Is Gilteritinib Effective as Post-Transplant Maintenance in Patients With FLT3-ITD-Mutated AML?

Treatment with the FLT3 inhibitor gilteritinib improved relapse-free survival (RFS) after allogeneic hematopoietic stem cell transplantation (AHSCT) in a subset of patients with FLT3-ITD-mutated AML, according to data published in the Journal of Clinical Oncology.

Additionally, the authors, led by Mark Levis, MD, PhD, of Johns Hopkins University, noted that the results demonstrated that molecular measurable residual disease (MRD) might be used to guide treatment in patients with AML undergoing AHSCT.

Trial Design, Results

In a randomized trial of post-AHSCT maintenance with gilteritinib, 356 adults with FLT3-ITD-mutated AML in first remission underwent AHSCT and were randomly assigned to placebo or 120 mg once daily gilteritinib for 24 months after transplant. The primary endpoint was RFS, with secondary endpoints including overall survival (OS) and the effect of detection of MRD pre- and post-AHSCT on RFS and OS.

Although RFS was higher in the gilteritinib arm, the difference was not statistically significant (hazard ratio [HR], 0.679; 95% CI, 0.459-1.005; two-sided P=.0518). However, 50.5% of participants had MRD detectable pre- or post-HSCT, and, in a prespecified subgroup analysis, gilteritinib was beneficial in this population (HR, 0.515; 95% CI, 0.316-0.838; P=.0065). Those without detectable MRD showed no benefit (HR, 1.213; 95% CI, 0.616-2.387; P=.575).

“Although the overall improvement in RFS was not statistically significant, RFS was higher for participants with detectable FLT3-ITD MRD pre- or post-[AHSCT] who received gilteritinib treatment,” the authors wrote. “These prospective results establish FLT3-ITD mutations as essential markers of MRD and illustrate how molecular MRD can be used to guide the therapy of patients with AML undergoing [AHSCT].”

Reference

Levis MJ, Hamadani M, Logan B, et al. Gilteritinib as post-transplant maintenance for acute myeloid leukemia with internal tandem duplication mutation of FLT3. J Clin Oncol. 2024. doi:10.1200/JCO.23.02474