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Ref Type Journal Article
PMID (41487332)
Authors Pospiech M, Ngo MP, Alrawashdeh M, Qamar U, Ali A, Tam E, Yaghmour G, Alachkar H, Ladha A
Title Acute Myeloid Leukemia With a Non-Canonical FLT3 V491L Mutation: A Case Report With Ex Vivo FLT3 Inhibitors Sensitivity Testing.
Journal Vol Issue Date Pages Journal Short Title
Journal of medical cases 17 1 2026 Jan 14-20 J Med Cases
URL
Abstract Text Approximately 30% of patients with acute myeloid leukemia (AML) harbor FMS-like tyrosine kinase 3 (FLT3) mutations, which are associated with poor overall survival. Although United States Food and Drug Administration (FDA)-approved FLT3 inhibitors are available, their efficacy against non-canonical FLT3 mutations remains elusive. Here we present a case of a 72-year-old female Jehovah's Witness with newly diagnosed AML carrying a rare pathogenic FLT3 V491L mutation identified by next-generation sequencing. Given the patient's religious beliefs, blood transfusion was not an option, making the patient ineligible for high-intensity chemotherapy and leading to alternative treatment approaches. To our knowledge, this is the first case report of the effectiveness of gilteritinib in an older patient with AML with a non-canonical FLT3 mutation and limitation on blood products usage. Initial treatment with hydroxyurea and leukapheresis followed by azacitidine and venetoclax resulted in an inadequate treatment response. Given the lack of research on the FLT3 V491L mutation, we conducted an ex vivo sensitivity study using the patient's diagnostic bone marrow blasts to assess and compare the anti-leukemic efficacy of midostaurin, quizartinib, and gilteritinib. The ex vivo study revealed the lowest half-maximal inhibitory concentration (IC50) value and the highest number of apoptotic cells in gilteritinib treated patient's blasts under Flt3 ligand-supplemented conditions. An initial clinical improvement with gilteritinib was observed. However, after the third cycle, gilteritinib was substituted with midostaurin because of high copay costs with gilteritinib. Subsequently, an increase in leukemic blasts was observed, and soon after, the patient expired. Treatment of relapsed AML with a non-canonical mutation is challenging due to the lack of data regarding FLT3 inhibitors. This case highlights the potential role of gilteritinib in targeting the rare FLT3 V491L mutation, underscoring the need for further research and improved accessibility to effective therapies.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
FLT3 V491L missense unknown FLT3 V491L lies within the extracellular domain of the Flt3 protein (UniProt.org). V491L has been identified in the scientific literature (PMID: 41487332, PMID: 37680325, PMID: 38502195), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2026).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FLT3 V491L acute myeloid leukemia sensitive Gilteritinib Case Reports/Case Series Actionable In a clinical case study, Xospata (gilteritinib) treatment resulted in disappearance of peripheral blasts in a patient with acute myeloid leukemia harboring FLT3 V491L, and in a preclinical study, inhibited viability of patient-derived acute myeloid leukemia cells in culture (PMID: 41487332). 41487332