Therapeutic Management of Patients with FLT3 + Acute Myeloid Leukemia: Case Reports and Focus on Gilteritinib Monotherapy

Abstract

Acute myeloid leukemia is a malignant disorder of the bone marrow, characterized by differentiation, clonal expansion, and uncontrolled proliferation of malignant myeloid progenitor cells and by several molecular and genetic abnormalities. A mutation of FMS-like tyrosine kinase 3 gene can be observed in about one-third of cases of acute myeloid leukemia. Two FLT3 inhibitors are actually approved for FLT3 mutated acute myeloid leukemia: midostaurin, a multikinase first generation inhibitor with lower affinity for FLT3 binding, and gilteritinib fumarate, a potent second-generation inhibitor of both FLT3-ITD and TKD. Gilteritinib is a new effective and well-tolerated drug for patients with relapsing or refractory FLT3-positive acute myeloid leukemia. Thanks to its efficacy, low toxicity, its good manageability (oral formulation), this drug is suitable for all the patients, including elderly frail patient with concomitant therapies or pre-existing or underlying diseases, and can be used also in the outpatient setting, reducing risks and costs related to the hospitalization. We report and discuss seven cases of different patients with FLT3 positive acute myeloid leukemia successfully managed with gilteritinib in the real clinical practice.

Гилтеритиниб — Новая Возможность В Лечении Рецидивов И Рефрактерных Острых Миелоидных Лейкозов С Мутацией В Гене FLT3: Обзор Литературы И Описание Трех Собственных Клинических Наблюдений

“…У пациента достигнута полная регрессия экстрамедуллярных опухолевых поражений через 4 мес. после начала терапии гилтеритинибом [25].…”

Latest Insights and Progress in the Clinical Management of Elderly Patients with Acute Myeloid Leukemia: From Genetic Advancements to Targeted Treatments

“…Therefore, it is of utmost importance to test for the presence of the FLT3 mutation in relapsed older AML patients, including those who no longer respond to venetoclax/azacytidine combination therapy. Indeed, acquiring the FLT3 mutation during the clonal evolution that characterizes leukemic relapse would make these patients suitable candidates for treatment with the FLT3 inhibitor gilteritib [110][111][112][113], an oral, selectively effective FLT3 inhibitor with single-agent activity in R/R FLT3-mutated AML [111]. In such a setting, gilteritib showed a good safety and tolerability profile [112,113], allowing its use even in fragile or otherwise compromised patients.…”

“…Indeed, acquiring the FLT3 mutation during the clonal evolution that characterizes leukemic relapse would make these patients suitable candidates for treatment with the FLT3 inhibitor gilteritib [110][111][112][113], an oral, selectively effective FLT3 inhibitor with single-agent activity in R/R FLT3-mutated AML [111]. In such a setting, gilteritib showed a good safety and tolerability profile [112,113], allowing its use even in fragile or otherwise compromised patients. Therefore, for eligible older patients with R/R AML, harboring FLT3 mutations, gilteritinib represents the most critical current salvage option.…”

Advancements in Myeloid Leukemia Treatment: A Comprehensive Update

“…Genetics and molecular insight Genetics and molecular insights play a crucial role in understanding and advancing research on myeloid leukemia. Myeloid leukemia is a malignant disorder characterized by the uncontrolled proliferation of malignant myeloid progenitor cells and various genetic and molecular abnormalities [81]. The molecular diversity and evolution of acute myeloid leukemia (AML) have been extensively studied, providing valuable insights into the disease.…”