In the phase III MORPHO trial reported in the Journal of Clinical Oncology, Mark J. Levis, MD, PhD, and colleagues found that the FLT3 inhibitor gilteritinib showed activity as post–allogeneic hematopoietic cell transplantation (HCT) maintenance among patients with FLT3-ITD–mutated acute myeloid leukemia with measurable residual disease (MRD) before or after HCT.
Mark J. Levis, MD, PhD
Study Details
In the double-blind trial, 356 adults from sites in 16 countries in first remission underwent HCT and were randomly assigned between August 2017 and July 2020 to receive gilteritinib maintenance at 120 mg (n = 178) or placebo (n = 178) once daily for 24 months after HCT. The primary endpoint was relapse-free survival.
Key Findings
At 2 years, gilteritinib was associated with a numeric advantage in recurrence-free survival vs placebo: 77.2% (95% confidence interval [CI] = 70.1%–82.8%) vs 69.9% (95% CI = 62.4%–76.2%; hazard ratio [HR] = 0.679, 95% CI = 0.459–1.005, P = .0518).
A total of 50.5% of patients had MRD before or after HCT. Prespecified analysis among these patients showed superior 2-year recurrence-free survival with gilteritinib vs placebo (HR = 0.515, 95% CI = 0.316–0.838, P = .0065). No benefit of gilteritinib was observed among patients without detectable MRD (HR = 1.213, 95% CI = 0.616–2.387, P = .575).
Grade 2 to 4 acute graft-vs-host disease (GVHD) occurred in 18.5% vs 20.3% of patients (P = .6157); grade 2 to 4 chronic GVHD occurred in 52.2% vs 42.4% (P = .181). Grade ≥ 3 adverse events occurred in 82% vs 53% of patients, with the most common in the gilteritinib group being decreased neutrophils (36% vs 13% in the placebo group), decreased platelets (21% vs 11%), and decreased white blood cells (10% vs 2%).
The investigators concluded: “Although the overall improvement in relapse-free survival was not statistically significant, relapse-free survival was higher for participants with detectable FLT3-ITD MRD pre- or post-HCT who received gilteritinib treatment. To our knowledge, these data are among the first to support the effectiveness of MRD-based post-HCT therapy.”
Dr. Levis, of Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by the U.S. National Cancer Institute and Astellas Pharma Global Development Inc. For full disclosures of the study authors, visit ascopubs.org.
