Association of Financial Toxicity and Health-Related Quality of Life in Long-Term Survivors of Acute Promyelocytic Leukemia Treated within a Universal Healthcare System
Authors: Sparano Francesco , Venditti Adriano , Voso Maria Teresa , Giesinger Johannes M. , Brini Alberto , Fazi Paola , Vignetti Marco , Efficace Fabio 
Published: December 2023

Background
Financial toxicity (FT) indicates the harmful consequences of cancer-related costs on patients' clinical outcomes and health-related quality of life (HRQoL). Although literature on this subject in patients with solid tumors is growing, little is known on patients with hematologic malignancies treated within a universal healthcare system. For example, despite being cured of their disease, long-term survivors of acute promyelocytic leukemia (APL) may still report health status problems which may be associated with financial constraints.
Aims
Our primary objective was to investigate the prevalence of clinically important problems and symptoms in survivors of APL with or without FT treated within a universal healthcare system. A secondary objective was to examine potential risk factors associated with FT.
Methods
We did a cross-sectional analysis of two multicenter studies conducted by the GIMEMA Group that enrolled long-term survivors of APL treated with either standard chemotherapy or arsenic trioxide (ATO). FT was evaluated using the financial difficulties item of the EORTC QLQ-C30 questionnaire. Patients treated in Italian centers were selected and classified as experiencing or not FT based on evidence-based thresholds for defining clinically important problems and symptoms of the QLQ-C30, established to help to improve the interpretation of this questionnaire in clinical practice. Using the same criteria, we assessed the prevalence of clinically important problems and symptoms at the patient level, in the groups of survivors of APL with or without FT. Multivariable binary logistic regression analysis was performed to examine potential risk factors associated with FT. The following covariates were considered: sex (female vs male), age at study entry, time since diagnosis, living arrangements (living alone vs living with others), receiving a salary/pension (no vs yes), level of education (high education level vs middle-low level), comorbidities (≥1 vs 0), and type of treatment received (chemotherapy vs ATO). All statistical tests were two-sided with a nominal α=0.05, and there was no adjustment for multiple testing due to the exploratory nature of the study.
Results
Overall, 365 survivors of APL were analyzed and 23.8% of them reported FT. Most patients (n=304, 83.3%) were treated with chemotherapy and 61 (16.7%) with ATO. Median age at study entry was 53.5 years (IQR: 43.9 - 63.0) and median time since diagnosis was 10.9 years (IQR: 7.9 - 15.7). More than half of survivors of APL were female (n=192; 52.6%), and 68 (18.9%) were living alone. The following characteristics were well-balanced between patients with and without FT: treatment, age, time since diagnosis, living arrangements, and sex. Some one-third of survivors (n=113, 31.4%) was not receiving a salary/pension, and this prevalence was higher among survivors with FT than those without FT (41.9% vs 28.1%). Prevalence of comorbidities was also higher among survivors with FT versus those without FT (87.4% vs 74.5%).
The prevalence of clinically important problems and symptoms was statistically significant higher for survivors of APL who reported FT across all scales of the QLQ-C30, except for appetite loss and constipation (Figure 1). For example, with regard to the functioning scales the prevalence of clinically important emotional functioning problems was 50.6% and 19.8% in the group of survivors with and without FT, respectively. The prevalence of clinically important cognitive functioning problems was 41.4% for survivors with FT vs 16.9% in those without FT. The trend for symptom burden was similar, for example the prevalence of clinically important dyspnea was 51.7% and 25.3% in the group of survivors with and without FT, respectively. In the multivariable analysis, the presence of FT was independently associated with having at least one comorbidity (OR 2.44; p = .012), and not receiving a salary/pension (OR 1.90; p = .014).
Conclusions
Despite being treated within a universal healthcare system and being cured of their disease, some one-fourth of survivors of APL experience FT and these patients report a higher prevalence of clinically important problems and symptoms compared to those without FT. Considering the expected growing population of survivors, owing to the remarkable APL treatment advances, efforts to mitigate FT may be critical to improve long-term HRQoL outcomes.