entry: II/III – 40/60%, ECOG status 0/1 – 70%, 2/3 – 30%. Median time since initial MM diagnosis – 55 mos (range, 2.0–99.0). Median number of lines of prior therapy – 3 (range, 1–7). Comorbidities were revealed in 65% patients; median Charlson Comorbidity index – 2 (range, 0–5); 95% patients had bone complications. The median duration of IRd treatment – 7.5 mos (IQR, 3.9-18.0). Two-thirds of the patients (28/39) responded to therapy. The overall response rate was 46.2% (95%CI: 30.6-61.8), median DOR – 16.3 mos (95%CI: 15.4–17.3). Among them 3 patients achieved complete response, 1 – stringent complete response, 2 – very good partial response, 12 – partial response. Ten patients had minor response. Clinical benefit rate – 71.8% (95%CI: 57.7-85.9). Six patients (15.4%) had stable disease and 4 (10.3%) progressed upon therapy. Median PFS was 10.6 mos (95%CI: 6.3-16.3). During the entire period of the study 5 deaths were registered: 3 were related to progression, 2 – because of COVID-19. Мedian OS was not reached. One-year OS rate was 85.2% (95%CI: 71.0–99.0). AEs were revealed in 55% patients: grades 1-2 AEs – 15 patients; grades 3-4 AEs – 7 patients; SAEs – 3 patients (neurological toxicity, gastric bleeding, hypotension and diarrhea). Baseline QoL was dramatically impaired by the majority of SF-36 scales; 42% patients experienced severe/critical QoL impairment. At baseline all the patients experienced symptoms; 85% with moderate-to severe symptoms (≥4 scores on the scale from 0 to 10). The most prevalent and severe symptoms were tiredness (98%), drowsiness (90%), pain (82%) and shortness of breath (80%). During IRd treatment QoL was stable or improved. Physical and role physical functioning, general health, vitality and mental health significantly improved as compared to baseline (GEE, p<0.05). Twice increase of Integral QoL Index was observed – 0.27 at baseline vs 0.48 at 18 mos (p<0.05). Severity of pain, tiredness and nausea meaningfully decreased during IRd treatment as compared to baseline (GEE, p<0.05). Total ESAS-R score decreased by 10 points at 18 mos of therapy as compared to baseline – 31 vs 21 (GEE, p<0.05). Summary/Conclusion: In summary, results obtained in a real-world evidence study confirmed RCTs data that IRd regimen is an effective treatment in RRMM patients. This treatment is accompanied with definite improvement of QoL. Our results demonstrate benefits of IRd, both from physician's and patient's perspective.

Background: Short-pulse NHL-BFM-90 chemotherapy is highly effective in pediatric aggressive B-cell lymphomas. We modified R3 arm of NHL-BFM-90 program (named R-mNHL-BFM-90) for adults under 60 years with high-risk de novo DLBCL and conducted the randomized study compared to well-known R-DA-EPOCH-21 chemotherapy Aims: to evaluate R-mNHL-BFM-90 and R-DA-EPOCH-21 efficacy and toxicity and auto-HSCT reasonability as well in de novo adult DLBCL patients with 2 or more signs of poor prognosis Methods: Treatment protocol was registered as NCT02842931 at www.clinicaltrials.gov. Inclusion criteria were newly diagnosed DLBCL, not otherwise specified (NOS), according WHO, 2008 and 2017 criteria; two or more signs of poor prognosis (i.e. intermediate and high aaIPI risk); age 18-60. Complete remission (CR), partial remission (PR) or disease progression (DP) corresponded Lugano 2014 criteria. The study design intended randomization for four parallel arms. The first one was 6-cycle R-DA-EPOCH-21 as described earlier. The second, 6-cycle R-DA-EPOCH-21 plus auto-HSCT. The third, 6-cycle (A-B-A-B-A-B) R-mNHL-BFM-90. In addition, the fourth one was 6-cycle R-mNHL-BFM-90 plus auto-HSCT. If CR was not achieved after 6-cycle initiating treatment in every arm additionally 2-cycle R-DHAP chemotherapy were completed before auto-HSCT if intended. G-CSF after chemotherapy was administrated according clinical guides. A total of 140 patients from 13 medical Russia clinics were included from February 2015 to June 2021. Randomization was done according “intention-to-treat” as follows: R-DA-EPOCH-21 (35 patients); R-DA-EPOCH-21+auto-HSCT (30 patients); R-mNHL-BFM-90 (37 patients); R-mNHL-BFM-90+auto-HSCT (38 patients). Ten patients were excluded from the cohort due various reasons. Therefore, the first-step analysis was carried out for 130 patients according “intention-to-treat”. In cases of PR after 6 cycles or progression at any treatment stage or relapse (a total 14 patients) we performed the second tumor biopsy. In all cases, the final diagnosis was assessed as indolent lymphoma transformation into DLBCL or other “non-DLBCL” lymphomas. So, the second-step analysis was performed for 116 “proved” de novo DLBCL patients. Results: Evaluation of comparative efficacy was carried out in R-DA-EPOCH-21±auto-HSCT and R-mNHL-BFM-90±auto-HSCT cohorts. Detailed results are presented in Table 1. Hematological/non-hematological toxicity was acceptable in all groups. However, neutropenic fever and grade 3-4 thrombocytopenia differed statistically significantly (χ2 test, p<0.05) between R-DA-EPOCH-21 and R-mNHL-BFM-90 arms. The value of auto- auto-HSCT will be determined later. Image:Summary/Conclusion: Thus, de novo DLBCL NOS is potentially curable disease with no relapses. R-mNHL-BFM-90 program is highly effective in de novo DLBCL NOS adult patients. R-mNHL-BFM-90 therapy toxicity is acceptable. The estimated CR duration probability within 10 months after treatment completion in the high-risk group is 100% in R-mNHL-BFM-90 group compared to 57% in R-DA-EPOCH group (χ2 test, p=0.0047).

Aim. To study quality of life (QoL) indicators and symptom profile as well as treatment satisfaction of patients with relapsed/refractory multiple myeloma (r/r MM) on triplet therapy based on ixazomib combined with lenalidomide and dexamethasone (IxaRd); to assess efficacy and safety of IxaRd protocol in real-world clinical practice. Materials & Methods. The study enrolled 40 patients with confirmed r/r MM diagnosis, aged > 18 years, at 18 Russian health care institutions. They received at least one line of prior therapy and were IxaRd-eligible. Clinical and QoL indicators were assessed according to the RAND SF-36, and symptoms were evaluated using the ESAS-R questionnaire prior to IxaRd therapy and in 1, 3, 6, 9, 12, 15, and 18 months after its start. Besides, patients filled out checklists for assessment of treatment satisfaction at all time-points after therapy onset. The analysis of clinical IxaRd efficacy included assessment of treatment response by IMWG 2011 criteria, as well as response duration, overall survival (OS), and progression-free survival (PFS). The analysis of IxaRd safety was based on reporting adverse events (AEs), including severe ones (SAEs). To analyze patient-reported QoL and symptom changes during follow-up, GEE was used. To determine clinically meaningful changes, an effect size was calculated. Results. The study included 40 r/r MM patients (mean age 63 ± 9 years, 65 % women). Median disease duration before IxaRd therapy onset was 55 months (range 2-99 months). 60 % of patients had IIIA/IIIB Durie-Salmon stage. With the median IxaRd duration of 7.5 months, clinical benefit rate was 71.8 %. Complete response was reported in 7.7 % of patients, stringent complete response in 2.6 % of patients, very good partial response in 5.1 % of patients, partial response in 30.8 % of patients, and minor response was achieved in 25.6 % of patients. Stable disease was reported in 15.4 % of patients, and disease progression was identified in 10.3 % patients, including immunochemical relapse in 1 patient. The median response duration was 16.3 months (95% confidence interval [95% CI] 15.4-17.3 months), the median PFS was 10.6 months (95% CI 6.3-16.3 months). The median OS was not reached; the 1-year OS after IxaRd therapy onset was 85.2 % (95% CI 71-99 %). AEs on IxaRd therapy were reported in 55 % of patients, SAEs were reported in 3 (7.5 %) patients. Positive QoL changes were observed on IxaRd therapy. QoL improvement was meaningful in terms of physical functioning, role-physical functioning, general health, vitality, and mental health, compared to baseline. Moreover, a considerable decrease of pain, fatigue, and nausea was revealed. On the whole, 87.5 % of patients were satisfied with the triplet IxaRd therapy. Conclusion. The results of the present pilot study demonstrate efficacy and safety of the triplet IxaRd therapy (all per os) in real-world clinical practice from r/r MM patients’ and physicians’ perspective. Our data testify to the importance of patients’ feedback in the evaluation of therapy efficacy.

Цель. Изучить показатели качества жизни (КЖ) и спектр симптомов, а также удовлетворенность лечением у пациентов с рецидивами/рефрактерной множественной миеломой (р/р ММ) на фоне трехкомпонентного режима терапии иксазомибом в комбинации с леналидомидом и дексаметазоном (IxaRd). Оценить эффективность и безопасность терапии по схеме IxaRd в условиях реальной клинической практики. Материалы и методы. В исследование включено 40 пациентов старше 18 лет из 18 ЛПУ РФ с подтвержденным диагнозом р/р ММ, которые получили как минимум одну линию предшествующей терапии и которым показано лечение по схеме IxaRd. Оценку клинических показателей, КЖ по опроснику RAND SF-36 и симптомов по опроснику ESAS-R проводили до начала терапии IxaRd и через 1, 3, 6, 9, 12, 15 и 18 мес. после ее начала. Кроме того, заполнялась анкета удовлетворенности пациента лечением во всех точках исследования после начала терапии. Анализ клинической эффективности IxaRd включал оценку ответа на лечение согласно IMWG-2011, а также длительности ответа, общей выживаемости (ОВ) и выживаемости без прогрессирования (ВБП). Анализ безопасности режима IxaRd включал регистрацию нежелательных явлений (НЯ), в т. ч. серьезных (СНЯ). Для анализа изменений КЖ и симптомов в процессе наблюдения применяли метод обобщенных уравнений оценки (GEE). Для определения клинически значимых изменений рассчитывали величину эффекта (ES). Результаты. В исследование включено 40 пациентов с р/р ММ (средний возраст 63 ± 9 года, 65 % женщин). Медиана длительности заболевания до начала терапии IxaRd составила 55 мес. (диапазон 2–99 мес.). У 60 % больных была IIIA–IIIB стадия р/р ММ по Durie—Salmon. При медиане длительности терапии IxaRd 7,5 мес. ответ на лечение получен у 71,8 % пациентов. Полный ответ составил 7,7 %, строгий полный ответ — 2,6 %, очень хороший частичный ответ — 5,1 %, частичный ответ — 30,8 %, малый ответ — 25,6 %. Стабилизация заболевания зарегистрирована у 15,4 % больных, прогрессирование болезни — у 10,3 %, включая иммунохимический рецидив у 1 пациента. Медиана длительности ответа составила 16,3 мес. (95%-й доверительный интервал [95% ДИ] 15,4–17,3 мес.), медиана ВБП — 10,6 мес. (95% ДИ 6,3–16,3 мес.). Медиана ОВ не достигнута; 1-летняя ОВ при расчете длительности жизни от начала терапии IxaRd составила 85,2 % (95% ДИ 71–99 %). НЯ на фоне терапии IxaRd зарегистрированы у 55 % пациентов, СНЯ — у 3 (7,5 %). Констатирована положительная динамика КЖ в процессе терапии IxaRd. Улучшение КЖ было значимым по шкалам физического функционирования, ролевого физического функционирования, общего здоровья, жизнеспособности и психического здоровья по сравнению с исходными показателями. Кроме того, выявлено существенное уменьшение выраженности боли, усталости и тошноты. В целом 87,5 % пациентов удовлетворены трехкомпонентным режимом терапии IxaRd. Заключение. Результаты настоящего пилотного исследования позволили продемонстрировать эффективность и безопасность трехкомпонентного режима терапии IxaRd (все препараты для приема внутрь) в реальной клинической практике при р/р ММ с точки зрения пациентов и врачей. Наши данные свидетельствуют о важности учета мнения пациента при оценке эффективности проводимого лечения.

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.

Background: NHL-BFM-90 chemotherapy is highly effective in pediatric aggressive B-cell lymphomas. Purpose: To evaluate the efficacy and toxicity of the R-mNHL-BFM-90 and R-DAEPOCH-21 programs in adult patients with de novo DLBCL. Patients and methods: Inclusion criteria: newly diagnosed DLBCL (NOS), no previous chemotherapy, 2 or more signs of poor prognosis, age 18-60. The protocol included 140 patients from 13 medical centers in Russia: R-DA-EPOCH-21 – 33; R-DAEPOCH-21+auto-HSCT - 29; R-mNHL-BFM-90 - 33; R-mNHL-BFM-90+ auto-HSCT -35 patients. R-DA-EPOCH-21 branch: 6 courses were performed. If CR was not achieved, 2 courses of R-DHAP were performed ± auto-HSCT. Branch R-mNHL-BFM-90 included 6 cycles: RA-RB-RA-RB-RA-RB. If CR was not achieved, 2 courses of R-DHAP ± auto-HSCTResults: Of 62 patients on R-DA-EPOCH-21±auto-HSCT, CR was achieved in 36 (58.1%) patients, PR was achieved in 14 (22.6%) patients, progression was reported in 6 (9.7%) patients, 3 (4.8%) patients had died, and treatment continued in 3 (4.8%) patients. Of 68 patients on R-mNHL-BFM-90±autoHSCT CR was achieved in 63 (92.7%) patients, PR was achieved in 2 (2.9%) patients, progression was not reported, 2 (2.9%) patients had died, and treatment continued in 1 (1.5%) patient. The 4-year OS of patients in the high-risk group 94% on R-mNHL-BFM-90 therapy, 81% on R-DA-EPOCH-21 therapy;. the 4-year EFS of patients in the high-risk group was 78% and 43%, respectively (p = 0.0004). Conclusion: R-mNHL-BFM-90 program is highly effective in de novo DLBCL NOS adult patients; toxicity is acceptable.

Цель. Наблюдательная программа была направлена на получение данных об особенностях распространения классической лимфомы Ходжкина (кЛХ) в Российской Федерации, вариантах терапии и клинических исходах лечения. Цель проспективной части программы заключалась в стандартизации подходов к лечению и сравнении его результатов с терапией вне рамок протокола. Материалы и методы. В проспективно-ретроспективной наблюдательной программе по лечению лимфомы Ходжкина участвовало 32 региональных и федеральных центра. Включено 218 пациентов, из них 21 в проспективную часть программы RNWOHG-HD1 (Russian North-West Oncology and Hematology Group — Hodgkin Disease Study 1). Медиана возраста составила 36 лет (диапазон 22–87 лет). I и II стадии кЛХ определены у 48 % пациентов, III–IV — у 52 %. В проспективной части программы использовался эскалационный протокол при I–IIA стадии и отсутствии факторов риска, деэскалационный протокол — у пациентов с распространенными стадиями. В анализ общей (ОВ) и выживаемости без прогрессирования (ВБП) включено 160 и 152 пациента соответственно. ПЭТ-КТ использовалась для оценки ответа у 33 % пациентов. Результаты. В исследовании применялись следующие схемы химиотерапии первой линии: ABVD в 42 % случаев, BEACOPPst — в 11 %, BEACOPP-14 — в 17 %, BEACOPPesc — в 25 %, EACOPP — в 1 %. После завершения первой линии терапии частота объективного ответа составила 91 %, в т. ч. 61 % полных ответов. Структура ответа статистически значимо не различалась в группах неинтенсивной химиотерапии (ABVD и BEACOPPst), интенсифицированных режимов (BEACOPP-14, BEACOPPesc, EACOPP) и лечения по протоколу RNWOHG-HD1 (91, 92 и 96 % соответственно; p = 0,7226). В общей группе пациентов 3-летняя ОВ составила 97 % (95%-й доверительный интервал [95% ДИ] 94–99 %), ВБП — 87 % (95% ДИ 80–92 %). 3-летняя ВБП не различалась в группах пациентов, получавших ABVD, BEACOPPst, BEACOPP-14, BEACOPPesc и терапию по протоколу RNWOHG-HD1 (p = 0,37). Международный прогностический индекс (IPS) позволил получить статистически значимые результаты прогноза ВБП за счет пациентов с оценкой 5–6 баллов, но не 1–4 балла (p = 0,0028). Заключение. Наблюдательная программа продемонстрировала, что большинство участвовавших центров использует риск-адаптированный подход ABVD/BEACOPPesc, что определяет отсутствие различий в ВБП при этих вариантах химиотерапии. Исследование выявило необходимость использования ПЭТ-КТ для оценки ответа, т. к. одна КТ не позволяет дифференцировать полный и частичный ответы у значительного числа пациентов. В РФ вполне может быть реализована проспективная унифицированная программа лечения кЛХ.

Aim. The observational program was aimed at obtaining data on classical Hodgkin's lymphoma (cHL) incidence in the Russian Federation, therapy options, and clinical outcomes of treatment. The aim of the prospective part of the program was to standardize the approaches to therapy and to compare its outcomes with off-protocol treatment. Materials & Methods. The prospective-retrospective observational program for Hodgkin's lymphoma treatment engaged 32 regional and federal centers. It included 218 patients, 21 out of them were included into the prospective part of the RNWOHG-HD1 (Russian North-West Oncology and Hematology Group - Hodgkin Disease Study 1) program. The median age was 36 years (range 22-87 years). cHL stages I/II were identified in 48 % of patients, III/IV stages were reported in 52 % of patients. The prospective part of the program used escalating protocol in patients with stages I/IIA and without risk factors and de-escalating protocol in patients with advanced stages. Overall (OS) and progression-free (PFS) survivals were analyzed in 160 and 152 patients, respectively. PET-CT was used to assess the response in 33 % of patients. Results. The study used the following first-line chemotherapy regimens: ABVD in 42 %, BEACOPPst in 11 %, BEACOPP-14 in 17 %, BEACOPPesc in 25 %, and EACOPP in 1 % of cases. After the completion of first-line therapy objective response rate was 91 % including 61 % of complete responses. Response structure did not significantly differ in the groups of non-intensive therapy (ABVD and BEACOPPst), intensified regimens (BEACOPP-14, BEACOPPesc, and EACOPP), and treatment according to the RNWOHG-HD1 protocol (91 %, 92 %, and 96 %, respectively; p = 0.7226). In the total cohort the 3-year OS was 97 % (95% confidence interval [95% CI] 94-99 %), PFS was 87 % (95% CI 80-92 %). The 3-year PFS did not differ in ABVD, BEACOPPst, BEACOPP-14, BEACOP-Pesc, and RNWOHG-HD1 recipients (р = 0.37). International Prognostic Score (IPS) yielded significant results in PFS prediction for patients with IPS score of 5-6, but not for those with IPS score of 1-4 (p = 0.0028). Conclusion. The observational program showed that the majority of participating centers use the risk-adapted ABVD/ BEACOPPesc approach which explains no difference in PFS being found with the use of these chemotherapy options. The study demonstrated the need for PET-CT to assess the response since the CT alone cannot distinguish between complete and partial responses in a considerable number of patients. The prospective unified program for cHL treatment may well be implemented in the Russian Federation.

The goal of treatment of relapsed/refractory multiple myeloma (RRMM) is to control the disease, prolong survival, reduce disease-related symptoms, and improve quality of life (QoL). Comprehensive evaluation of new treatment regimens in RRMM pts is worthwhile. We aimed to evaluate QoL, treatment satisfaction, response to treatment and safety during Ixazomib-Lenalidomide-Dexamethasone (IRd) treatment as ≥ 2nd line in RRMM pts in a real world setting. Adult pts with RRMM who have been assigned IRd as ≥2nd line treatment were enrolled in multicenter observational prospective study. Treatment response was evaluated by IMWG 2011, adverse events (AEs) - by CTCAE v.4.0. Pts filled out RAND SF-36 and ESAS-R at baseline and at 1 and 3 mos, and thereafter every 3 mos till 18 mos after IRd treatment start; Patient Treatment Satisfaction Cheklist (PTSC) - at each time-point after IRd treatment start. For analysis of meaningful QoL changes during IRd treatment the proportion of pts with baseline significant QoL impairment who experienced meaningful QoL improvement during IRd treatment was evaluated as well as the number of pts without baseline QoL impairment who maintained it during IRd treatment. For statistical analysis GLM paired test and GEE were employed with adjustment to age, gender and baseline QoL. In total, 40 pts with RRMM were enrolled into the pilot study: median age - 64 years (range, 33-80), 29% males, Durie-Salmon stage at study entry: I/II/III - 3/41/56%, ECOG status 0/1 - 68.7%, 2/3 - 31.6%. Median time since initial MM diagnosis - 51.4 mos (range, 2.9-100.7), disease status at study entry: relapsed - 26%, refractory - 21%, relapsed and refractory - 53%. Median number of lines of prior therapy is 3 (range, 1-3). At the time of analysis the median number of IRd cycles administered is 5, median follow-up - 4.6 (0.4-13.7) mos. Treatment response was not evaluated in 11 pts: 1 - death (at 3 months), 1- refusal, 9 - too early for evaluation. Out from 29 pts one patient achieved complete response (CR), seven pts achieved partial response (PR) and one patient - very good partial response (VGPR), 12 - minor response (MR). Thus, a clinical benefit rate was 70%. Also, seven pts achieved stable disease (23%), one patient was primary refractory to IRd (3.5%), one patient died (3.5%). At the time of analysis all the pts with CR/PR/VGPR (30%) maintained their response to treatment, 4 pts (13%) maintained stable disease and 9 pts (30%) maintained minor response; 7 pts (23%) experienced disease progression. AEs were revealed in 47% pts: grades 1-2 AEs - 12 pts; grades 3-4 AEs - 4 pts; SAEs - 3 pts (neurological toxicity, gastric bleeding, hypotension), all pts with SAEs discontinued IRd treatment. Baseline QoL was dramatically impaired by the majority of SF-36 scales with significant QoL impairment in 42% pts. The most worsening was revealed for physical functioning, role functioning, general health and vitality (Mean scores varied from 24.6 to 47.0 out from 100 scores). At baseline 88% pts had moderate-to severe symptoms (≥4 scores on the scale from 0 to 10); moderate-to severe worse wellbeing, tiredness, pain and shortness of breath had 72,5%, 67,5%, 61,5% and 45% pts, respectively. At 1 month of IRd treatment QoL meaningfully improved or was stable without significant impairment in 61% pts, at 3 months - in 50% pts. In 1 mos of IRd treatment significant improvement was revealed for physical functioning (GLM, 44.9 vs 54.7, p=.01) and general health (GLM, 47.8 vs 56.3, p<.001). Further during IRd treatment no significant QoL worsening was identified (GEE, p>.05). At 1 month of treatment, meaningful decrease of shortness of breath (in 42% pts), tiredness (36%), and pain (28%) was revealed; at 3 months of IRd treatment this proportion was 33%, 27%, and 13%, accordingly. Regarding treatment satisfaction pts reported the following: at 1 month after treatment start 94% of pts were satisfied with symptoms decrease due to IRd, 89% pts confirmed that IRd was convenient and 97% pts reported global satisfaction with IRd; at 3 months of treatment all the pts confirmed the convenience of IRd regimen, 84% pts were satisfied with IRd treatment. The results obtained in a real-world setting demonstrate clinical benefits of IRd regimen in RRMM pts, which were achieved without negatively affecting QoL and with satisfactory symptom control in these heavily pretreated patients. IISR funded by Takeda Disclosures Ionova: BMS: Research Funding; Takeda: Research Funding. Vinogradova:Novartis: Honoraria, Research Funding.

At present there is no cure for RRMM, yet pts have prolonged survival due to improved treatments, and therefore ensuring acceptable QoL throughout treatment is worthwhile. We aimed to evaluate QoL, safety and response to treatment with IRd as ≥ 2nd line in RRMM pts in a real world setting. Adult pts with RRMM who have been assigned IRd as ≥2nd line treatment were enrolled in multicenter observational prospective study. Treatment response was evaluated by IMWG 2011, adverse events (AEs) – by CTCAE v.4.0. Pts filled out SF-36 and ESAS-R at baseline and during IRd treatment. Descriptive statistics and paired t-test were employed. At time of analysis 32 pts with RRMM were enrolled: median age – 65 yrs, 72% females, Durie–Salmon stage III – 56%, ECOG status 2/3 – 28%. Half of pts had 3-7 lines of prior therapy. The median number of cycles administered is 4, median follow-up – 4.5 (0.4-10.5) mos. Treatment response was not evaluated in 9 pts: 1 – death (at 3 months), 1– refusal, 7 – too early for evaluation. Out of 23 pts 6 achieved partial response, 10 – minor response, yielding a clinical benefit rate of 67%. AEs were revealed in 43% pts: grades 1-2 AEs – 9 pts; grades 3-4 AEs – 4 pts; SAEs – 3 pts (neurological toxicity, gastric bleeding, hypotension). Baseline QoL was dramatically impaired by the majority of SF-36 scales with significant QoL impairment in 50% pts. 88% pts had moderate-to severe symptoms (≥4 scores on the scale from 0 to 10); moderate-to severe tiredness, pain or shortness of breath had 72%, 59% and 50% pts, respectively. At 1 month of IRd treatment QoL improved or was stable (without significant impairment) in 53% pts, at 3 months – in 45% pts. Better general and mental health were observed 1 month after treatment start (p=0.01). At 1 month of treatment meaningful decrease of shortness of breath (in 60% pts), tiredness and pain (in 30% pts) was revealed; this proportion decreased twice at 3 months. The first results of our real-world study demonstrate significant clinical benefits of IRd regimen in RRMM pts. The treatment has acceptable safety profile and is accompanied with QoL maintenance and satisfactory symptom control in this heavily pretreated patients' cohort.

The aim of the study was to evaluate the quality of life (QoL) and symptoms in patients with myelofibrosis (MF). 93 patients with MF who participated in the multicenter observational study “Quality of life and symptoms in myelofibrosis: validation of the symptom assessment tool for patients with myelofibrosis” (2014–2015) were enrolled in the analysis. 62 patients received best available treatment (BAT) and 31 patients received ruxolitinib. All the patients filled out the SF-36, CSP-Myelofibrosis Module and Patient Global Impression of Change (PGIC) tools. In the real-world study in MF patients QoL was demonstrated to be significantly worse than in healthy controls; more than one third of patients had significant or severe QoL impairment. Patients treated with ruxolitinib had better QoL and lower symptom severity as compared to BAT patients. Decline of activity appeared to be the major symptom which significantly reduced QoL in MF patients. QoL and symptom data in MF patients during treatment in a real world setting may be a solid supplement to clinical variables and may contribute to better disease control in accordance with the principles of risk-adaptive therapy.

Introduction: Over the past decades, different medicinal products have been used for treatment of multiple myeloma in clinical studies, including new generations of proteasome inhibitors and immunomodulating agents, monoclonal antibodies, histone deacetylase inhibitors etc. The use of these treatment modalities results in improvement of overall survival (OS). However, taking into account high cost of these drugs, their availability in real clinical practice remains limited.

The aim of the study was to evaluate the quality of life (QoL) and symptoms in patients with myelofibrosis (MF). 93 patients with MF who participated in the multicenter observational study "Quality of life and symptoms in myelofibrosis: validation of the symptom assessment tool for patients with myelofibrosis' (2014-2015) were enrolled in the analysis. 62 patients received best available treatment (BAT) and 31 patients received ruxolitinib. All the patients filled out the SF-36, CSP-Myelofibrosis Module and Patient Global Impression of Change (PGIC) tools. In the real-world study in MF patients QoL was demonstrated to be significantly worse than in healthy controls; more than one third of patients had significant or severe QoL impairment. Patients treated with ruxolitinib had better QoL and lower symptom severity as compared to BAT patients. Decline of activity appeared to be the major symptom which significantly reduced QoL in MF patients. QoL and symptom data in MF patients during treatment in a real worldsetting may be a solid supplement to clinical variables and may contribute to better disease control in accordance with the principles of risk-adaptive therapy.

Background: The greatest progress in treatment of lymphoproliferative malignancy multiple myeloma (MM) was achieved in the past decade. According to population studies, in the last decade 5-year overall survival (OS) rate in patients (pts) with MM in the Germany was 39%, in the USA - 47%.

Abstract Introduction. The vast majority of AML clinical trials incorporate high-dose ARA-C (HDARA-C) as a basic approach. Though it was recently proved by a controlled prospective comparison that different treatment strategies in patients with AML did not show clinically relevant outcome differences (Th.Buchner, JCO, 2012), the RALSG initiated a randomized multicenter AML-10 trial (ClinicalTrials.gov Identifier: NCT01587430) aiming to evaluate the necessity of HDARA-C in consolidation in the context of high total dose of different anthracyclines/anthracenedione (660-720 mg/m2). Materials and methods. The patients aged 16-60 yy with de novo AML (except APL) were randomized before treatment start to different types of consolidation after two induction 7+3 with daunorubicin 60 mg/m2x3 and ARA-C 100 mg/m2 bid iv (1-7d) in the 1st course and 200 mg/m2/d (1-7d) continuous infusion in the 2nd course: (1st arm) two courses of 7+3 with Idarubicin (Ida) 12 mg/m2x3 and with Mitoxantrone (Mito) 10 mg/m2x3, in both ARA-C 100 mg/m2 bid iv (1-7d); (2nd arm) two courses of HDARA-C 1g/m2 bid iv 1-3 days with Ida 8 mg/m2 3-5 days and Mito10 mg/m2 3-5 days. After consolidation all pts proceeded to the maintenance 5+5 courses (ARA-C 100 mg/m2 bid iv 1-5 days with 6-mercaptopurine 50 mg/m2 1-5 days). Allogeneic HSCT was indicated to patients from intermediate and poor cytogenetic risk groups, late CR, WBC > 100*109/l. Results. From Jan 2010 till Jan 2014, 250 AML patients from 20 centers were randomized: (1st arm) 125 pts (m.age 45 y, 17-59 yy; 73f / 52m; LDH=674 IU (128-6653); cytogenetics favorable - 17,3%, intermediate - 66,7%, poor - 16%) and (2nd arm) 125 pts (m.age 43y, 16-60yy; 69f/56m; LDH=704 IU (123-8159); cytogenetics favorable - 20%, intermediate - 58,6%, poor - 21,4%). No molecular testing in cytogenetically normal pts was done. The analysis was performed in May 2014. The follow-up data were available in 199 pts. CR was achieved in 72,9% (n=145), early death was registered in 12,7% (n=25) and refractory disease - in 12,4% (n=24). Death in CR did not differed in a randomized groups (1st) 13,9% and (2nd) 13,7%. 17% of CR pts (n=20) were withdrawn from the protocol due to refusals (3,5%), infectious complications (13,5%). No relevant cardiotoxicity was registered on both arms. 12% (8 pts on the 1st arm, 9 - on the 2nd) were transplanted in 1st CR from HLA-identical donors. 3-years OS and DFS by intent-to-treat analysis were identical on both arms: (1st arm) 43% and 62%, (2nd arm) - 38% and 51%, respectively. For those patients in whom consolidation was fulfilled the comparison of DFS in different cytogenetic groups demonstrated equal efficacy of each consolidation arm: favorable - 85% (1st) and 85% (2nd), intermediate -65% (1st) and 57% (2nd), poor - 20% (1st) and 22% (2nd). In a multivariate analysis only cytogenetic group (HR=3,01, p=0,005) and CR achievement after the 2nd induction course (HR=2,83, p=0,0007) adversely influenced DFS. As the land-mark (5 mo of CR) analysis have shown, the bad prognosis of late CR could be modified by allo-HSCT in 1st CR: DFS of transplanted patients = 86%, non-transplanted=27% (p=0,03). Conclusion. Our interim analysis has demonstrated that conventional 7+3 consolidation is equal in long-term outcome to high dose ARA-C in case of the high total doses of different anthracyclines/ anthracenedione in induction/consolidation. CR after the 2nd induction became independent adverse prognostic factor (even inside cytogenetic risk groups) defining patients who should be transplanted in 1st CR. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.