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Gilteritinib Effective for Post-Transplant Maintenance for Acute Myeloid Leukemia

May 24, 2024

June 2024

Lara C. Pullen, PhD

Lara C. Pullen, PhD, is a freelance medical writer in Chicago, Illinois.

While standard polymerase chain reaction (PCR) can detect the internal tandem duplication mutation of FLT3 (FLT3-ITD) that is common in patients with acute myeloid leukemia (AML), the mutations detected this way are generally considered unreliable markers of measurable residual disease (MRD). In contrast, recent studies have indicated that PCR and next-generation sequencing (NGS) can together detect low levels of FLT3-ITD mutations in AML that is in remission, and the presence of these mutations correlates with relapse.

Now, a new study led by the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) has found that while the FLT3 inhibitor gilteritinib did not improve the relapse-free survival (RFS) when used as a post-transplant maintenance for AML in the overall study population, RFS was higher for participants with PCR-NGS detectable FLT3-ITD MRD pre- or post-hematopoietic cell transplantation (HCT) who received gilteritinib treatment. Mark J. Levis, MD, PhD, professor of oncology at Johns Hopkins University in Baltimore, and colleagues have thus provided some of the first data to support the effectiveness of MRD-based post-HCT therapy. They published their findings in the Journal of Clinical Oncology.

The investigators conducted the study to investigate the assumption that all patients with FLT3-ITD AML should receive an FLT3 inhibitor post-HCT. They randomly assigned 356 adults with FLT3-ITD AML in first remission who had undergone allogeneic HCT (alloHCT) to receive gilteritinib or placebo. In their primary analysis, they found no statistically significant RFS benefit from post-transplant treatment with gilteritinib (hazard ratio [HR] = 0.679; 95% CI 0.459-1.005; two-sided p=0.0518).

Half of the patients (50.5%) in the study had detectable MRD pre- and post-HCT, and when the researchers performed a prespecified subgroup analysis, they found that gilteritinib was beneficial in this population (HR=0.515; 95% CI 0.316-0.838; p=0.0065). Thus, participants with FLT3-ITD AML who underwent HCT in first remission with peri-HCT detectable FLT3-ITD MRD benefitted from post-HCT gilteritinib. In contrast, patients who were in deep remission experienced no benefit from post-transplant giltieritinib therapy. For the 60% of participants who received an FLT3 inhibitor pre-HCT, gilteritinib conferred an RFS benefit compared with placebo (HR=0.598; p=0.0436), but there was no difference in the rate of detectable pre-HCT MRD between those who did and did not receive pre-HCT FLT3 inhibition (48.3% vs. 52.1%, respectively). The authors did not describe any limitations to their study.

Mehdi Hamadani, MD, professor of medicine at the Medical College of Wisconsin in Milwaukee and coauthor of the study, said that although European and Chinese studies have addressed the benefit of post-transplant treatment with gilteritinib, the findings from these previous studies are not necessarily relevant to current treatment regimens because they were performed at a time when FLT3 inhibitors were not consistently part of the pretransplant induction regimens. Moreover, the previous studies were not designed to answer the question of which, if any, patients benefit from post-transplant treatment. In contrast, Dr. Hamadani said that his study enrolled patients who frequently received FLT3 inhibitors as part of their pretransplant regimen. The current study also had the advantage of being designed for the secondary endpoint of the effect of MRD pre- and post-HCT on RFS and overall survival.

This secondary analysis found that post- transplant treatment with gilteritinib only benefited patients with detectable MRD. “That’s what we were anticipating,” Dr. Hamadani said. “We believed that maintenance therapies may not benefit everybody, and that’s what the study showed.” He pointed out that the new findings will allow clinicians to spare some patients both the toxicity (especially myelosuppression) and the cost of treatment with gilteritinib. In their discussion, the authors proposed that FLT3 inhibition during induction and/or consolidation might select for participants who are more likely to benefit from post-HCT FLT3 inhibition.

The study also identified distinct regional differences in outcomes. Gilteritinib was beneficial in North America, was of minimal benefit in Asia and the rest of the world, and had a mildly negative effect in Europe. “There were definite regional differences, but we still don’t have a strong biological reason for them.” One possibility, Dr. Hamadani  said, is that differences in the way HCTs are performed around the world may affect the benefits patients experience from post-transplant treatment with gilteritinib.

Any conflicts of interest declared by the authors can be found in the original article.


Levis MJ, Hamadani M, Logan B, et al. Gilteritinib as post-transplant maintenance for acute myeloid leukemia with internal tandem duplication mutation of FLT3 [published online ahead of print, 2024 March 12]. J Clin Oncol.  doi: 10.1200/JCO.23.02474.


A key advancement in the treatment of AML has been the development of targeted approaches to the disease. FLT3-ITD mutations are associated with a high risk for relapse, and the development of FLT3 inhibitors has improved remission rates and alloHCT outcomes for this high-risk subset of disease. A key question with alloHCT was whether the addition of FLT3 inhibitors in the post-transplant setting could further enhance the curative effect of transplant by reducing relapse.

In this phase III double-blind placebo-controlled trial, participants with FLT3-ITD AML in first remission receiving HCT were randomized to receive gilteritinib or placebo as maintenance therapy after HCT. Maintenance therapy was continued for 24 months, the timeframe during which most relapse events typically occur. Although RFS, the primary endpoint, was higher in the gilteritinib arm, the difference was not statistically significant (p=0.0518). However, the presence of MRD at HCT or early post-HCT (prior to maintenance) proved to be an important clinical factor to differentiate the use of FLT3 inhibition. Gilteritinib significantly improved RFS for participants with detectable MRD, while no benefit was observed in participants without MRD.

The investigators should be congratulated on designing and completing this large study, which was of high priority to the global HCT community. A strength of the trial was its large size (356 participants) and wide participation (122 centers in 16 countries). Interestingly, rather than having a unified approach to FLT3 inhibition that can be broadly applied to all centers, subanalyses identified significant differences in RFS when comparing outcomes in North America, Europe, Asia, and other countries, which reflects how patient selection and treatment approaches are not uniform globally.

The addition of FLT3 inhibition as maintenance therapy ultimately is a nuanced decision, which needs to be made in an individualized manner. Our ability to have in-depth PCR-NGS MRD testing and targeted agents, such as gilteritinib, and the results of a randomized trials, like BMT CTN 1506 MORPHO trial, provides clinicians the tools and information needed to give the highest level of care to our patients. For patients with detectable MRD, gilteritinib should be considered standard of care for transplant centers in North America.

Zachariah M. DeFilipp, MD
Director, BMT Clinical Research
Massachusetts General Hospital

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