Health-Related Quality of Life with Gilteritinib Versus Placebo Post-Transplant Maintenance for FLT3-ITD+ Acute Myeloid Leukemia (AML): A Quality of Life Analysis from BMT CTN 1506

The Blood and Marrow Transplant Clinical Trials Network study 1506 (NCT02997202) was a multi-center phase III randomized trial comparing gilteritinib versus placebo after allogeneic hematopoietic cell transplantation (HCT) in patients with FLT3-ITD-positive AML. The primary analysis comparing relapse-free survival (RFS) did not reach statistical significance, with higher treatment-emergent adverse events (TEAE) with gilteritinib. In patients with detectable FLT3-ITD measurable residual disease (MRD) peri-HCT, gilteritinib was associated with significantly longer RFS, demonstrating efficacy of MRD monitoring and intervention with FLT3 inhibition in MRD positive patients. The impact of gilteritinib maintenance on health-related quality of life (HRQoL) is not known; and the aim of this prespecified exploratory analysis is to describe the effect of gilteritinib versus placebo on HRQoL.HRQoL was measured using the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), FACT-Leukemia (-Leu), and EQ-5D-5L at post-HCT randomization (baseline), day 29, month 3, 6, 12, 18, 24, and/or end of therapy. FACT assesses physical, social, emotional, functional domains, and specific BMT and Leu concerns, respectively. EQ-5D measures mobility, self-care, activity, pain, and anxiety/depression. Higher scores indicate higher HRQoL. HRQoL and clinically meaningful differences were summarized using descriptive statistics and compared between arms using mixed model repeated measures to evaluate longitudinal change from baseline.Between 8/2017 and 7/2020, 356 patients were randomized, 178 to each arm. HRQoL completion rate among patients alive and on treatment was acceptable (>70%) across all time points and measures. There were no significant differences in FACT-BMT, FACT-Leu, or EQ-5D-5L scores at any time point between cohorts; however, there was an increase in scores over time, indicating improvement in HRQoL post-HCT regardless of treatment. Clinically meaningful improvement as measured by change from baseline scores and time to improvement in HRQoL scores was also similar in both arms (Table, Figure 1). Despite a higher incidence of TEAEs in the gilteritinib arm compared to placebo, similar results were observed for an individual FACT question assessing if patients were “bothered by side effects of treatment” between groups. The proportion of patients reporting “not at all” increased over time for both treatment arms. (Figure 2). Subgroup analysis of MRD positive and negative patients demonstrated no differences in HRQoL between arms across 24 months for any scores.HRQoL measurement in clinical trials is critical to the assessment of treatment benefit or risk from the patients’ perspective. For patients with FLT3-ITD+ AML, compared to placebo, gilteritinib maintenance was not associated with any difference in HRQoL or patient-reported tolerability.