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: Chronic primary immune thrombocytopenia (cITP) is a rare autoimmune disease which needs lifelong therapy to prevent bleeding and is accompanied with impaired quality of life (QoL) due to hemorrhagic syndrome, psychological concerns and limitations in patients’ daily life. Fatigue with its negative impact on QoL is of tremendous concern for patients with cITP. Aims: We aimed to explore QoL and fatigue changes as well as to examine platelet response in patients with cITP during treatment with romiplostim in a real-world setting. Methods: Adult patients with cITP who have been assigned romiplostim treatment were enrolled in multicenter observational prospective study. Romiplostim was administered in accordance with prescription. Patients filled out RAND SF-36 and FACT-Th6 questionnaires for QoL assessment and FACIT-Fatigue tool for fatigue assessment at baseline and at 3, 6 and 12 months after romiplostim treatment start. Fatigue level was categorized according to the quartiles of the FACIT-Fatigue scores as follows: low (Q4, 40-52), low-medium (Q3, 27-39), medium-high (Q2, 14-26), or high (Q1, 0-13). For statistical analysis of patient-reported outcomes (PRO) Mann-Whitney test, GEE and MacNemar test were applied. Adjustment to age, gender, severity of cITP and baseline QoL/fatigue for GEE was made. Kaplan-Meyer method was used to measure time till the first platelet response from romiplostim treatment start. Results: In total, 60 patients with cITP from 17 centers in Russia were enrolled in the study: mean age – 51.9±15.4 (range, 25-85); 70% were females; 71.7% patients had comorbidities. Four patients were splenectomized (6.7%). Median of disease duration was 25.1 months (range, 12.6-765.1). Majority of patients experienced hemorrhagic syndrome (96.7%). Median platelet count before romiplostim was 20 х109/l. Median number of treatments before romiplostim was 1 (range, 0-6). At baseline cITP patients experienced meaningful QoL impairment by all SF-36 scales excluding pain as compared to healthy controls (p<0.05). Integral QoL index was 0.285 for patients vs 0.432 for healthy controls (p<0.001); 39% patients had critical/severe QoL impairment before romiplostim onset. Mean FACT-Th6 score was 11.2±5.5 (range, 0-22). Мean FACIT-Fatigue score was 33.0±10.2 (range, 7–49); 22.4% of patients had high/medium-high level of fatigue. At median follow-up of 9.7 months (IQR, 7.2–12), 98.3% patients achieved overall platelet response; median time to first platelet response was 4 weeks (95%CI: 3–5). Median platelet count at 3 months of treatment was 104 х109/l. During 12 months of romiplostim treatment dramatic meaningful QoL improvement by all SF-36 scales (GEE, p<0.001) and by FACT-Th6 score (GEE, 11.4 at baseline vs 17.1 at 12 months, p<0.001) was demonstrated. Fatigue severity reduced during romiplostim treatment: FACIT-Fatigue score increased from 33.1 at baseline to 42.7 at 12 months (GEE, p<0.001); the number of patients with high/medium-high level of fatigue significantly decreased from 22.4% at baseline to 6.8% after 3 months of treatment (p=0.01). Summary/Conclusion: The results obtained demonstrated high response rates to romiplostim treatment in cITP patients and significant positive changes in QoL and fatigue level during therapy in a real-world evidence study. Benefits of romiplostim treatment was confirmed both from physician’s and patient’s perspective.

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.

Хронический миелолейкоз (ХМЛ) — редкое заболевание, число впервые выявленных больных которым в год составляет приблизительно 1 : 100 000 населения. В Российской Федерации в настоящее время насчитывается около семи тысяч больных ХМЛ. Внедрение в течение последнего десятилетия в клиническую практику препаратов, направленно блокирующих активность опухолевой тирозинкиназы BCRABL изменило прогноз у больных ХМЛ, увеличило выживаемость больных с 3–4 лет до более 15 лет, привело к полному восстановлению трудоспособности с перспективой отмены терапии у значительной части больных. Настоящие клинические рекомендации представляют собой разработанный на основании принципов доказательной медицины протокол, включающий все этапы диагностики и терапии больных с хроническим миелолейкозом, в том числе мониторирования минимальной остаточной болезни. Предназначены для врачей-гематологов, онкологов, педиатров, организаторов здравоохранения.