Survival improvement of patients with FLT3 mutated acute myeloid leukemia: results from a prospective 9 years cohort

Oñate, Guadalupe; Pratcorona, Marta; Garrido, Ana; Artigas-Baleri, Alícia; Bataller, Àlex; Tormo, Mar; Arnán, Montserrat; Vives, Susana; Coll, Rosa; Salamero, Olga; Vall-Llovera, Ferrán; Sampol, Antònia; Garcia, Antoni; Cervera, Marta; Ávila, Sara García; Bargay, Joan; Ortı́n, Xavier; Nomdedeu, Josep; Esteve, Jordi; Sierra, Jordi

doi:10.1038/s41408-023-00839-1

Cited by 6 publications

(3 citation statements)

References 35 publications

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“…Several factors, including the allelic ratio of the mutation, the presence of co-mutations, and the insertion site, influence the outcome for patients with FLT3-ITD mutation [18]. Isolated FLT3-ITD mutation cannot be responsible for the occurrence of acute myeloblastic leukemia, and it must be associated with other molecular abnormalities: NPM1 mutation, AML1-ETO gene fusion, NUP98 fusion, CBFβ-SMMHC fusion gene, and TET 2 deletion [19].…”

Section: Leukemogenesis In Flt3-positive Amlmentioning

confidence: 99%

A Review of FLT3 Kinase Inhibitors in AML

Negotei,

Colita,

Mitu

et al. 2023

JCM

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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.

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Section: Leukemogenesis In Flt3-positive Amlmentioning

confidence: 99%

A Review of FLT3 Kinase Inhibitors in AML

Negotei,

Colita,

Mitu

et al. 2023

JCM

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“…In this study, only 83/440 patients (19%) received at least one consolidation with HDAC, as allograft was intended in all patients achieving CR after induction [65]. Retrospective studies have shown the real-life benefit of the addition of midostaurin to intensive treatment in patients with FLT3-mutated AML [66,67].…”

Section: Midostaurinmentioning

confidence: 99%

Optimal Post-Remission Consolidation Therapy in Patients with AML

Jimenez-Chillon,

Dillon,

Russell

2023

Acta Haematol

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Background: Despite recent advances, 40–85% of patients with acute myeloid leukaemia (AML) achieve complete remission after intensive chemotherapy. However, without optimal treatment after remission, the risk of relapse remains high. Summary: A variable number of consolidation cycles consisting of intermediate doses of cytarabine are the most commonly used regimens in low-intermediate-risk AML, while patients at higher risk of relapse should consolidate response by proceeding to HSCT. Different post-consolidation (maintenance therapies) have demonstrated their benefit in prolonging relapse-free survival, and others are still under investigation. Careful consideration should be given to which patients benefit most from each of these interventions, considering that the risk of relapse is dynamic. Key Messages: Patients consolidated with chemotherapy should receive either 2 courses of HDAC or no more than 3–4 cycles of IDAC with dose reduction in patients over 60 years. Patients with mutated FLT3 AML benefit from post-consolidation maintenance with FLT3 inhibitors, and selected patients not fit for adequate consolidation may benefit from CC-468 maintenance. Patients at higher risk of relapse should proceed to allogeneic SCT as soon as possible, opting for a more intensive conditioning in patients younger than 55 years. However, autologous HSCT may still have role in favourable-risk MRD-negative AML. Multiple treatment options targeting MRD are emerging, either as definitive treatment or as a bridge to allogeneic transplantation, and are likely to become increasingly relevant.

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“…In particular, TKIs such as midostaurin, gilteritinib, and sorafenib have shown promising results at various stages of AML therapy, including first-line treatment, relapse, and maintenance after allogeneic stem cell transplantation. 5 , 6 , 7 , 8 , 9 These benefits are particularly evident in patients harboring FLT 3 -ITD or TKD mutations. Therefore, the identification of pathogenic FLT3 mutations that can be targeted by TKIs has significant therapeutic implications for the treatment of AML.…”

mentioning

confidence: 99%

Very short insertions in the FLT3 gene are of therapeutic significance in acute myeloid leukemia

Tamburini,

Mouche,

Larrue

et al. 2023

Blood Advances

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Survival improvement of patients with FLT3 mutated acute myeloid leukemia: results from a prospective 9 years cohort

Cited by 6 publications

References 35 publications

A Review of FLT3 Kinase Inhibitors in AML

A Review of FLT3 Kinase Inhibitors in AML

Optimal Post-Remission Consolidation Therapy in Patients with AML

Very short insertions in the FLT3 gene are of therapeutic significance in acute myeloid leukemia

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