Post-HSCT gilteritinib resumption improves OS in R/R FLT3mut+ AML: Pooled analysis of the phase 3 ADMIRAL and COMMODORE trials

29 Jan 2026

STUDY DESIGN

Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment for patients with relapsed/refractory FMS-like tyrosine kinase 3-mutated acute myeloid leukemia (R/R FLT3^mut+ AML).¹ Patients with R/R FLT3^mut+AML have an increased risk of post-HSCT relapse compared with those in first complete remission (CR1).¹ Evidence indicates that patients with FLT3^mut+AML in CR1 benefit from FLT3 inhibitor therapy resumption following HSCT, including gilteritinib, particularly in the presence of measurable residual disease (MRD) during the peri-transplant period.¹ However, these findings cannot be extrapolated to patients with R/R FLT3^mut+AML undergoing HSCT, where data on the efficacy of post-HSCT FLT3 inhibitor resumption remain limited.¹

In view of these findings, a post-hoc pooled analysis of the phase 3 ADMIRAL and COMMODORE studies was conducted to assess the overall survival (OS) in patients with R/R FLT3^mut+AML who underwent HSCT, including those who resumed gilteritinib treatment following transplantation.¹ All randomized patients who received gilteritinib or salvage chemotherapy from both studies were pooled for analysis.¹ Patients were stratified according to HSCT status, pre-HSCT disease response, and post-HSCT gilteritinib resumption, independent of initial treatment assignment.¹

Of the total 647 patients included, 125 underwent HSCT, and 95 of these were randomized to the gilteritinib arm.¹ Among the gilteritinib-treated HSCT recipients, 58 resumed gilteritinib post-transplantation.¹ Only patients previously treated with gilteritinib were eligible to resume post-HSCT therapy if they survived 30-90 days following HSCT, achieved successful engraftment without transfusion support (absolute neutrophil count ≥500/mm³ and platelet count ≥20,000/mm³), had no grade ≥2 acute graft-versus-host disease, and attained a composite complete remission (CRc).¹

A landmark analysis was subsequently conducted within the gilteritinib arm, including only patients who remained relapse-free for at least 60 days after HSCT.¹ The key outcomes assessed were OS evaluated by HSCT status, pre-HSCT response irrespective of treatment, and relapse-free survival (RFS) and OS by gilteritinib resumption post-HSCT among gilteritinib-treated patients¹

FINDINGS

Efficacy:

The key outcomes assessed were OS evaluated by HSCT status, pre-HSCT response irrespective of treatment, and relapse-free survival (RFS) and OS by gilteritinib resumption post-HSCT among gilteritinib-treated patients¹

- OS by HSCT status¹

- - Median OS was significantly longer with 24.1 months (95% CI: 18.8-not estimable [NE]) in patients who underwent HSCT vs. 7.4 months (95% CI: 6.6-8.3) in those who did not (p<0.0001)
  - The 36-month OS rate was 44.9% (95% CI: 36.6-55.1) in HSCT recipients vs. 8.1% (95% CI: 5.7-11.4) in the non-HSCT group

OS by pre-HSCT response¹

- Among HSCT recipients, patients who achieved CRc prior to HSCT had a numerically longer median OS (NE; 95% CI: 19.3-NE) vs. those who did not achieve CRc (21.1 months; 95% CI: 18.1-NE), although the difference was not statistically significant (p=0.3327)
- The OS rate at 36 months was 52.7% (95% CI: 42.4-65.5) in patients who achieved CRc vs. 38.4% (95% CI: 26.2-56.3) in those who did not

RFS and OS by gilteritinib resumption status post-HSCT¹

- Among patients who remained relapse-free at day 60 post-HSCT, 72.0% of those who resumed gilteritinib achieved CRc pre-HSCT vs. 40.7% of those who did not resume
- Gilteritinib resumption was associated with a lower risk of relapse or death; median RFS was NE vs. 8.4 months in patients without resumption (HR=0.4; 95% CI: 0.2-0.7)
- Results stratified by post-HSCT CRc and gilteritinib resumption status showed a numerical RFS benefit in patients with gilteritinib resumption post-transplant (HR=0.5; 95% CI: 0.1-2.0)
- Gilteritinib resumption was associated with a lower risk of death, with a median OS of NE vs. 10.1 months in patients without resumption (HR=0.4; 95% CI: 0.2-0.8)
- Results stratified by post-HSCT CRc and gilteritinib resumption status showed a numerical OS benefit in patients who resumed gilteritinib post-transplant (HR=0.9; 95% CI: 0.1-6.3)

Safety:

The adverse event (AE) profile was consistent with the established safety profile of gilteritinib¹
The most frequently reported AEs were increased alanine aminotransferase and aspartate aminotransferase levels, pyrexia, diarrhea, pneumonia, and anemia¹

“Long-term survival was associated with HSCT reception in R/R FLT3^mut+AML, particularly in patients achieving CRc pre-transplant, with a reduced risk of relapse or death among those who resumed gilteritinib post-HSCT.”

Professor Wang Jianxiang
Chinese Academy of Medical Sciences and Peking Union Medical College,
Tianjin, China

References

Wang J, et al. Outcomes of patients with relapsed/refractory FLT3^mut+ acute myeloid leukemia who resumed gilteritinib therapy after HSCT: Post hoc analysis of the ADMIRAL and COMMODORE trials. Presented at the American Society of Hematology (ASH) Annual Meeting 2025; December 6-9, 2025.