BackgroundBarth syndrome (BTHS, OMIM 302060) is a rare, life-threatening, x-linked genetic disorder that occurs almost exclusively in males and is characterized by cardiomyopathy, neutropenia, skeletal muscle myopathy primarily affecting larger muscles, and shorter stature in youth. A greater number of individuals with BTHS are now surviving into adulthood due to advancements in diagnosis and disease management. Given these improvements in life expectancy, understanding the disease experience over time has become increasingly important to individuals with the condition, treatment developers, and regulatory agencies. A study was conducted to explore the experience of BTHS from the perspective of adult males at least 35 years of age with the condition via in-depth qualitative interviews.ResultsFindings showed that adults with BTHS experienced a variety of signs/symptoms with variable onset and severity throughout their lives, the most frequently reported being the symptoms of tiredness, muscle weakness, and a fast and/or irregular heart rate, and the sign of short stature in youth. These signs/symptoms negatively impacted individuals’ emotional, physical, social, and role functioning. Tiredness and weakness impacted some individuals’ physical functioning from an early age and into adulthood. These symptoms generally worsened over time, increasingly interfering with individuals’ ability to fully participate in paid and unpaid labor and to partake in family and leisure activities.ConclusionsThis research complements recent studies characterizing the potentially degenerative and progressive nature of BTHS and can encourage future research into the natural history and progression of BTHS in untreated individuals. Participants’ interview responses revealed a range of symptoms and the potential for multiple impacts on individuals’ physical, social, emotional, and role functioning as a result of BTHS symptoms, yet also revealed variability in severity of experience as well as the possibility of resilience and adaptation to the condition.
Introduction: Novel therapies for relapsed/refractory multiple myeloma (RRMM) have demonstrated durable responses that prolong survival, thus assessing health-related quality of life (HRQoL) is becoming increasingly important in patient (pt) care. Long-term RRMM treatment may lead to a higher cumulative symptom burden and negatively affect HRQoL. Indeed, the effect of treatment on HRQoL is reduced in pts with RRMM on later vs initial lines of therapy (LoTs) (Nielsen et al, Eur J Hematol 2017). Consequently, there is a need for treatments that demonstrate durable efficacy while preserving HRQoL. Pomalidomide plus dexamethasone (Pd) has been shown to be an effective treatment for RRMM that does not negatively affect HRQoL in later LoTs (Song et al, Haematologica 2015). In the randomized phase 2 ELOQUENT-3 study (NCT02654132), addition of the SLAMF7-targeted monoclonal antibody elotuzumab (elo) to Pd (EPd) showed a 46% reduction in the risk of progression/death vs Pd, and acceptable safety in pts with refractory or relapsed and refractory MM for whom therapy with lenalidomide and a proteasome inhibitor had failed (Dimopoulos et al, EHA 2018 [LB2606]). We present pt-reported outcome (PRO) data to assess the impact of EPd on HRQoL in pts from ELOQUENT-3. Methods: The M.D. Anderson Symptom Inventory MM module (MDASI-MM) and the 3-level version of the EuroQoL 5 Dimensions Questionnaire (EQ-5D-3L), which included the global health visual analog scale (VAS) measure, were administered at baseline (BL) and at the start of every 28-day treatment cycle until discontinuation and at survival follow-up. All randomized pts with BL and ≥1 post-BL assessment were included in the PRO analysis. Changes from BL scores were evaluated descriptively: high scores indicate better health for EQ-5D-3L, but more severe symptoms for MDASI-MM. Time to first deterioration was evaluated, with a deterioration event defined as the absolute value of the change from BL ≥ the responder definition threshold (MDASI-MM symptom item assessing pain, fatigue, and bone aches: 2; EQ-5D-3L VAS: 7). Results: This analysis included 117 randomized pts (EPd, n=60; Pd, n=57) who had received a median of 3 prior LoTs. PRO completion rates at BL were 79% for MDASI-MM (EPd, 85%; Pd, 72%) and 84% for EQ-5D-3L (EPd, 88%; Pd, 79%). Although completion rates between treatment groups were similar throughout the study, analysis of QoL was not feasible after Cycles 13 for EPd and 10 for Pd as the number of pts with questionnaires dropped below 20%. Mean BL QoL scores were similar for EPd vs Pd (EQ-5D-3L utility, 0.676 vs 0.682; EQ-5D-3L VAS global health status, 61.9 vs 62.9). A clinically meaningful deterioration from BL in EQ-5D-3L VAS health status (mean change -9.0) was observed with Pd at Cycle 2. In contrast, there were no clinically relevant deteriorations in EQ-5D-3L VAS health status with EPd, and a sustained improvement from BL was observed between Cycles 9 and 12 (mean change 8.2, 11.7, 9.7, and 10.4, respectively; Figure). MDASI-MM symptom scores for pain and bone aches showed no clinically relevant change from BL levels in both groups, but fatigue worsened (mean change 2.5) in the Pd group at Cycle 9. Pts who discontinued treatment early tended to have lower HRQoL in both treatment arms. There were no differences in time to first deterioration for EPd vs Pd for MDASI-MM symptoms pain, fatigue, or bone aches, or EQ-5D-3L and VAS domains. Although the risk of deterioration in the severity of MDASI-MM core symptoms (symptoms common across cancer types and treatments) was reduced by 17% (hazard ratio 0.83; 95% CI 0.49-1.42) for those receiving EPd vs Pd, this was not statistically significant (p=0.618); the median time to deterioration was 3.8 mo with EPd and 1.2 mo with Pd. Conclusions: In ELOQUENT-3, pt-reported health status was maintained in pts who remained on EPd per EQ-5D-3L VAS, with no worsening of pain, fatigue, or bone aches per MDASI-MM. There were minimal differences in QoL between pts who received EPd and Pd, suggesting that the addition of elo to Pd does not impair HRQoL, although HRQoL may have been overestimated due to the small sample and treatment discontinuation. These pt-reported findings complement strong clinical data that demonstrated clinically relevant improvements in efficacy and a favorable safety profile for EPd, further supporting the use of this regimen in RRMM. Study support: BMS. Writing support: Simon Wigfield, Caudex, funded by BMS. Figure. Figure. Disclosures Weisel: Amgen, BMS, Celgene, Janssen, and Takeda: Honoraria; Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen, Celgene, Janssen, and Sanofi: Research Funding. Paner:Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria. Taylor:Adelphi Values: Employment; Bristol-Myers Squibb: Consultancy. Cocks:Adelphi Values: Employment; Amgen: Consultancy; Bristol-Myers Squibb: Consultancy; Celgene: Consultancy; Endomag Ltd.: Consultancy. Espensen:Adelphi Values: Employment; Bristol-Myers Squibb: Consultancy, Other: I am an employee of Adelphi Values, a consulting firm that has received payment from BMS for statistical data analysis in BMS trials. Popa-McKiver:Bristol-Myers Squibb: Employment. Chen:Bristol-Myers Squibb: Employment. Cavo:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees.
Objectives: Primary mitochondrial myopathy (PMM) is a genetic condition characterized by life-limiting symptoms such as muscle weakness, fatigue, and pain. Because these symptoms are best reported by individuals with PMM, the objective of this qualitative research study was to develop a PMM-specific patient-reported outcome (PRO) questionnaire. Method: Individuals with PMM were interviewed, identifying the most salient symptoms of PMM and assessing the resulting questionnaire's relevance and comprehensibility. Results: Developed based on patient interviews, the 10-item Primary Mitochondrial Myopathy Symptom Assessment assesses patients' symptom experiences at their worst in the last 24 hours. Individuals with PMM confirmed the concepts of the questionnaire as relevant and comprehensive to their symptom experiences and responded to the items consistently with developers' intentions. Conclusions: The Primary Mitochondrial Myopathy Symptom Assessment is a content-valid PRO questionnaire with qualitative and quantitative support as a valuable tool to evaluate and monitor the day-to-day experience of PMM symptoms from the patient perspective.
items on self-consciousness and embarrassment into 40 languages for 50 countries across three translation projects (for 72 total translations). The harmonized questionnaires underwent in-person cognitive interviews with atopic dermatitis and head & neck cancer patients. We extracted patient demographic and item comprehension information, as well as feedback regarding comprehension problems, from 356 interviews. RESULTS: Patients (n ¼ 356) were aged 11-95 years, with length of education from 0-20 years (mean ¼ 11.9). Comprehension problems with self-conscious and embarrassed were noted in 12 / 39 languages (31%), 14 / 50 countries (28%), 17 / 72 translations (24%), and accounted for 55% of the total number of comprehension errors across all debriefing sessions. Patients reported that self-conscious and embarrassed were difficult to separate conceptually, and suggested that only one of the concepts was necessary. Patients also had difficulty comprehending / paraphrasing self-conscious itself, and were frequently unable to provide alternative translations. CONCLUSIONS: Patients demonstrated considerable difficulty interpreting the terms self-conscious and embarrassed in three PROs. We attribute this to their semantic overlap and co-occurrence in contexts where they are intended to assess different constructs. We recommend greater effort to differentiate self-conscious and embarrassed in PROs containing both in order to improve comprehensibility and translations of both terms.
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