Gilteritinib-Associated Hypertriglyceridemia During Acute Myeloid Leukemia Triplet Therapy in a 52-Year-Old Man: A...

Acute myeloid leukemia (AML) harboring a FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutation is characterized by a more aggressive clinical course, a higher likelihood of disease recurrence, and inferior survival outcomes. The introduction of targeted agents such as gilteritinib has expanded therapeutic options for patients with FLT3-mutated AML; however, the spectrum of rare treatment-related toxicities remains incompletely defined. We describe a case of profound hypertriglyceridemia that developed during treatment with a combination of azacitidine, venetoclax, and gilteritinib. A 52-year-old man presented with constitutional symptoms, marked leukocytosis, splenomegaly, and bone marrow findings consistent with AML exhibiting monocytic differentiation. Molecular analysis identified coexisting FLT3-ITD, nucleophosmin 1 (NPM1), and DNA methyltransferase 3A (DNMT3A) mutations. Owing to concomitant fungal pneumonia and unsuitability for intensive induction chemotherapy, he was treated with a modified regimen comprising azacitidine, venetoclax, and gilteritinib. The patient's baseline lipid profile was within normal limits. Following two cycles of induction therapy, a bone marrow aspirate was done. Serum triglyceride levels were found to be severely elevated at 6,964 mg/dL. Given the patient's prior episode of pancreatitis, this abnormality was considered clinically significant. Gilteritinib, venetoclax, and isavuconazole were discontinued, and lipid-lowering therapy with rosuvastatin and fenofibrate was commenced. Triglyceride concentrations progressively declined and returned to near-normal levels within one month. This report draws attention to a potentially serious and insufficiently recognized metabolic complication associated with FLT3 inhibitor-based combination therapy. It also underscores the importance of routine lipid surveillance, particularly in patients receiving concomitant azole antifungal agents.