OBJECTIVES: Previous patient-reported outcome analyses in the phase 3 ADMIRAL study have provided an understanding of disease-related symptoms and health-related quality of life in FLT3-mutated relapsed or refractory acute myeloid leukemia (FLT3^mut+ R/R AML). The objective of this analysis was to validate the Brief Fatigue Inventory (BFI), Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu), and Functional Assessment of Chronic Illness Therapy-Dyspnea Short Form (FACIT-Dys-SF) instruments in FLT3^mut+ R/R AML, using data from ADMIRAL.

METHODS: Analyses were performed using pooled baseline data from gilteritinib and chemotherapy arms. Individual item and domain characteristics were summarized by descriptive statistics, and floor and ceiling effects were examined. Reliability was assessed by Spearman rank correlations (r_s) and Cronbach’s alpha (α) coefficient. Construct validity was evaluated by examining known-group validity (by Eastern Cooperative Oncology Group [ECOG] performance status, cytogenetic risk, and prior transplant status) and convergent validity (Spearman rank correlation coefficients). Clinically meaningful differences were calculated for BFI scores using distribution- and anchor-based approaches.

RESULTS: Patients’ responses covered the full range of each item for all instruments, although all three showed some degree of ceiling effect. Moderate-to-strong correlations between all items within their subscale (r_s≥0.3) were found without signs of redundancy. Moderate-to-high correlations for most items and corresponding scales (r_s≥0.4) were observed; all instruments showed acceptable internal consistency (α>0.7). All instruments differentiated groups of patients by ECOG performance status at baseline, but not by cytogenetic risk or prior transplant status. Convergent validity was achieved with all instruments. Thresholds for clinically meaningful deterioration in BFI were 1-4 points, with the lowest thresholds obtained using the distribution-based method (1.27-1.32).

CONCLUSIONS: In patients with FLT3^mut+ R/R AML in the phase 3 ADMIRAL study, the BFI, FACT-Leu, and FACIT-Dys-SF showed good psychometric properties, although ceiling effects may limit the ability to detect treatment effects when high-functioning patients are enrolled at baseline.