A randomized, open-label, phase 3 trial (NCT02752035) compared the efficacy and safety/tolerability of the FLT3 inhibitor gilteritinib plus azacitidine (GIL + AZA) versus AZA in patients with newly diagnosed FLT3mut+ acute myeloid leukemia (AML) ineligible for intensive induction chemotherapy. Communicated results of an interim analysis of this trial are summarized here.
Eligible patients were initially randomized 1:1:1 to receive either GIL (120 mg/day orally, days 1-28) plus AZA (75 mg/m2/day subcutaneously or intravenously, days 1-7) combination, or AZA alone, or GIL alone during 28-day cycles. Subsequently, the GIL-alone arm was removed due to preferred therapy changes; patients were then randomized 2:1 to receive GIL + AZA or AZA alone. The primary end point was overall survival (OS); key secondary end points were event-free survival (EFS), response rates, safety/tolerability, and pharmacokinetics. The data cutoff date was August 26, 2020.
A total of 123 patients were enrolled in this study; of these, 74 patients received GIL + AZA therapy and 49 received AZA. Baseline characteristics were generally similar between the 2 treatment cohorts. Median follow-up was 9.76 months for GIL + AZA and 17.97 months for AZA. Compared with GIL + AZA, a higher proportion of patients in the AZA arm (20.3% vs 44.9%) received subsequent AML therapy sooner (8.2 months vs 4.5 months); of these, 10 patients received GIL.
There was no difference in OS between the GIL + AZA and AZA arms (9.82 months vs 8.87 months; hazard ratio [HR], 0.916; P = .753); these results may have been confounded by several factors, including subsequent antileukemic therapy, more patients with baseline Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 in the GIL + AZA arm, and study design change. In subgroup analyses, GIL + AZA therapy was associated with improved OS in ECOG PS 0-1 (HR, 0.811) and high FLT3-ITD allelic ratio ≥0.5 (HR, 0.580). Both treatment arms were associated with similar EFS (median EFS, 4.73 vs 2.07 months; HR, 1.175; P = .459). Complete remission (CR) rates were similar for both treatment arms (16.2% vs 14.3%); however, composite CR rates were significantly higher for the GIL + AZA arm (58.1 vs 26.5%; P <.001) versus the AZA arm.
The 2 treatment arms showed comparable overall adverse event (AEs; GIL + AZA, 100%; AZA, 95.7%) and grade ≥3 AE rates (GIL + AZA, 95.9%; AZA, 89.4%). Four deaths due to treatment-related AEs were reported in each arm. The most common treatment-related AEs with GIL + AZA therapy were pyrexia (47.9%) and diarrhea (38.4%).
These results indicate that addition of gilteritinib to AZA led to significantly higher composite CR rates but did not provide an OS advantage compared with AZA alone in patients with newly diagnosed FLT3mut+ AML ineligible for intensive induction chemotherapy, with emergence of no new safety signals.
Source: Wang ES, et al. ASH 2021; abstr 700.