Profiling Baseline Health-Related Quality of Life of Patients with Newly Diagnosed Myeloid Malignancies: A Pooled Analysis of 3349 Patients with AML, APL and MDS from the International Proactive Project
Authors: Efficace Fabio , Venditti Adriano , Baldi Thomas , Canham Joanna , Martinelli Giovanni , Piciocchi Alfonso , Dennis Mike , Knapper Steve , Russell Nigel H. , Johnson Sean , Voso Maria Teresa , Vignetti Marco , Thomas Ian 
Published: December 2024

Background
Notable advances have been made in the treatment of patients with myeloid malignancies in recent years, thereby making health-related quality of life (HRQoL) a critical aspect to consider. However, limited data exists on the HRQoL and symptom burden profile of these patients.
Objective
The main objective of this study was to assess the prevalence of clinically important symptoms in a large cohort of newly diagnosed patients with AML, APL and MDS. A secondary objective was to investigate differences in the baseline HRQoL profile across these diseases.
Methods:
Data were gathered through the PROACTIVE project, a large international initiative aimed at enhancing evidence-based knowledge on patient-reported outcomes (PRO) in patients with AML/MDS. To this end, a number of high-quality datasets (including at least the EORTC QLQ-C30) from international cooperative groups are being pulled together. For the purpose of this study, a sample of 2370 patients from NCRI-UK trials and 1551 newly diagnosed patients from GIMEMA studies were combined, resulting in a final sample of 3921 patients. Only patients with valid baseline (pretreatment) HRQoL questionnaires were considered for this analysis (n=3349/3921, 85%). A total of 2046 (61%) patients were diagnosed with AML with a median age of 69 years, 1078 (32%) diagnosed with MDS, with a median age of 73 years; the remaining 225 patients (7%) were diagnosed with APL with a median age of 46 years. The prevalence of clinically important symptoms in the overall population and by disease group was based on previously established thresholds for the EORTC QLQ-C30 (Giesinger JM, et al.J Clin Epidemiol. 2020 Feb;118:1-8). A higher score for a functional scale represents a higher level of functioning while a high score for a symptom scale represents a higher level of symptomatology. Multivariable linear regression models were used to assess cross-sectional mean differences between types of diagnosis for the EORTC QLQ-C30 scales. Given the higher prevalence of patients with AML, we used this as a reference category for each regression model adjusted for sex and age. The magnitude of clinical relevance (small, medium and large) of the adjusted mean differences was evaluated using established scale-specific thresholds.
Results
Analysis of baseline symptom prevalence in the overall population indicated a substantial burden of the disease with the 5 most prevalent clinically important symptoms being: dyspnea (69%), nausea/vomiting (58%), pain (48%), fatigue (40%) and appetite loss (24%).
No statistically significant difference was observed in the prevalence of fatigue across AML, APL and MDS patients. However, the prevalence of other symptoms varied by disease, with APL patients typically reporting higher prevalence followed by AML and MDS. For example, nausea/vomiting was 89%, 70% and 30% (p&lt;.001) for APL, AML and MDS respectively. Also, pain was 60%, 53% and 34% (p&lt;.001) for APL, AML and MDS respectively.
Investigation of the baseline HRQoL profile revealed differences across diseases. Relative to patients with AML, those with APL had worse large clinically relevant differences for cognitive functioning (∆ = -23.7), nausea/vomiting (∆ = 24.8), and dyspnea (∆ = 17.5). APL patients also had worse medium to small clinically relevant differences for appetite loss (∆ = 14.3), role functioning (∆ = -9.9), constipation (∆ = 9.7), pain (∆ = 9.4), diarrhea (∆ = 7.9), physical functioning (∆ = -6.0), insomnia (∆ = 5.1) and global QoL (∆ = -4.4). Relative to patients with AML, those with MDS reported large better clinically relevant differences regarding dyspnea (∆ = -18.3) and nausea/vomiting (∆ = -25.5). MDS patients also had medium to small better clinically relevant differences for cognitive functioning (∆ = 11.9), global QoL (∆ = 6.2) as well as appetite loss (∆ = -13.3) and pain (∆ = -12.8).
Conclusion:
Our findings indicate that patients with AML, APL and MDS experience a high symptom burden already at the time of diagnosis. Current data also helps to characterize the specific baseline HRQoL profile of these patients highlighting most relevant functional aspects and symptoms in need of special attention for each disease. Future analyses are planned to investigate longitudinal trajectories of HRQoL by type of treatment and other key characteristics