TOPLINE

In patients with FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) acute myeloid leukemia (AML), high-sensitivity sequencing detected measurable residual disease (MRD) around allogeneic transplant, identified those at higher relapse risk, and showed that peritransplant MRD dynamics refined prognosis.

METHODOLOGY

• Researchers conducted a retrospective cohort study to evaluate whether monitoring of FLT3-ITD MRD around allogeneic hematopoietic cell transplantation predicted relapse risk and survival in patients with AML, and whether it could guide conditioning and post-transplant FLT3 inhibitor use.
• The final analysis included 219 adults with FLT3-ITD-mutated AML in morphologic complete remission (median age, 44 years; 50.5% women) who underwent first allogeneic transplant at three Chinese centers between November 2016 and June 2024.
• FLT3-ITD MRD was assessed using polymerase chain reaction-next-generation sequencing (PCR-NGS) in bone marrow collected within 28 days before transplant and/or 28 to 84 days after transplant. Results were compared with multiparameter flow cytometry and capillary electrophoresis.
• Researchers assessed measures including relapse, relapse-free survival, overall survival, and cumulative incidence of relapse. They also recorded conditioning intensity and receipt of post-transplant FLT3 inhibitors.
• Patients were followed for a median duration of 33 months. A 12-week post-transplant landmark analysis assessed how FLT3 inhibitor maintenance affected outcomes, stratified by peritransplant MRD status.

TAKEAWAY

• PCR-NGS detected pretransplant MRD in 32% of patients, whereas capillary electrophoresis detected it in 7.8%, and many capillary electrophoresis-negative cases were PCR-NGS-positive.
• Patients positive for pretransplant molecular MRD had worse outcomes than those negative for MRD for 2-year relapse-free survival (56.8% vs 86.5%), cumulative incidence of relapse (30.0% vs 6.9%), and overall survival (65.9% vs 88.4%; P < .001 for all).
• Patients who stayed MRD-negative throughout had the best 2-year relapse-free survival (92.9%), while those who converted to MRD-positive or remained persistently positive fared worst (44.0% and 34.3%, respectively; P < .001).
• Post-transplant FLT3 inhibitor maintenance was linked to improved relapse-free survival (P = .003), and this benefit was concentrated in patients with detectable MRD, while MRD-negative patients showed no added benefit from maintenance therapy.

IN PRACTICE

"[The] findings underscore the limitations of single-marker MRD monitoring, as residual disease may persist in non-FLT3-ITD compartments. In this context, integration of multitarget genomic approaches or complementary modalities such as flow cytometric MRD is likely to remain important," the authors of the study wrote.

SOURCE

The study was led by Xiaoxia Hu, Shanghai Jiao Tong University School of Medicine, Shanghai, China. It was published online on August 14 in Blood Advances.

LIMITATIONS

The study was retrospective with protocol differences across centers, which may have introduced residual confounding. Most patients had not received frontline FLT3 inhibitors. Most patients received sorafenib and few received gilteritinib, limiting direct comparison.

DISCLOSURES

The study received support from the National Natural Science Foundation of China. The authors declared having no competing financial interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.