Functional Assessment Of Cancer Therapy-Anemia Research Articles

Improvement of Patient-Reported Outcomes Among Heavily Pretreated Patients with Lower-Risk Myelodysplastic Syndromes and High Transfusion Burden Treated with Imetelstat on the IMerge Phase 3 Trial

CONCLUSIONS Transfusion-dependent anemia and related fatigue are commonly associated with lower-risk myelodysplastic syndromes (LR-MDS) and frequently not improved with therapy. Patients with symptoms associated with anemia have an impaired quality of life and inferior overall survival. In IMerge (NCT02598661), the phase 3, randomized, global trial of patients with LR-MDS and a red blood cell transfusion burden of ≥4 U, imetelstat-treated patients had a significantly higher transfusion independence rate than those treated with placebo and showed sustained improvement in patient-reported fatigue via the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue (Sekeres et al. EHA 2023. P732). Here, we assess the impact of imetelstat on several patient-reported outcomes (PROs) relevant to LR-MDS. Functional Assessment of Cancer Therapy-Anemia (FACT-An; 55 items) and Quality of Life in Myelodysplasia Scale (QUALMS; 38 items) were the main questionnaires used. Analyses included symptom-specific derived scores for the following parameters: dyspnea, measured by 1 FACT-An and 1 QUALMS item; physical function and systemic symptoms, by 3 FACT-An items each; pain, by 2 FACT-An items; and bleeding, by 1 QUALMS item. Higher scores indicated improvement. QUALMS total score and physical burden score were also analyzed. Psychometric analyses were conducted using blinded interim data to document the measurement properties of these item sets and define the scores that would be used to specify PRO end points in IMerge; all analyses were exploratory and were conducted in the intention-to-treat (ITT) population. The overall effect of imetelstat on each score was evaluated from the repeated measurement mixed model (RMMM) comparing the least-squares means (LSMs) of change in score estimated in the 2 treatment groups using all available data while on treatment up to cycle 30. A positive mean change in the dyspnea score was observed throughout the treatment, up to cycle 24, in the imetelstat group but not in the placebo group (Figure). The RMMM analysis showed an overall change in dyspnea score from baseline of 0.53 (by LSM with 95% CI, 0.241-0.825) with imetelstat versus −0.40 (by LSM with 95% CI, −0.794 to 0.003) with placebo, with a significant difference between the treatment groups (LSM difference, 0.93; 95% CI, 0.446-1.411; P < .001; Table). The model-based mean change estimates for each score showed that, despite having high transfusion burden at baseline, patients in the imetelstat group did not experience more deterioration in any of the other outcomes than those in the placebo group (Table). In addition, the QUALMS composite scores suggested significantly improved health outcomes with imetelstat versus placebo based on RMMM. LSM difference was 4.66 (95%CI, 0.862-8.461; P = .016) and 6.34 (95% CI, 1.771-10.913; P = .007) for QUALMS total and QUALMS physical burden, respectively (Table). Findings from multiple validated PRO questionnaires consistently show that patients with red blood cell transfusion-dependent LR-MDS enrolled into the IMerge randomized trial who were treated with imetelstat reported improved fatigue, dyspnea, and QUALMS composite scores (total and physical burden) compared with those in the placebo group. These data indicate that, in addition to improving transfusion burden in patients with LR-MDS, imetelstat targets multiple core symptoms of LR-MDS simultaneously, also improving PROs.

Patient-Reported Outcomes (PRO) of Luspatercept Versus Epoetin Alfa in Erythropoiesis-Stimulating Agent (ESA)-Naïve, Transfusion-Dependent (TD), Lower-Risk Myelodysplastic Syndromes (LR-MDS): Results from the Phase 3 COMMANDS Study

Background: For symptomatic anemia in patients with LR-MDS, supportive treatment with erythropoietin stimulating agents (ESAs), such as epoetin alfa, remains the current standard of care, which has limited and transient effect. The phase 3, open-label, randomized, controlled COMMANDS study demonstrated that luspatercept significantly improved the rate of transfusion independence and hemoglobin levels, when compared to epoetin alfa in ESA-naïve and transfusion-dependent (TD) patients with LR-MDS (Platzbecker U, et al. Lancet. 2023;S0140-6736(23)00874-7). Objective: The objective of this interim analysis was to assess the effect of luspatercept versus epoetin alfa on patient-reported outcome (PRO) using data from the first 24 weeks of the COMMANDS study. Methods: In COMMANDS, 356 patients were randomized 1:1 to luspatercept (Q3W) or epoetin alfa (QW). PROs, as one of the secondary objectives, were assessed by the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire - Core 30 (EORTC QLQ-C30) and the Functional Assessment of Cancer Therapy - Anemia (FACT-An) questionnaire.The EORTC QLQ-C30 was assessed on Day 1 prior to the first dose (baseline) and every 6 weeks thereafter; the FACT-An was administered at baseline, weekly for 3 weeks, and then every 3 weeks thereafter. Time to sustained improvement on domains of the EORTC QLQ-C30 and FACT-An was assessed between treatment arms using a stratified Cox proportional hazards regression model. Sustained improvement was defined as improvement from baseline ≥ pre-specified responder definition, sustained for at least 42 days through Week 25 Day 1 (W25D1). Overall treatment tolerability, assessed by the FACT-An item GP5 (“I am bothered by side effects of treatment”), was descriptively summarized at W25D1 by treatment arm. All analyses were conducted on the respective PRO-evaluable populations for each instrument, including patients who had completed the assessment at baseline and at least one post-baseline visit, unless otherwise specified. Results: The EORTC QLQ-C30 evaluable population consisted of 150 and 144 patients randomized to luspatercept and epoetin alfa, respectively (median age 74.5 years and 54% male). Population sizes were similar for other PRO measures. Demographics, disease characteristics, and PRO domain scores at baseline were generally comparable between treatment arms. Completion rates of PRO assessments were moderately high for both arms (approximately 70-90%) through the W25D1 visit. Luspatercept resulted in a higher probability of sustained improvement through W25D1 in almost all domains of the EORTC QLQ-C30 and FACT-An compared to epoetin alfa, with significant differences (nominal p-value <0.05) in dyspnea (hazard ratio [HR] [95% confidence interval]: 3.18 [1.03, 9.81]) and 7 other domains of the EORTC QLQ-C30 (role functioning, cognitive functioning, pain, insomnia, appetite loss, constipation, and financial difficulties). Patients in both arms experienced similar overall treatment tolerability, with >67% of all patients still on treatment reporting to be “not at all” bothered by treatment side effects through W25D1. Conclusions: The findings from these interim PRO analyses indicate that treatment with luspatercept increased sustained improvement across quality-of-life domains when compared to epoetin alfa. Luspatercept was also found to be well-tolerated by the majority of patients. All of these PRO findings further support the benefits of luspatercept in ESA-naïve and TD patients with LR-MDS.

Understanding the Association between Red Blood Cell Transfusion Utilization and Humanistic and Economic Burden in Patients with β-Thalassemia from the Patients' Perspective.

We assessed the humanistic and economic burden of chronic red blood cell (RBC) transfusions on patients with β-thalassemia. This cross-sectional, US-based study included adults (≥18 years) who self-reported a β-thalassemia physician diagnosis and had received ≥1 RBC transfusion in the past 6 months. The outcomes included the Functional Assessment of Cancer Therapy-Anemia (FACT-An), Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and ad hoc questions about treatment experience, side effects, direct/indirect costs, and psychological burden. Overall, 100 patients completed the survey, of whom 70% experienced "moderate" to "extremely high" burden due to RBC transfusions, 81% reported iron overload, 42% reported compromised social lives. The mean FACT-An score was 132 (higher score indicates better outcomes; 0-188). Mean scores were 33/52 for fatigue and 20/28 for anemia symptoms in the previous 7 days. Health-related quality of life (HRQoL) temporarily improved after RBC transfusion, although patients continued to experience mild-to-severe depression and anxiety, substantial direct costs, compromised employment, and suboptimal quality of life. Over 6 months, patients dedicated a mean of 173 h to transfusion requirements and incurred out-of-pocket costs of USD 2239 for transfusions and USD 896 for additional care costs. These findings highlight the need for new treatment options to improve patient HRQoL and economic outcomes.

The Launch of Two Sub-Studies of the Peak Registry, a Global, Longitudinal Study of Pyruvate Kinase Deficiency

Background: Pyruvate kinase (PK) deficiency is a rare, glycolytic enzymopathy caused by autosomal recessive mutations in the PKLR gene, which leads to lifelong hemolytic anemia and potentially serious complications such as extramedullary hematopoiesis, pulmonary hypertension, and iron overload. The Peak Registry (NCT03481738) was initiated in 2018 as a global, retrospective and prospective, observational study of pediatric and adult patients with a genetically confirmed diagnosis of PK deficiency to better understand the natural history, treatment patterns, and burden of disease. The registry aims to enroll 500 patients at approximately 60 sites in up to 20 countries over 7 years, with at least 2 and up to 9 years of follow-up. In 2021, two sub-studies were initiated to obtain additional information on the patient experience with PK deficiency, with a specific focus on 1) patient-reported health-related quality of life, including impact on work productivity and activity impairment (NCT04964323) and 2) the impact of PK deficiency on cognitive performance (NCT04995315). Unlike the core registry where data reporting is managed by sites via electronic case report forms, the sub-studies utilize an innovative decentralized design. The core registry and both sub-studies are currently open for enrollment. Methods: The design of the core registry has been previously described1. Both sub-studies are managed via a decentralized model using a web-based portal (N of 1 Health Research Platform; Digital Infuzion, Inc.). The patient-reported outcomes sub-study is open to adult (≥18 years) Peak participants in the US, Netherlands, Italy, Spain, and the UK with a target enrollment of 75 patients. Assessments include the PK Deficiency Diary (PKDD), PK Deficiency Impact Assessment (PKDIA), Functional Assessment of Cancer Therapy-Anemia (FACT-An, anemia subscale only), and the Work Productivity and Activity Impairment (WPAI) questionnaire. All assessments are completed electronically (computer, tablet, or mobile phone) at baseline and every 3 months thereafter (every 6 months for PKDD) over a 24-month period. The cognition sub-study is open to adult Peak participants in the US, Netherlands, and Italy with a target enrollment of 33 patients. Participants are required to use a desktop computer or laptop to complete a battery of self-administered cognitive assessments of psychomotor speed, attention, visual learning, and working memory utilizing the Cogstate Brief Battery (CBB). The assessments are completed at baseline and Day 90. Eligible patients can opt into sub-study participation through the platform's online Peak Patient Community Portal and begin the informed consent form (ICF) process which is managed by regional coordinating centers in each respective country. Once the ICF process has been completed, participants have access to the study surveys via the online portal. Data collected from both sub-studies will be summarized descriptively. Ethics approval has been received from all participating countries, and all stored data is de-identified. Results: Sites in the US were approved for sub-study enrollment on a rolling basis between July 2021 and May 2022, and had enrolled 5 patients as of 07Jul2022. Enrollment opened in Spain in April 2022, the Netherlands in May 2022, and in Italy and the UK in July 2022. As of 07Jul2022, 252 patients had enrolled in the core registry, of whom approximately 100 are adults in countries participating in the sub-studies and thus potentially eligible for sub-study participation. Summary: The Peak Registry provides a unique and impactful opportunity to enhance our understanding of PK deficiency. Two complementary sub-studies on health-related quality of life and cognition have recently been developed to obtain additional information on the patient experience with PK deficiency that has not been systematically captured or reported elsewhere. Further information is available at https://peakregistry.com and www.clinicaltrials.gov, and from medinfo@agios.com. 1Grace RF et al. Blood (2019) 134 (Supplement_1): 2223.

Impact of Iron-Deficiency Management on Quality of Life in Patients with Cancer: A Prospective Cohort Study (CAMARA Study)

BackgroundIron deficiency (ID) is very common in patients with solid tumors and may cause symptoms such as fatigue. However, its impact on clinical outcomes is poorly described. The aim of this prospective monocentric cohort study was to evaluate the evolution of quality of life (QoL) of these patients after iron supplementation.MethodsWe included patients treated for a solid tumor, which were diagnosed with a functional (ferritin <800 ng/mL) or absolute (ferritin <300 ng/mL) ID (transferrin saturation coefficient <20%). The primary endpoint was patients’ QoL evolution between baseline and intermediate visit, 15-30 days after initial intravenous iron supplementation, assessed by the Functional Assessment of Cancer Therapy-Anemia (FACT-An) scale. Secondary endpoints were the same assessment between baseline, intermediate, and final visit at 6 months and the evolution of functional capacities.ResultsFrom 02/2014 to 12/2016, 248 patients were enrolled, of whom 186 were included in the analyses, including 140/186 (75.3%) with absolute ID. Anemia was detected in 141/174 (81.0%) patients at baseline. The FACT-An scores improved significantly between inclusion and intermediate visit (P = .001) and also between the 3 times of evaluation (P < .001). The most improved dimensions were those assessing physical, emotional well-being, and fatigue. Patients who performed the functional tests in all 3 phases had a significant improvement in performance on the majority of tests.ConclusionThe supplementation of ID was associated with an improvement of the QoL and functional capacities in patients with cancer. A randomized control trial is necessary to confirm our results. Our findings underline the importance of supportive care, including screening for ID, in oncology.Clinical trial registration numberNCT03625661.

Understanding the Association between Red Blood Cell Transfusion Dependency and Humanistic, Psychosocial, and Psychological Burden in Patients with β-Thalassemia from the Patients' Perspective

Introduction: A recent systematic literature review (Betts M, et al . Clin Ther 2020;42:322-337) perceived that in the past 2 decades, advancements in the treatment and management of β-thalassemia have resulted in improvements in iron control. However, clinical complications, including alloimmunization, iron overload, and resultant cardiac and liver disease, remain a challenge. While red blood cell (RBC) transfusions are used to treat anemia in patients with β-thalassemia, those who are transfusion dependent reported poorer health-related quality of life (HRQoL) compared with the US general population. The literature misses a holistic understanding of the humanistic, psychosocial, and psychological burden of transfusion dependency in β-thalassemia in terms of the impact of disease and treatment on patients' daily lives, distress arising from the possibility of adverse events, and comorbidities.Methods: First, concept elicitation qualitative interviews (n=3) and cognitive pre-test interviews (n=3) were conducted with patients from the Cooley's Anemia Foundation (CAF) to test and revise a 30-minute web-based patient survey questionnaire for clarity and relevance. Following, a larger cross-sectional study included adult patients with β-thalassemia in the USA identified by the CAF. Patients were recruited via email invitation or social media, and invited by CAF to take the survey, at which point informed consent was obtained. Inclusion criteria included ≥18 years of age, self-reported physician diagnosis of β-thalassemia, and ≥1 RBC transfusion in the past 6 months. Survey instruments included the Functional Assessment of Cancer Therapy-Anemia (FACT-An), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), ad hoc questions around patient treatment experience, side effects resulting from β-thalassemia treatment, and psychological burden due to treatment. All results were reported descriptively, with frequency counts and percentages for categorical/ordinal data and mean and standard deviations (SD) for continuous data.Results: Overall, 100 patients in the USA completed the survey; 65% were female, average age was 36.0 (SD=10.4) years, 42% were Asian/Pacific Islander, and 33% reported a household income of USD 100,000 or more. On average, patients had been diagnosed with β-thalassemia for 34.4 (SD=10.3) years and received 9.6 (SD=4.3) RBC transfusions in the past 6 months. Among all patients, 70% reported moderate to extremely high burden of RBC transfusions, 81% reported experiencing iron overload due to RBC transfusion, and 42% reported not being as social with friends/family due to the time needed for RBC transfusions and the associated recovery time. Over 50% of patients reported mild to severe depression (52%) via PHQ-9 and anxiety (53%) via GAD-7 symptoms over the previous 2 weeks. The FACT-An (0-188), where higher scores indicate better outcomes, average score was 132 (SD=33.5), while fatigue symptoms (0-52) average score was 33.3 (SD=12.3), and anemia symptoms (0-28) average score was 20.4 (SD=5.5) in the past 7 days. A week prior to receiving an RBC transfusion, 18% of patients reported their overall health as “very well” versus 52% 1 week after an RBC transfusion.Conclusions: Although upon RBC transfusion HRQoL temporarily improves, overall, these results demonstrated patients with transfusion-dependent β-thalassemia experienced poor health prior to RBC transfusion, mild to severe depression and anxiety, increased psychological burden, and suboptimal HRQoL. These findings contribute to the understanding of the humanistic and psychological burden of RBC transfusion dependency in patients with β-thalassemia and suggest that new treatment options that can improve outcomes in this population are needed. DisclosuresPrice: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Gupta: Bristol Myers Squibb: Consultancy, Research Funding; Kantar Health: Current Employment. Perkowski: Kantar Health: Current Employment; Bristol Myers Squibb: Consultancy, Research Funding. Costantino: Kantar Health: Current Employment; Bristol Myers Squibb: Consultancy, Research Funding. Inyart: Kantar Health: Current Employment; Bristol Myers Squibb: Consultancy, Research Funding. Ashka: Kantar Health: Current Employment; Bristol Myers Squibb: Consultancy, Research Funding. Clapp: Kantar Health: Current Employment; Bristol Myers Squibb: Consultancy, Research Funding. Knoth: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company.

Health-related quality of life and fatigue in children and adults with pyruvate kinase deficiency

AbstractPyruvate kinase deficiency (PKD) is the most common cause of congenital nonspherocytic hemolytic anemia. Although recognition of the disease spectrum has recently expanded, data describing its impact on health-related quality of life (HRQoL) are limited. In this prospective international cohort of 254 patients (131 adults and 123 children) with PKD, we used validated measures to assess the impact of disease on HRQoL (EuroQol 5-Dimension Questionnaire, Pediatric Quality of Life Inventory Generic Core Scale version 4.0, and Functional Assessment of Cancer Therapy-Anemia) and fatigue (Patient Reported Outcomes Measurement Information System Fatigue and Pediatric Functional Assessment of Chronic Illness Therapy-Fatigue). Significant variability in HRQoL and fatigue was reported for adults and children, although individual scores were stable over a 2-year interval. Although adults who were regularly transfused reported worse HRQoL and fatigue compared with those who were not (EuroQol-visual analog scale, 58 vs 80; P = .01), this difference was not seen in children. Regularly transfused adults reported lower physical, emotional, and functional well-being and more anemia symptoms. HRQoL and fatigue significantly differed in children by genotype, with the worst scores in those with 2 severe PKLR mutations; this difference was not seen in adults. However, iron chelation was associated with significantly worse HRQoL scores in children and adults. Pulmonary hypertension was also associated with significantly worse HRQoL. Additionally, 59% of adults and 35% of children reported that their jaundice upset them, identifying this as an important symptom for consideration. Although current treatments for PKD are limited to supportive care, new therapies are in clinical trials. Understanding the impact of PKD on HRQoL is important to assess the utility of these treatments. This trial was registered at www.clinicaltrials.gov as #NCT02053480.

The Effectiveness of a Nursing Care Program Supplemented with Iron Intake on Anemia and Fatigue in Cancer Patients Undergoing Chemotherapy

Background: Fatigue is one of the most common complications of cancer. Anemia can be one of the most prevalent causes of fatigue in cancer patients. Objectives: The present study aimed to explore the effectiveness of a nursing care program supplemented with iron intake on the anemia and fatigue in cancer patients undergoing chemotherapy. Methods: The present study was conducted in a quasi-experimental design on two groups of 90 cancer patients in selected hospitals. The participants were selected via convenience sampling and were randomly assigned to the control and intervention groups. Before the intervention, the Functional Assessment of Cancer Therapy - Anemia (FACT-An) was completed by the patients in both groups. The patients in the control group did not receive any special care other than receiving 150 mg of iron daily. However, the patients in the intervention group received 150 mg of iron daily and attended a nursing care program with four individual training sessions (one session per week). Follow-up was performed for three weeks, and the questionnaire was completed again by the participants in both groups. The collected data were analyzed using the independent samples t-test, paired-samples t-test, and chi-square test in SPSS software (version 22). The data analysis process was performed at a significance level of less than 0.05. Results: The mean scores for the patient hemoglobin in the intervention and control groups after the intervention were 11.84 ± 0.58 and 11.10 ± 67.29, showing a significant increase in favor of the intervention group (P &lt; 0.001). Furthermore, the results of the independent samples t-test showed that the mean score of fatigue for the patients in the intervention group (29.37 ± 9.56) was significantly lower than that of the participants in the control group (47.55 ± 11.22) (P &lt; 0.001). Conclusions: The present study showed that the implementation of a nursing care program for cancer patients receiving iron supplementation positively affects iron-related blood parameters and fatigue among these patients. Therefore, to control cancer patients' fatigue, medical staff must pay special attention to these training and care programs supplemented with iron intake.

Content validity of patient-reported outcomes for use in lower-risk myelodysplastic syndromes

BackgroundThe lower-risk (low and intermediate-1 risk based on IPSS) myelodysplastic syndrome (MDS) has a negative impact on patients’ health-related quality of life (HRQoL). Patient Reported Outcomes (PROs) instruments, which are used to collect patients’ HRQoL data, should have established content validity in the target population to ensure that the instrument is comprehensive and comprehensible. The present study was conducted to evaluate the content validity of the Quality of Life in Myelodysplasia Scale (QUALMS) and the Functional Assessment of Cancer Therapy-Anemia (FACT-An) PRO instruments in patients with lower-risk MDS.MethodsIn this cross-sectional, qualitative study, 16 patients aged ≥18 years with lower-risk MDS, who were RBC transfusion dependent, literate and fluent in US-English were interviewed. Interviews were semi-structured comprising of two parts: concept elicitation (CE) explored symptoms and impacts important to patients, and cognitive debriefing (CD) assessed understanding and relevance of the QUALMS and FACT-An. A conceptual model was developed, which was used to map the concepts that emerged during CE onto the QUALMS and FACT-An to assess concept coverage and suitability of the instruments.ResultsThe median age of participants was 67.5 years (range: 51–91), with half being female (n = 8). Nine (56.2%) participants had intermediate-1-risk MDS and 10 (62.5%) were relapsed or refractory to erythropoiesis-stimulating agent treatment. Fatigue/tiredness (100.0%), shortness of breath (87.5%), weakness (81.2%), and low energy (75.0%) were reported most commonly and were the most bothersome symptoms as well. Of seven high-level HRQoL domains identified, activities of daily living (n = 16, 100.0%), physical functioning (n = 15, 93.8%), emotional wellbeing (n = 13, 81.3%), social functioning (n = 12, 75.0%), sleep disturbance (n = 9, 56.3%), and impact on work (n = 9, 56.3%) were the most commonly reported. For CD, the QUALMS and FACT-An were found to be mostly relevant and very well understood; response options were easy to use, and recall period was appropriate.ConclusionBoth QUALMS and FACT-An demonstrated a strong face and content validity in patients with lower-risk MDS, suggesting that these instruments are appropriate for assessing HRQoL in this population.

Health Related Quality of Life and Fatigue in Patients with Pyruvate Kinase Deficiency

Background: Pyruvate Kinase (PK) deficiency is the most common enzyme defect of the glycolytic pathway causing hereditary non-spherocytic hemolytic anemia. Patients have a broad phenotypic spectrum, ranging from mild anemia to transfusion dependence, and there is wide variation in transfusion practices and decisions about splenectomy. No prior studies have reported on the use of validated health related quality of life (HRQoL) measures in this population.Aim: To describe patient reported outcomes including general HRQoL and fatigue in adults with PK deficiency and the correlation with clinical and laboratory features.Methods: Patients were enrolled on the PK Deficiency Natural History Study, a prospective 30 site international study. All patients had molecularly confirmed PK deficiency. Adults (n=132), ages ≥18 years, completed the EuroQol-5D (high index equivalent to better QoL), PROMIS Fatigue Short Form 7a (high scores equivalent to higher fatigue), and the Functional Assessment of Cancer Therapy-Anemia (FACT-An, high scores equivalent to less fatigue) surveys at enrollment and annually. Timing of administration was convenience based. Survey data were analyzed according to proprietary scoring guidelines. Tests of association were performed using Fisher's exact test (categorical) and Wilcoxon rank sum test (continuous). Regular transfusions were defined as ≥6 transfusions in 12 months. Genotypes were grouped as two missense mutations (M/M), one missense/one non-missense (M/NM), or two non-missense mutations (NM/NM)); non-missense included deletions or other drastic variants. The minimal important difference (MID) for the FACT-An has been reported as 7 points (Cella et al, J Pain Symptom Manage 2002). P-values <0.05 were considered statistically significant.Results: At enrollment, 128 adults completed the FACT-An with a median total score of 156 (IQR 122-190). Patients receiving regular transfusions reported significantly lower FACT-An scores than those who were not regularly transfused (median 129 vs 156, p=0.004) with significantly lower scores for physical, emotional, and functional well-being and anemia sub-scores (Table). This difference also surpassed the MID. However, non- regularly transfused patients with hemoglobin (Hb) <8 g/dl did not report significantly different scores than those with Hb≥ 8 g/dl (p=0.75). There were also no significant differences in FACT-An scores by splenectomy status or age. The FACT-An score differences were greater than the MID for patients with iron overload (ferritin >1000 ng/dL or chelation), higher number of lifetime transfusions, and two missense mutations. Females reported significantly lower scores than males (median 143 vs. 160, p=0.006) with significantly lower anemia sub-scores (p=0.0009). FACT-An surveys completed at the one year follow-up time point validated these findings.EuroQol-5D scores (n=124) at enrollment were similar to the healthy population (median PK deficiency index score 0.88; healthy population index mean 0.88, Shaw et al, Medical Care 2005). No significant differences were found by Hb level, splenectomy status, transfusion status, or genotype group. The median PROMIS fatigue T score (n=66) was 52.1 (IQR 40.5-63.7). Similar to the FACT-An survey data, PROMIS fatigue scores were significantly worse in patients who were regularly transfused (67.0 vs 52.4, p=0.02). PROMIS fatigue scores were also significantly worse in patients ≥40 years old (p=0.05) and females (p=0.01).Conclusions: Using the FACT-An and PROMIS Fatigue measures, patients with PK deficiency who are regularly transfused report significantly more fatigue and worse HRQoL compared with those who are not transfused. Important differences were also seen by iron status and mutation group using the FACT-An. Patients report similar fatigue levels regardless of Hb level, which suggests that symptoms, rather than Hb value alone, should be factored into clinical decision making. In contrast to anemia related HRQoL scores, overall HRQoL scores using validated generic measures in patients with PK deficiency show no differences compared with the healthy population, suggesting that disease-specific measures may better detect the effects of PK deficiency on HRQoL. DisclosuresVan Beers:Agios Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Glader:Agios Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Chonat:Agios Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Despotovic:AmGen: Research Funding; Novartis: Research Funding; Sanofi: Consultancy. Kwiatkowski:bluebird bio: Consultancy, Honoraria, Research Funding; Agios Pharmaceuticals: Consultancy, Research Funding; Novartis: Research Funding; Apopharma: Research Funding; Terumo: Research Funding. Thompson:La Jolla Pharmaceutical: Research Funding; Baxalta/Shire: Research Funding; Novartis: Research Funding; Celgene: Research Funding; bluebird bio: Consultancy, Research Funding; Biomarin: Research Funding; Amgen: Research Funding. Newburger:TransCytos LLC: Consultancy; Janssen Research & Development, LLC: Consultancy, Honoraria; X4 Pharmaceutics: Consultancy, Honoraria. Ravindranath:AGIOS: Other: Site Investigator for Pyruvate Kinase Deficiency. Sheth:Terumo Corporation: Research Funding; Novartis: Research Funding; La Jolla Pharmaceutical Company: Research Funding; Celgene Corporation: Consultancy, Research Funding; Bluebird Bio: Consultancy. Grace:Agios Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Research Funding; Agios Pharmaceuticals: Consultancy.

Validation of a patient-reported outcomes symptom measure for patients with nontransfusion-dependent thalassemia (NTDT-PRO© ).

This study demonstrates the quantitative characteristics of the first patient‐reported outcome (PRO) tool developed for patients with nontransfusion‐dependent β‐thalassemia (NTDT), the NTDT‐PRO©. A multicenter validation study was performed over 24 weeks, involving 48 patients from Italy, Lebanon, Greece, and Thailand. Most patients were female (68.8%), with a median age of 34.5 years (range, 18‐52); 66.7% were diagnosed with β‐thalassemia intermedia, and median time since diagnosis was 22 years (range, 0‐43). The NTDT‐PRO comprises 6 items across 2 domains (Tiredness/Weakness and Shortness of Breath [SoB]), and was valid and reliable, with good consistency. At baseline, most patients reported symptoms as present via the NTDT‐PRO, and were highly compliant, ≥90% completing the NTDT‐PRO tool. In a pairwise correlation analysis, all items were positively correlated. Correlations between NTDT‐PRO and existing tools—36‐Item Short Form Health Survey version 2 (SF‐36v2) and Functional Assessment of Cancer Therapy‐Anemia (FACT‐An)—were assessed at weeks 1, 3, and 12; robust correlations were seen between SoB and SF‐36v2‐Vitality (r s = −0.53), and between SoB and Fact‐An‐Fatigue Experience (r s = −0.66) at week 1. Internal consistency was high for both Tiredness/Weakness (Cronbach alpha, 0.91) and SoB (Spearman‐Brown coefficient, 0.78); intraclass correlation coefficients were high (Tiredness/Weakness, 0.88 and 0.97; SoB, 0.92 and 0.98), demonstrating stability. Further studies are required to fully support the validity of this tool, this study demonstrated the usefulness of the NTDT‐PRO in the clinical setting and for longitudinal clinical research, particularly in trials where patient health‐related quality of life is expected to change.

PUK37 - USE OF HEALTH-RELATED QUALITY OF LIFE (HRQOL) INSTRUMENTS IN CLINICAL TRIALS OF ANAEMIA OF CHRONIC KIDNEY DISEASE (CKD)

Anaemia is common in patients with chronic kidney disease (CKD). Symptoms include fatigue, weakness, dyspnoea, dizziness, headaches, pallor, and decreased mental acuity, which could impact on health-related quality of life (HRQoL). This research identifies instruments used to measure HRQoL in anaemia of CKD. A targeted search of PubMed, Embase, and clinicaltrials.gov was performed to identify key phase III clinical trials (defined as those used as evidence in EMA/FDA submissions, HTAs from the EU5/The Netherlands/Sweden, or clinical guidelines) and phase III trials of treatments in development for anaemia of CKD from January 2003 to March 2018. Thirty-four completed key phase III clinical trials were identified, of which nine collected HRQoL data. Thirty-five phase III trials of treatments in development (all hypoxia-inducible factor [HIF] stabilisers) were identified, of which 20 measure HRQoL. Five generic instruments were identified; the most commonly used were the 36-item Short Form (SF-36; seven key trials; 16 trials of HIF stabilisers) and EuroQol Five-Dimensions questionnaires (EQ-5D; 16 trials of HIF stabilisers). Four disease-relevant instruments were used, among them the Functional Assessment of Cancer Therapy-Anaemia (FACT-An; 11 trials of HIF stabilisers) and Kidney Disease Quality of Life questionnaires (KDQOL; two key trials). One disease-specific instrument, the Chronic Kidney Disease-Anaemia Symptoms questionnaire (CKD-AQ), is being used in four trials of HIF stabilisers but is not publicly available for review. The energy and physical activity domains covered in generic instruments may be particularly relevant to the anaemia symptoms of fatigue, weakness, and dyspnoea. The pain and mental/emotional well-being domains are also of potential interest. Symptoms such as headaches, dizziness, and pallor are only captured by disease-relevant instruments. In the absence of a validated anaemia of CKD-specific instrument, a combination of generic and disease-specific instruments for related conditions may allow the most accurate valuation of HRQoL change.

Measurement properties of the Short Form-36 (SF-36) and the Functional Assessment of Cancer Therapy - Anemia (FACT-An) in patients with anemia associated with chronic kidney disease

BackgroundAnemia is a common and debilitating manifestation of chronic kidney disease (CKD). Data from two clinical trials in patients with anemia of CKD were used to assess the measurement properties of the Medical Outcomes Survey Short Form-36 version 2 (hereafter SF-36) and the Functional Assessment of Cancer Therapy-Anemia (FACT-An). The Vitality and Physical functioning domains of the SF-36 and the FACT-An Total, Fatigue and Anemia subscales were identified as domains relevant to CKD-associated anemia.MethodsA total of 204 patients aged 18–80 years were included in the analyses that included internal consistency (Cronbach’s alpha), test-retest reliability (intraclass correlation coefficients [ICCs]), convergent and known-groups validity, responsiveness, and estimates of important change.ResultsBoth the SF-36 and the FACT-An had strong psychometric properties with high internal consistency (Cronbach’s alpha: 0.69–0.93 and 0.79–0.95), and test-retest reliability (ICCs: 0.64–0.83 and 0.72–0.88). Convergent validity, measured by correlation coefficients between similar concepts in SF-36 and FACT-An, ranged from 0.52 to 0.77. Correlations with hemoglobin (Hb) levels were modest at baseline; by Week 9, the correlations with Hb were somewhat higher, r = 0.23 (p < 0.05) for SF-36 Vitality, r = 0.22 (p < 0.05) for FACT-An Total, r = 0.26 (p < 0.001) for FACT-Fatigue and r = 0.22 (p < 0.01) for Anemia. Correlations with Hb at Week 13/17 were r = 0.28 (p < 0.001) for SF-36 Vitality and r = 0.25 (p < 0.05) for Role Physical; FACT-An Total correlation was r = 0.33 (p < 0.0001), Anemia was r = 0.28 (p < 0.001), and Fatigue was r = 0.30 (p < 0.001).The SF-36 domains and Component Summary scores (p < 0.05–p < 0.0001) demonstrated ability to detect change. For the FACT-An, significant differences (p < 0.05–p < 0.0001) were observed between responder and non-responder change scores: important change score estimates ranged from 2 to 4 for Vitality and 2–3 for Physical functioning. Important change scores were also estimated for the FACT-An Total score (6–9), the Anemia (3–5), and Fatigue subscale (2–4).ConclusionsBoth the SF-36 Vitality and Physical function scales and the FACT-An Total, Fatigue and Anemia scales, are reliable and valid measures for assessing health-related quality of life in anemia associated with CKD.

Does access to clinical study reports from the European Medicines Agency reduce reporting biases? A systematic review and meta-analysis of randomized controlled trials on the effect of erythropoiesis-stimulating agents in cancer patients.

Since 2010, the European Medicines Agency (EMA) has provided access to clinical study reports (CSRs). We requested CSRs for randomized controlled trials (RCTs) of erythropoiesis-stimulating agents (ESAs) in cancer patients from EMA and identified RCT publications with literature searches. We assessed CSR availability and completeness, the impact of unreported and unpublished data obtained from CSRs on the effects of ESAs on quality of life (QoL) of cancer patients, and discrepancies between data reported in the public domain and in CSRs. We used random-effects meta-analyses to evaluate the effect of ESAs on QoL measured with Functional Assessment of Cancer Therapy-Anemia (FACT-An), FACT-Fatigue (FACT-F) and FACT-Anemia Total (FACT-An Total) stratified by data source and the impact of discrepancies on QoL, mortality, adverse events, and clinical effectiveness outcomes. We identified 94 eligible RCTs; CSRs or other study documentation were available for 17 (18%) RCTs at EMA. Median report length was 1,825 pages (range 72–14,569). Of 180 outcomes of interest reported in the EMA documentation, 127 (71%) were publicly available. For 80 of those (63%) we noted discrepancies, but these had little impact on the pooled effect estimates. Of 27 QoL outcomes reported in the CSRs, 17 (63%) were unpublished. Including six unpublished comparisons (pooled mean difference [MD] 0.20; 95% confidence interval [CI] -1.93, 2.33) reduced the pooled effect of ESAs for FACT-An from MD 5.51 (95% CI 4.20, 6.82) in published data to MD 3.21 (95% CI 1.38, 5.03), which is below a clinically important difference (defined as MD ≥4). Effects were similar for FACT-F and FACT-An Total. Access to CSRs from EMA reduced reporting biases for QoL outcomes. However, EMA received documentation for a fraction of all RCTs on effects of ESAs in cancer patients. Additional efforts by other agencies and institutions are needed to make CSRs universally available for all RCTs.

A retrospective open-label uncontrolled study of Epoetin zeta on the treatment of chemotherapy-induced anemia in solid tumors.

This is a single-center uncontrolled retrospective study to evaluate the efficacy and safety of the biosimilar epoetin zeta after approval in chemotherapy-induced anemia (CIA). Patients screened were >18years old suffering from solid malignancies and CIA with Hg ≤10 or <11g/dl if symptomatic anemia. Patients had measurable disease by TNM and Eastern Cooperative Oncology Group (ECOG). Patients were treated for at least 12weeks and the primary endpoint was to determine the incidence of blood transfusions, and secondarily, the overall safety and efficacy defined as ≥1g/dl rise in Hb concentration or ≥40,000cells/μl rise in reticulocyte count. Quality of life was assessed with ECOG performance status (PS) and functional assessment of cancer therapy-anemia (FACT-An) score. 1287 patients with median Hb 9.3g/dl (range 8.3-10.6) were enrolled and included in the evaluation. Median age was 63years (range 33-78). 74% of patients were stage III/IV. Patients received epoetin zeta subcutaneously at fixed 40,000-IU once weekly. Blood transfusions were given in 178 patients (13.8%; 95% CI 11.9-15.6%). Appropriate response was observed in 79% patients by week 4, 87% by week 8, and 91% by week 12. A mean Hb increase of 2.5g/dl was observed by week 12 which correlated with an improvement in PS and Fact-An score. Thrombotic events occurred in 5.2% (95% CI 3.4-7.1%) of patients. Epoetin zeta is effective in palliation and treatment of CIA in patients with solid tumors. Overall, it is well tolerated and safe even in patients with increased disease burden.

Ibrutinib for patients with rituximab-refractory Waldenström's macroglobulinaemia (iNNOVATE): an open-label substudy of an international, multicentre, phase 3 trial

In the era of widespread rituximab use for Waldenström's macroglobulinaemia, new treatment options for patients with rituximab-refractory disease are an important clinical need. Ibrutinib has induced durable responses in previously treated patients with Waldenström's macroglobulinaemia. We assessed the efficacy and safety of ibrutinib in a population with rituximab-refractory disease. This multicentre, open-label substudy was done at 19 sites in seven countries in adults aged 18 years and older with confirmed Waldenström's macroglobulinaemia, refractory to rituximab and requiring treatment. Disease refractory to the last rituximab-containing therapy was defined as either relapse less than 12 months since last dose of rituximab or failure to achieve at least a minor response. Key exclusion criteria included: CNS involvement, a stroke or intracranial haemorrhage less than 12 months before enrolment, clinically significant cardiovascular disease, hepatitis B or hepatitis C viral infection, and a known bleeding disorder. Patients received oral ibrutinib 420 mg once daily until progression or unacceptable toxicity. The substudy was not prospectively powered for statistical comparisons, and as such, all the analyses are descriptive in nature. This study objectives were the proportion of patients with an overall response, progression-free survival, overall survival, haematological improvement measured by haemoglobin, time to next treatment, and patient-reported outcomes according to the Functional Assessment of Cancer Therapy-Anemia (FACT-An) and the Euro Qol 5 Dimension Questionnaire (EQ-5D-5L). All analyses were per protocol. The study is registered at ClinicalTrials.gov, number NCT02165397, and follow-up is ongoing but enrolment is complete. Between Aug 18, 2014, and Feb 18, 2015, 31 patients were enrolled. Median age was 67 years (IQR 58-74); 13 (42%) of 31 patients had high-risk disease per the International Prognostic Scoring System Waldenström Macroglobulinaemia, median number of previous therapies was four (IQR 2-6), and all were rituximab-refractory. At a median follow-up of 18·1 months (IQR 17·5-18·9), the proportion of patients with an overall response was 28 [90%] of 31 (22 [71%] of patients had a major response), the estimated 18 month progression-free survival rate was 86% (95% CI 66-94), and the estimated 18 month overall survival rate was 97% (95% CI 79-100). Baseline median haemoglobin of 10·3 g/dL (IQR 9·3-11·7) increased to 11·4 g/dL (10·9-12·4) after 4 weeks of ibrutinib treatment and reached 12·7 g/dL (11·8-13·4) at week 49. A clinically meaningful improvement from baseline in FACT-An score, anaemia subscale score, and the EQ-5D-5L were reported at all post-baseline visits. Time to next treatment will be presented at a later date. Common grade 3 or worse adverse events included neutropenia in four patients (13%), hypertension in three patients (10%), and anaemia, thrombocytopenia, and diarrhoea in two patients each (6%). Serious adverse events occurred in ten patients (32%) and were most often infections. Five (16%) patients discontinued ibrutinib: three due to progression and two due to adverse events, while the remaining 26 [84%] of patients are continuing ibrutinib at the time of this report. The sustained responses and median progression-free survival time, combined with a manageable toxicity profile observed with single-agent ibrutinib indicate that this chemotherapy-free approach is a potential new treatment choice for patients who had heavily pretreated, rituximab-refractory Waldenström's macroglobulinaemia. Pharmacyclics LLC, an AbbVie Company.

Iron Deficiency Anemia Coexists with Cancer Related Anemia and Adversely Impacts Quality of Life.

Cancer related anemia (CRA) adversely affects patient Quality of Life (QoL) and overall survival. We prospectively studied the prevalence, etiology and the impact of anemia on QoL in 218 Indian cancer patients attending a tertiary referral hospital. The study used the sTfR/log Ferritin index to detect iron deficiency anemia and assessed patient QoL using the Functional Assessment of Cancer Therapy-Anemia (FACT-An) tool, standardized for language. Mean patient age was 51±13 years and 60% were female. The prevalence of cancer related anemia in this setting was 64% (n = 139). As expected, plasma ferritin did not differ significantly between anemic (n = 121) and non-anemic cancer patients (n = 73). In contrast, plasma sTfR levels were significantly higher in anemic cancer patients compared to non-anemic cancer patients (31 nmol/L vs. 24 nmol/L, p = 0.002). Among anemic cancer patients, using the sTfR/log Ferritin index, we found that 60% (n = 83) had iron deficiency anemia (IDA). Interestingly, plasma sTfR levels were significantly higher in cancer patients with CRA+IDA (n = 83) compared with patients having CRA (n = 38) alone (39 nmol/L vs. 20 nmol/L, p<0.001). There was a significant linear correlation between Hb and QoL (Spearman ρ = 0.21; p = 0.001) and multivariate regression analysis revealed that every gram rise in Hb was accompanied by a 3.1 unit increase in the QoL score (95% CI = 0.19–5.33; p = 0.003). The high prevalence of anemia in cancer patients, a major portion of which is due to iron deficiency anemia, the availability of sensitive and specific biomarkers of iron status to detect IDA superimposed on anemia of inflammation, suggests an urgent need to diagnose and treat such patients. Despite the potential negative consequences of increasing metabolically available plasma iron in cancer, our clinical data suggest that detecting and treating IDA in anemic cancer patients will have important consequences to their QoL and overall survival. Clinical trials of iron therapy in these patients will be able to demonstrate the potential for benefit or harm.

Impact of resistance and aerobic exercise on sarcopenia and dynapenia in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial.

The purpose of this study was to conduct an exploratory analysis of the START examining the effects of resistance exercise training (RET) and aerobic exercise training (AET) on sarcopenia, dynapenia, and associated quality of life (QoL) changes in breast cancer (BC) patients receiving adjuvant chemotherapy. Participants were randomized to usual care (UC) (n=70), AET (n=64), or RET (n=66) for the duration of chemotherapy. Measures of sarcopenia [skeletal muscle index (SMI)] and dynapenia [upper extremity (UE) and lower extremity (LE) muscle dysfunction (MD)] were normalized relative to age-/sex-based clinical cut-points. QoL was assessed by the Functional Assessment of Cancer Therapy-Anemia (FACT-An) scales. At baseline, 25.5% of BC patients were sarcopenic and 54.5% were dynapenic with both conditions associated with poorer QoL. ANCOVAs showed significant differences favoring RET over UC for SMI (0.32kg/m(2); p=0.017), UE-MD (0.12kg/kg; p<0.001), and LE-MD (0.27kg/kg; p<0.001). Chi-square analyses revealed significant effects of RET, compared to UC/AET combined, on reversing sarcopenia (p=0.039) and dynapenia (p=0.019). The reversal of sarcopenia was associated with clinically relevant improvements in the FACT-An (11.7 points [95% confidence interval (CI) -4.2 to 27.6]), the Trial Outcome Index-Anemia (10.0 points [95% CI -4.0 to 24.1]), and fatigue (5.3 points [95% CI -1.5 to 12.1]). Early-stage BC patients initiating adjuvant chemotherapy have higher than expected rates of sarcopenia and dynapenia which are associated with poorer QoL. RET during adjuvant chemotherapy resulted in the reversal of both sarcopenia and dynapenia; however, only the reversal of sarcopenia was associated with clinically meaningful improvements in QoL.

Fatigue, Quality of Life and Related Symptoms: Patient Reported Outcomes in Myelodysplastic Syndrome, Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria

Background: Fatigue is common and very distressing among patients with myelodysplastic syndrome (MDS), aplastic anemia (AA), and paroxysmal nocturnal hemoglobinuria (PNH), frequently affecting their quality of life. Often, this is combined with other symptoms such as pain, depression, anxiety, and stress. Limited data exists on the perceived level and impact of fatigue, quality of life and related symptoms in these patients.The objectives are to describe fatigue, quality of life (QOL) and related symptoms in patients with MDS, AA, and PNH by prospectively assessing these using the Functional Assessment of Cancer Therapy-Anemia (FACT-An) for fatigue and QOL (subscales within FACT- An), pain using the Brief Pain Inventory (BPI), and depression, anxiety and stress using the DASS-21, and to define management strategies routinely used.Methods: Surveys were administered via the AA and MDS International Foundation's patient database from 10/2014 through 1/2015 via a secure internet portal associated with the Foundation's website. Descriptive statistics were utilized.Results: Of 313 pts, 145 (46%) had MDS, 84 (27%) had AA, 74 (24%) PNH, and 10 (3%) unreported [31 (10%), >1 diagnosis]. The mean age was 57 years with 210 (67%) female, 197 (92%) white among 214 with known race and 70 (25%) received a blood transfusion in the past 90 days. The mean fatigue score overall was 25 (range 1-52) and 28, 25, and 24 for AA, MDS, and PNH, respectively, p=0.12. (severe level). The overall quality of life score was 68 (range 10-104) and 67, 69, 67 for AA, MDS, PNH, respectively, p=0.82. Please note with the FACT-An, FACT-G and FACT-F -The higher the score, the better the QOL. The overall ranges for stress were normal; pain and depression, mild; and anxiety, moderate. Among the subgroups, stress was normal (all); pain and depression were mild (all); anxiety was mild in MDS, moderate in AA, PNH. None of the subgroups had statistical significance for these symptoms including anxiety.Most common management strategies used for fatigue in the past month were preserving energy 252 (81%); physical activity 234 (75%); naps 228 (73%). The strategies that were helpful to extremely helpful were preserving energy 216/252 (86%), physical activity 162/234 (69%), and naps 154/228 (68%). Among subgroups, physical activity (p=0.03) and meditation (p=0.03) showed significant differences. Frequency of use 3 or more times/week were preserving energy 166/237 (70%), physical activity 128/226 (57%), and naps 131/213 (62%) among those who indicated the frequency of use. Among subgroups, the frequency of physical activity p= 0.03, eating healthy p=0.005, and counseling p=.005 showed significant differences.Conclusions: There are few patient reported outcomes of fatigue, QOL and related symptoms in this population of rare disorders. Fatigue and QOL are significant challenges with similar findings of fatigue, QOL and related symptoms among the subgroups. However, there were differences among the types of management strategies and the frequency of use among the subgroups. Further focus on development of interventions tailored for AA, MDS, and PNH may assist in better management of fatigue with potential improvement in QOL. DisclosuresNo relevant conflicts of interest to declare.

Quality of Life in Low-Risk Myelodysplastic Syndrome: A Cross-Sectional Study

Myelodysplastic syndrome (MDS) is mainly a disease of elderly population. Chronic cytopenias, especially anemia, frailty comorbidities, and age may alter the physical status significantly. Only a few proportions of patients can achieve long-term cure. In particular, but not limited to patients with low risk MDS; palliative/supportive care is the mainstay of the treatment. Erythropoietin-stimulating agents (ESAs) and red blood cell transfusions are the treatment options for patients suffering from anemia. Except one study, ESA-responders had a better quality of life (QoL) in three studies. Hematologic improvements should be assesses by patient-reported outcomes (PROs) as well as objective measures. Validated PROs those were used to assess QOL in patients with MDS included Functional Assessment of Cancer Therapy- Anemia (FACT-An) and European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC-QLQ C30) questionnaires and a MDS-specific questionnaire, QoL-E.All patients with MDS were screened. Patients with low-risk MDS were included in the study. One physician completed FACT-An, Hematopoietic Stem Cell Transplantation-Comorbidity Index (HCT-CI), and G8 frailty questionnaires in all patients. Demographic data were collected from patients' chart records.A total of 66 patients were screened. Fourteen patients were excluded due to high-risk MDS or indefinite diagnosis. In one patient, informed consent could not be obtained. Finally, 51 patients were included in the study. Median age was 66 years old (interquartile range [IQR]: 55-77). Twenty-one out of 51 patients (41.2%) were male. Most prevalent MDS subtype was MDS-refractory anemia (47%). All patients had very-low/low (86.3%) or intermediate-risk (13.7%) MDS according to age-adjusted IPSS-R (IPSS-RA). Median time from the diagnosis of MDS was 113 (IQR: 53-170) weeks. Twenty-eight patients (54.9%) were transfusion-dependent. Ten patients had a high transfusion burden, which was defined as transfusion requirement ≥4 units (U) over 8 weeks. Median transfusion duration was 112 (IQR: 31-173) weeks for transfusion-dependent patients. Median red blood cell transfusion during eight weeks was 1.5 (IQR: 0-4.5) U. Median hemoglobin concentration was 10.0 (7.9-11.3) g/dL for all patients. A total of nineteen patients (37.3%) were ESA-user/responder. Most of the patients (80.4%) had a low (<11 years) education level. Thirty-eight (74.5%) patients were living with their parents or partners. A half of the patients had an ECOG performance status ≤2. Sixty per cent were frail and 39% had significant (≥2) comorbidities.In univariate analyses, older age (β: -0.740, 95% CI: -1.138; -0.341, p<0.001), higher transfusion burden (β: -7.235, 95% CI: -14.279; -0.190, p=0.044), intermediate risk IPSS-RA (β: -8.113, 95% CI: -15.715; -0.511, p=0.037), lower educational status (β: -19.625, 95% CI: -32.565; -6.684, p=0.004), lower ECOG performance status (≥2) (β: -14.385, 95% CI: -24.805; -3.964, p=0.008), frailty (β: -13.740, 95% CI: -24.518; -2.962, p=0.014), and being ESA-user/responder (β: -15.431, 95% CI: -26.141; -4.722, p=0.006) were associated with worse FACT-An total scores.Multivariate analyses revealed that age (β: -0.738, %95 GA: -1.101; -0.374, p<0.001) and being ESA-user/responder (β: 15.368, %95 GA: 6.040; 24.697, p=0.002) were the only independent predictors of QoL in patients with low-risk MDS (Table 1, figure 1).Model stability was tested in 5000 bootstrap replicates of dataset. Age and being ESA-user/responder were included in 40.6% and 38.2% of all models (Table 1).These data indicates that age and ESA use are independent parameters of QoL in low-risk MDS. Impact of ESA use on QoL is independent from the hemoglobin level. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.