Post-HSCT Gilteritinib May Improve Outcomes in R/R FLT3-Mutated AML

Targeted maintenance therapy with gilteritinib (Xospata) following allogeneic hematopoietic stem cell transplantation (HSCT) may significantly improve survival outcomes for patients with relapsed or refractory (R/R) FLT3-mutated acute myeloid leukemia (AML), according to findings from a new systematic review in Leukemia Research.¹

Drawing on evidence from 8 studies, including 2 randomized controlled trials and 6 observational cohorts, the review encompassed 134 adult patients with R/R FLT3-mutated AML. The findings suggest that gilteritinib maintenance after HSCT is associated with 1-year overall survival (OS) rates ranging from 72.3% to 100% and 2-year OS rates between 55.8% and 60.0%.

Additionally, 1- and 2-year relapse-free survival rates following HSCT ranged from 46.7% to 100% and 55.8% to 60.0%, respectively. These results indicate a potential survival advantage with gilteritinib compared with historical cohorts not receiving maintenance therapy, although researchers cautioned that the limited sample size precludes definitive conclusions.

“Overall, the [review] findings suggest that using gilteritinib posttransplantation may provide desirable improvements in important clinical outcomes for patients with FLT3-mutated R/R AML, who are known to have a poor prognosis,” wrote authors Hou et al in the publication.¹

The authors put forth a possible biological rationale for the observed survival advantage. They explain that by continuously inhibiting the FLT3 tyrosine kinase with a highly selective second-generation inhibitor like gilteritinib, normal blood cell production can be restored in patients who may still carry residual FLT3-driven leukemia cells, thereby reducing relapse risk and consequently clinical outcomes.

Safety Profile: GVHD

A critical component of posttransplant care is the management of adverse events, particularly as patients are already recovering from the toxicities of conditioning regimens and the risks of graft-vs-host disease (GVHD).

Of the included studies, 4 reported GVHD events. In 2 studies, acute GVHD was reported at rates ranging from approximately 8% to 14%, while chronic GVHD occurred in about 17% to 29% of patients in studies that specified subtype. Other reports described unspecified GVHD in roughly 20% to 38% of patients. In the controlled setting, severity grading showed that about one-third of patients experienced grade 2 or higher GVHD, with around 10% developing grade 3 or higher events.

Across studies, the authors noted a lack of information about relevant safety end points beyond GVHD, highlighting the need for more comprehensive reporting of long-term toxicities, drug interactions, and quality-of-life outcomes.

Bridging the Evidence Gap in R/R AML

Patients with AML harboring FLT3 mutations face a notoriously poor prognosis characterized by high relapse rates even after achieving remission and undergoing HSCT. While data from the phase 3 MORPHO trial (NCT02997202) recently suggested the potential benefit of gilteritinib maintenance for newly diagnosed patients with FLT3-mutated AML in first complete remission posttransplant,² its role in the R/R setting has remained less defined.

The present review sought to address this evidence gap by collating outcomes specifically for those who had already experienced treatment failure or relapse prior to transplant. As a biologically high-risk population that is often underrepresented in prospective clinical trials, the review provides preliminary but clinically meaningful insights into a setting where therapeutic guidance is currently limited and largely extrapolated from frontline disease.

Collectively, the results suggest that gilteritinib maintenance may represent a viable strategy to improve survival outcomes in this population, potentially shifting posttransplant management toward a more proactive, targeted maintenance approach. The authors emphasize, however, the need for large, prospective randomized trials focused specifically on the R/R population to validate these findings and to better define the optimal dosing, timing, and duration of maintenance therapy.

Nevertheless, the emerging evidence signals a promising step toward improving outcomes in a historically difficult-to-treat population.

REFERENCES

1. Hou HA, Getta B, Ahn JS, et al. Outcomes of patients with R/R FLT3mut+ AML treated with maintenance gilteritinib therapy after hematopoietic stem cell transplantation. Leukemia Res. 2026;162:108186. doi: 10.1016/j.leukres.2026.108186

2. Levis MJ, Hamadani M, Logan B, et al. Gilteritinib as post-transplant maintenance for AML with internal tandem duplication mutation of FLT3. J Clin Oncol. 2024;42(15):1766-1775. doi:10.1200/jco.23.02474