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Potential Off‐Target Effect of Gilteritinib With Venetoclax Decreases Tumor Burden for Patients With Relapsed/Refractory Wild‐Type FLT3 Acute Myeloid Leukemia/Myelodysplastic Neoplasms

Year: 2025

Type: article

Abstract: Many tyrosine kinase inhibitors show nonspecific activity against multiple kinases, causing off‐target effects when used in a broad patient population. This study evaluated the effectiveness of gilteritinib combined with venetoclax in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) or myelodysplastic neoplasms (MDS) with wild‐type FLT3 , who currently lack targeted therapy. After a 28‐day cycle of venetoclax–gilteritinib therapy, one patient with R/R AML and other genetic alterations achieved minimal residual disease (MRD)–positive complete remission (CR) with incomplete hematologic recovery (CRi). Another patient with R/R ASXL1 ‐mutated MDS/AML achieved morphologic leukemia‐free state (MLFS) after one cycle, but cytopenias persisted across two cycles. A patient with R/R TP53 ‐mutated AML related to myelodysplasia did not respond (NR) after two cycles, although the blast percentage in bone marrow (BM) and peripheral blood (PB) decreased by 50%. In a patient with R/R AML carrying an in‐frame bZIP‐mutated CEBPA , NR and disease progression occurred after one cycle, but elevated white blood cell (WBC) counts declined after treatment initiation and lasted for 2 weeks. These findings suggest that combining gilteritinib with venetoclax may reduce tumor burden in R/R AML/MDS patients with wild‐type FLT3 .

Source: Case Reports in Hematology

DOI: 10.1155/crh/4335095