Cross-Sectional Survey of Symptoms and Health-Related Quality of Life of Adults with De Novo Acute Myeloid Leukemia (AML) in Clinical Practice

Introduction: The care of adults with acute myeloid leukemia (AML) is complex, involving repeated courses of chemotherapy; many patients suffer from sequelae of cytopenias and treatment-related toxicities that impair their health-related quality of life (HRQoL). Because knowledge regarding symptom burden and HRQoL is largely derived from academic centers' experience, there are uncertainties regarding how this compares to the real-world experience.

Methods: The Adelphi AML Disease-Specific Program (DSP), a real-world, cross-sectional survey, was conducted in the US between February-May 2015; 61 hematologist/oncologists completed patient record forms for the next 6-8 adult patients with primary (de novo) AML with whom they consulted. Physicians reported demographics, clinical background, and treatment history for each patient. Patients were invited to complete the Functional Assessment of Cancer Therapy Leukemia (FACT-Leu) and EuroQoL 5 Dimensions (EQ-5D) questionnaires, which assess patient HRQoL and functional health status, respectively. Patients were categorized as newly diagnosed (NEW: currently on 1^st line AML treatment), relapsed/refractory (RR: currently on 2^nd line or later AML treatment), or not currently receiving active AML treatment (NO). Analysis of variance was used for quantitative outcomes, while chi-square and Fisher's exact tests were used for categorical outcomes, to determine statistical differences between patient groups. Effect sizes were calculated using Cohen's d. Minimally important differences (MIDs), required to suggest clinical importance on FACT-Leu and EQ-5D, were also examined.

Results: Physician-completed data on 415 patients (median age: 61 years, 55% male) were obtained (NEW: 82%; RR: 12%; NO: 6%). At the time of most recent consultation, 46% of patients were currently in full or part-time employment, 31% required some caregiver support and 27% were considered asymptomatic. Among those who experienced symptoms, fatigue (24%), bruising (10%), loss of appetite (10%), and nausea (9%) were most common.

When comparing subgroups, 58% of NO patients and 66% of RR patients were still in full or part-time employment compared with 42% of NEW patients; however, RR and NO patients were more likely than NEW patients to require some degree of caregiver support (RR: 48%, NO: 50%, NEW: 27%). The current symptom most commonly reported was fatigue (23% NEW, 32% RR, and 15% NO).

Seventy-five patients (median age: 60 years, 53% male) provided self-reported information (68% NEW, 23% RR, and 9% NO). Results from the FACT-Leu indicated that physical well-being (PWB), leukemia-related well-being (LRW), well-being as measured by the Trial Outcome Index (TOI), and FACT-Leu Total Score were significantly affected by stage of treatment (PWB: p<0.001, LRW: p=0.002, TOI: p=0.011; Total: p=0.035), with NO patients consistently scoring lowest in all domains. Large differences in mean domain scores, exceeding the MIDs, were observed across the patient subgroups for the FACT-Leu. Large effect sizes were seen between NEW and NO patients for PWB (d=1.27 standard deviation units), LRW (d=1.35), and the TOI (d=1.02). Between RR and NO patients, large effect sizes were seen for functional well-being (FWB: d=0.80), and LRW (d=0.95). Between NEW and RR patients, a large effect was seen for PWB (d=0.83) and a moderate effect for TOI (d=0.54). In general, differences between NEW and RR patients were small to moderate, suggesting HRQoL was similar for the two patient populations, and differences between the NEW and NO group were moderate to large.

Results from the EQ5D did not show a significant difference in the utility score between NEW (M=0.74), RR (M=0.73) and NO (M=0.76) patients. The effect sizes for any differences in EQ5D utility score were also small, whereas the difference between NO and RR patients for the EQ5D Visual Analogue Scale was moderate (d=0.57).

Conclusions: In this novel real-world analysis of AML patients, differences in symptomatology, level of caregiver involvement, and HRQoL were observed across NEW, RR, and NO patients. Regarding HRQoL, the disease-specific FACT-Leu appears more sensitive than the EQ-5D, indicating that NEW patients overall fare better than RR patients, who fare better than NO patients. These results suggest effective and tolerable treatments that delay progression of the disease are important to conserve patients' HRQoL.