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: Patients with Philadelphia-negative myeloproliferative neoplasms (MPNs), including myelofibrosis (MF), polycythemia vera (PV) and essential thrombocythemia (ET), experience troublesome symptoms leading to impaired functioning (physical and psychosocial) and quality of life (QoL). Understanding symptom burden, QoL and unmet patient needs across disease subgroups is of value to aid optimal treatment and rehabilitation decision-making for patients with different MPNs. It is also worthy to explore perceptions on the impact of the disease and its treatment among MPN patients and hematologists to ensure patient-centered care. Aims: The national survey MPN-QoL-2020 was aimed to evaluate QoL and symptom burden in patients with MPN, as well as to examine the perceptions of patients and physicians about the impact of MPN and its treatment in a real world setting in Russia. Methods: A survey of patients with MPN and their treating physicians was conducted from September to December 2020. This survey included in- or out-patients aged ≥18 years with a confirmed diagnosis of MF, PV, or ET. All the patients completed the HM-PRO, a hematological malignancy (HM) specific patient-reported outcomes (PRO) measure, the MPN10 symptom assessment tool, and a patient’s survey checklist. The HM-PRO consists of two scales: Part A measuring the ‘impact on patients’ QoL’; Part B measuring ‘signs and symptoms’ experienced by the patients. Part A has 4 domains: physical behaviour (PB), social well-being (SW), emotional behaviour (EB) and eating and drinking habits (ED). Physicians completed a physician’s survey checklist which included a record for each patient. Both paper and electronic versions of the survey forms were available. ANOVA and χ2 test were applied to examine the differences between groups. Results: 1100 patients with MPNs (MF, n=355, PV, n= 408 and ET, n=337; mean age = 58±14 yrs; female = 61%) and 100 hematologists (mean age = 42±12 yrs, female = 85%) from 37 medical centers completed the survey. The HM-PRO Parts A & B total scores were significantly worse (higher scores) in MF and PV patients than in ET (Table 1). Impact on PB and EB was higher in MF and PV as compared to ET: PB = 28.6 and 21.4 vs 14.3; EB = 31.8 and 27.3 vs 22.7, respectively. Impact on ED was higher in MF as compared to PV and ET. SF was less impaired and similar across different MPNs. Among MF there were more patients with moderate/large effect on QoL as compared to PV and ET – 40% vs 34% and 28% (p=0.003). The vast majority of MPN patients experienced symptoms (95%); more than 80% had fatigue and inactivity. The MPN10 Total Symptom Score was the highest in MF, intermediate in PV and the lowest in ET: 24 vs 20 vs 14 (p<0.001). Notably, 29% MF, 34% PV and 44% ET patients did not attribute their symptoms to MPN. Physicians and patients had a discordant perspective of the most bothersome symptoms. There was agreement between MF patients and their physicians about the impact of the disease on QoL and symptom burden. For PV and ET, physicians underestimated patient’s concerns; the discrepancies were pronounced for QoL impact (PV, p=0.028; ET, p<0.001) and symptom burden (PV, p=0.018; ET, p<0.001). Across MPNs, 41.5% MF, 37.8% PV and 35.2% ET agreed that there were areas of patient-physician relationship needed to be improved. Image:Summary/Conclusion: The findings of this nationwide survey demonstrate differences in the impact on QoL and symptom burden across MPNs, identify the areas of different perspective between patients and physicians about MPN and its treatment as well as highlight the unmet needs among patients with MPN.

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.

Background:Ruxolitinib(RUXO) improves long‐term prognosis in patients(pts) with primary or post‐polycythemia/post‐thrombocythemia myelofibrosis(MF). The most patients experience spleen response. Meanwhile there are a few data how the speed of spleen response in MF affects RUXO treatment outcome.Aims:Evaluate prognostic significance of early spleen response on results of RUXO treatment in patients with MF and assess the factors associated with spleen response.Methods:In the multicenter real world ptactice study 42 patients (male 18, 43%) with MF and spleen data available at least at 3 months were included. Median age at the time of RUXO initiation was 55(25‐75)yrs. Median time from MF diagnosis to RUXO was 52(2‐346)mos. Median time on RUXO was 29 (4‐81)mos. Spleen response(SR) was assessed by palpation. Median spleen length before RUXO was 19(5‐33 cm) with massive spleen >10 cm in the most pts ‐ 36(86%). Constitutional symptoms had 40(95%) of pts. DIPSS score was low, inter‐1 or inter‐2/high in 1(3%), 23(59%) and 15(38%) of 39 evaluable pts.Results:Spleen length reduction at 3mos was: <25% in 13(31%)(Group 1), 25‐<50% in 14(33%) (Group 2) and ≥50% in 15(36%)(Group 3) pts. At 6 mos 3/12(25%) and 3/14(21%) evaluable pts from Gr1 and Gr2 improved their SR. Some more pts from these groups experienced spleen reduction later, but mainly in case of RUXO dose elevation. SR, assessed according to IWG‐MRT criteria, was 13/42(31%) and 17/41(41,5%) in evaluable pts at 3mos and 6 mos, respectively. In all groups a few pts lost their SR. RUXO was stopped in 11(26%) pts, mainly due to disease progression or/and death. Depth of sSR significantly correlated with overall survival. All pts of Gr3 remained alive, whereas 7/29(24%) pts dead in Gr2 and Gr3 overall(p = 0,021). Less pts in Gr3 had huge spleen(>20 cm), blasts 1% or more, low hemoglobin and were treated with low RUXO dose. There were equal symptoms burden in in different groups (Table 1).Summary/Conclusion:The majority of pts respond to RUXO. Depth of SR at 3 mos significantly influenced RUXO long term outcome – all pts with >50% of spleen reduction at 3 mos are alive. It seems that pts with higher dose of RUXO, no periferal blasts, less spleen size and higher hemoglobin level are more responded to RUXO. Larger cohort of pts is needed to confirm statistical significance of this data.image