A Review of FLT3 Kinase Inhibitors in AML.

Acute myeloid leukemia (AML) is a highly aggressive illness distinguished by the accumulation of abnormal hematopoietic precursors in both the bone marrow and peripheral blood. The prevalence of FLT3 gene mutations is high and escalates the probability of relapse and mortality. The survival rates for AML patients, particularly those over 65, are low. FLT3 mutation screening at diagnosis is mandatory, and FLT3 inhibitors are crucial in treating AML patients with mutations. There are two categories of FLT3 mutations: FLT3-ITD located in the juxtamembrane domain and FLT3-TKD in the tyrosine kinase domain. FLT3-ITD is the most common type, affecting nearly a quarter of patients, whereas FLT3-TKD only affects 6-8% of patients. FLT3 inhibitors are now crucial in treating AML patients with FLT3 mutations. When dealing with FLT3-mutated AML, the recommended course of treatment typically involves chemotherapy and midostaurin, followed by allogeneic hematopoietic cell transplantation (HCT) to maximize the likelihood of success. Maintenance therapy can lower the risk of relapse, and gilteritinib is a better option than salvage chemotherapy for relapsed or refractory cases. Clinical trials for new or combined therapies are the most effective approach. This review discusses treatment options for patients with FLT3-mutated AML, including induction chemotherapy and options for relapsed or refractory disease. Additional treatment options may become available as more studies are conducted based on the patient's condition and susceptibility.

APPLY: A prospective observational study of clinical practice patterns of darbepoetin alfa use in patients with chemotherapy-induced anemia in Romania.

PURPOSE: The primary objective of this study was to evaluate the compliance of Romanian physicians with the national therapeutic protocol and international guidelines on treatment with erythropoiesis-stimulating agents in anemic cancer patients receiving chemotherapy. The secondary objective was to assess the hemoglobin (Hb) level change due to anemia treatment and safety of darbepoetin alfa. METHODS: This was a single-arm, prospective, longitudinal, multicenter, observational study in patients with nonmyeloid malignancies and symptomatic chemotherapy-induced anemia treated concomitantly with darbepoetin alfa. Patients were followed for the duration of chemotherapy, but no shorter than three and no longer than eight cycles, irrespective of their exposure to darbepoetin alfa. RESULTS: In this study, 497 patients with a mean age of 60.6 years were analyzed. Most patients (80.7%) were initiated on darbepoetin alfa at a Hb of 9-11 g/dL, congruent with recommendations. The median Hb increased by 0.9 g/dL between baseline and week 12. Hb target achievement was higher among patients treated according to guidelines than those initiated at Hb < 9 g/dL. A similar trend was observed for red blood cell transfusion requirements. No new safety signals were reported for darbepoetin alfa. CONCLUSIONS: The majority of patients were treated according to national and international recommendations. Guideline adherence was associated with more frequent achievement of Hb targets and lower red blood cell transfusion requirements compared with patients starting anemia treatment with darbepoetin alfa at lower-than-recommended Hb levels.