# Relapse following FLT3 inhibitor cessation in FLT3-ITD-positive AML: lessons from two clinical cases

**Authors:** Julia-Annabell Georgi, Christoph Röllig, Johannes Schetelig, Christian Thiede, Sascha Brückmann, Martin Bornhäuser, Jan Moritz Middeke

PMC · DOI: 10.1007/s00277-026-06776-w · 2026-02-04

## TL;DR

This paper discusses two cases of AML patients who relapsed after stopping FLT3 inhibitors, highlighting the need for better guidelines on how long to continue the treatment.

## Contribution

The paper presents two clinical cases to emphasize the lack of evidence-based strategies for discontinuing FLT3 inhibitors in FLT3-ITD AML.

## Key findings

- Two FLT3-ITD AML patients relapsed after discontinuing prolonged FLT3 inhibitor therapy.
- Current guidelines for FLT3 inhibitor duration are insufficient and based on trial protocols.
- There is a need for systematic evaluation to determine safe discontinuation strategies.

## Abstract

The clinical success of FLT3 inhibitors has led to their steadily increasing use in the treatment of acute myeloid leukemia (AML), both in the relapsed/refractory setting and as post-transplant maintenance. Despite their expanding application, there is currently no guidance on the optimal duration of therapy or the feasibility of discontinuation. In the maintenance context, current practice is largely based on trial protocols with predefined treatment periods, yet relapses after cessation have been documented. Similarly, in the relapsed/refractory setting, the management of long-term responders to FLT3-directed monotherapy lacks evidence-based guidance.

We report two cases of FLT3-ITD AML patients with relapse after discontinuation of prolonged FLT3 inhibitor therapy, despite sustained remission prior to withdrawal. As such scenarios remain insufficiently characterized in the literature, these case vignettes are presented to highlight the unresolved challenge of defining the appropriate duration of FLT3 inhibitor therapy and to underscore the need for systematic evaluation to establish evidence-based strategies for safe discontinuation or extended administration.

## Linked entities

- **Genes:** FLT3 (fms related receptor tyrosine kinase 3) [NCBI Gene 2322]
- **Diseases:** acute myeloid leukemia (MONDO:0015667), AML (MONDO:0018874)

## Full-text entities

- **Genes:** CD19 (CD19 molecule) [NCBI Gene 930] {aka B4, CVID3}, NPM1 (nucleophosmin 1) [NCBI Gene 4869] {aka B23, NPM}, ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase) [NCBI Gene 25] {aka ABL, BCR-ABL, CHDSKM, JTK7, bcr/abl, c-ABL}, PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788] {aka B220, CD45, CD45R, GP180, IMD105, L-CA}, MDM2 (MDM2 proto-oncogene) [NCBI Gene 4193] {aka ACTFS, HDMX, LSKB, hdm2}, FLT3 (fms related receptor tyrosine kinase 3) [NCBI Gene 2322] {aka CD135, FLK-2, FLK2, STK1}, CD33 (CD33 molecule) [NCBI Gene 945] {aka CD33rSiglec, SIGLEC-3, SIGLEC3, p67}, MPO (myeloperoxidase) [NCBI Gene 4353]
- **Diseases:** thrombocytopenia (MESH:D013921), leukemic (MESH:D007938), infections (MESH:D007239), GvHD (MESH:D006086), hematologic (MESH:D006402), anemia (MESH:D000740), back pain (MESH:D001416), gait disturbance (MESH:D020233), undifferentiated hematologic neoplasm (MESH:D019337), atrial fibrillation (MESH:D001281), AML (MESH:D015470)
- **Chemicals:** FLT3i (-), fludarabine (MESH:C024352), daunorubicin (MESH:D003630), Gilteritinib (MESH:C000609080), cyclophosphamide (MESH:D003520), mycophenolate mofetil (MESH:D009173), cytarabine (MESH:D003561), tacrolimus (MESH:D016559), idarubicin (MESH:D015255), methotrexate (MESH:D008727), idasanutlin (MESH:C586849), midostaurin (MESH:C059539), busulfan (MESH:D002066), cyclosporine A (MESH:D016572)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12872662/full.md

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Source: https://tomesphere.com/paper/PMC12872662