News - FLT3-ITD mutation

16h

HOVON 156 AML: A Study of Gilteritinib Versus Midostaurin in Combination With Induction and Consolidation Therapy Followed by One-year Maintenance in Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndromes With Excess Blasts-2 With FLT3 Mutations Eligible for Intensive Chemotherapy (clinicaltrials.gov)

P3, N=777, Active, not recruiting, Stichting Hemato-Oncologie voor Volwassenen Nederland | Trial primary completion date: Dec 2024 --> Oct 2025

16 hours ago

Trial primary completion date • Combination therapy

FLT3 (Fms-related tyrosine kinase 3)

FLT3-ITD mutation • FLT3 mutation • FLT3-TKD mutation

Xospata (gilteritinib) • Rydapt (midostaurin)

Salvage Therapy with Second-Generation Inhibitors for FLT3 Mutated Acute Myeloid Leukemia: A Real-World Study by the CETLAM and PETHEMA Groups. (PubMed, Cancers (Basel))

Gilter/quizar monotherapy are effective and tolerable options for patients with R/R FLT3mut AML in a real-world setting. Response and toxicity rates are similar to those reported in the phase 3 trials, despite the more heterogeneous nature of the study population.

1 day ago

Journal • Real-world evidence • Real-world

FLT3 (Fms-related tyrosine kinase 3)

FLT3-ITD mutation • FLT3 mutation

Xospata (gilteritinib) • Rydapt (midostaurin) • Vanflyta (quizartinib)

Prognostic value of myeloid-derived suppressor-like cells in acute myeloid leukemia: insights from immunophenotyping and clinical correlations. (PubMed, Immunol Res)

Notably, we observed confirmational evidence of CD36 relevance in the AML context, which has emerged recently as a potential marker for PMN-MDSCs. Our study highlights significant findings associating increased MDSC-like subsets and poor prognostic factors in AML.

4 days ago

Retrospective data • Journal

FLT3 (Fms-related tyrosine kinase 3) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • CD36 (thrombospondin receptor) • ITGAM (Integrin, alpha M) • MME (Membrane Metalloendopeptidase) • ANPEP (Alanyl Aminopeptidase, Membrane)

FLT3-ITD mutation

All-trans retinoic acid potentiates cell death induced by quizartinib in acute myeloid leukemia with FLT3-ITD mutations. (PubMed, Ann Hematol)

All-trans retinoic acid (ATRA) is well known for its effectiveness in acute promyelocytic leukemia (APL) treatment and has already been shown to have synergistic effects combined with another TKI, sorafenib. Finally, in a xenotransplantation model ATRA plus AC220 was more efficient to reduce the leukemic burden than monotherapy with ATRA or AC220. Taken together, our results are a proof of the concept that ATRA and AC220 have synergistic anti-leukemic effects.

7 days ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • BECN1 (Beclin 1)

FLT3-ITD mutation

sorafenib • Vanflyta (quizartinib)

Quantification of the FLT3 internal tandem duplication is a reliable marker for monitoring measurable residual disease in acute myeloid leukemia with FLT3-ITD mutations. (PubMed, Bone Marrow Transplant)

No abstract available

8 days ago

Journal

FLT3 (Fms-related tyrosine kinase 3)

FLT3-ITD mutation

The Dual PIM/FLT3 Inhibitor MEN1703 Combines Synergistically With Gilteritinib in FLT3-ITD-Mutant Acute Myeloid Leukaemia. (PubMed, J Cell Mol Med)

We also show that MEN1703 downregulates stromal cytokines that promote cytokine-mediated resistance of AML blast cells to FLT3 inhibition. These results demonstrate the importance of the combination approach to overcome microenvironment-mediated resistance to FLT3 inhibitors.

9 days ago

Journal

FLT3 (Fms-related tyrosine kinase 3)

FLT3-ITD mutation • FLT3 mutation • MCL1 overexpression

Xospata (gilteritinib) • MEN1703

11d

Allogeneic hematopoietic stem cell transplantation could overcome the poor prognosis of DNMT3AmutNPM1mutFLT3-ITDmut in acute myeloid leukemia: real-world multicenter analysis in China. (PubMed, Front Med)

To our knowledge, this work is the largest study to explore the up-to-date undefined role of allo-HSCT in patients with triple-mutated AML. Our real-world data suggest that allo-HSCT could overcome the poor prognosis of DNMT3AmutNPM1mutFLT3-ITDmut in AML.

11 days ago

Journal • Real-world evidence • Real-world

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1)

FLT3-ITD mutation • NPM1 mutation • FLT3‐ITD + DNMT3A mutation

12d

The Role of FLT3-ITD Mutation, PI3K/AKT Pathway, and Leukemia Stem Cells in D3A7 Induction therapy - the Outcomes of Adult Indonesian Patients with Acute Myeloid Leukemia. (PubMed, Acta Med Acad)

This study presents the important role of FLT3-ITD mutation via its downstream signaling (PI3K/AKT) in the outcome of D3A7 induction therapy. The FLT3-ITD mutation plays an important role in the 12-month survival of AML patients after D3A7 therapy. However, the outcome of D3A7 therapy and FLT3-ITD mutation were not associated with leukemia stem cells.

12 days ago

Journal

FLT3 (Fms-related tyrosine kinase 3)

FLT3-ITD mutation

cytarabine • daunorubicin

13d

The Clinical Impact of NPM1 Mutations and the Effect of Concurrent Mutations in Acute Myeloid Leukemia: Unraveling the Prognostic Significance. (PubMed, Health Sci Rep)

The evaluation of NPM1 mut and co-mutation has consistently demonstrated remarkable prognostic significance in AML, suggesting the potential for improved response rates, extended disease-free periods, and OS. Our findings provide valuable insights for understanding molecular leukemogenesis in AML-NK patients and will aid in clinical diagnosis, prognostic implications, and the development of targeted therapy strategies for Syrian AML patients.

13 days ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1)

FLT3-ITD mutation • NPM1 mutation • DNMT3A mutation + FLT3-ITD mutation • FLT3‐ITD + DNMT3A mutation

15d

Survival impact of hypoxia-inducible factor-1 alpha (HIF-1α) in Nucleophosmin1 mutated acute myeloid leukemia. (PubMed, Ann Hematol)

In summary, high HIF-1α expression is potentially a baseline prognostic biomarker for poor RFS and cytarabine resistance in NPM1+FLT3-ITD- AML. Further studies with the large number of patients are warranted.

15 days ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • HIF1A (Hypoxia inducible factor 1, alpha subunit)

FLT3-ITD mutation • NPM1 mutation • HIF1A overexpression • HIF1A expression

cytarabine

20d

Extramedullary immunoprivileged sites as a niche for residual and relapsed FLT3-ITD mutated AML: an unmet clinical need. (PubMed, Leuk Lymphoma)

No abstract available

20 days ago

Journal

FLT3 (Fms-related tyrosine kinase 3)

FLT3-ITD mutation

21d

Identification of inhibitors targeting the FLT3-ITD mutation through 4D-QSAR, in vitro, and in silico. (PubMed, Eur J Med Chem)

Additionally, molecular docking and molecular dynamics (MD) simulations showed that Compounds A1, B2, and C2 had similar binding modes to that of Gilteritinib with more stable affinities. Overall, these results demonstrated that Compounds A1, B2, and C2 were promising inhibitors for targeting AML with FLT3-ITD mutation.

21 days ago

Preclinical • Journal

FLT3 (Fms-related tyrosine kinase 3)

FLT3-ITD mutation

Xospata (gilteritinib)

22d

Development of Potent and Selective Inhibitors of Methylenetetrahydrofolate Dehydrogenase 2 for Targeting Acute Myeloid Leukemia: SAR, Structural Insights, and Biological Characterization. (PubMed, J Med Chem)

Furthermore, synergistic effects were observed when combining potential compounds with Alimta. Compound 16e emerged as a leading candidate, demonstrating superior inhibition and selectivity for MTHFD2, favorable pharmacokinetics, and potent antitumor efficacy in MOLM-14 xenograft models.

22 days ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • MTHFD2 (Methylenetetrahydrofolate Dehydrogenase (NADP+ Dependent) 2)

FLT3-ITD mutation

pemetrexed

22d

Sorafenib as maintenance therapy in FLT3+ acute myeloid leukemia post allogeneic transplantation: a case report. (PubMed, Anticancer Drugs)

Sorafenib is increasingly significant after allo-HSCT maintenance, offering a promising option for high-risk AML cases. In this case, the patient achieved long-term remission with minimal side effects.

22 days ago

Journal

FLT3 (Fms-related tyrosine kinase 3)

FLT3-ITD mutation

sorafenib

Molecular measurable residual disease monitoring and transplant indications in NPM1 mutated acute myeloid leukemia. (PubMed, Bone Marrow Transplant)

In this review, we evaluate the prognostic role of MRD monitoring in NPM1 mutated AML and its use as a predictive biomarker to refine risk stratification and inform decision making regarding treatment. We explore the impact of pre-HCT MRD positivity on post-HCT outcomes in this AML subset, and how HCT-related factors such as conditioning intensity may influence this risk.

1 month ago

Review • Journal

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)

FLT3-ITD mutation • NPM1 mutation

Homoharringtonine Added to Venetoclax and Azacitidine Improves Outcome and Mitigates Genetic Impact in Relapsed/Refractory AML: A Multi-center Cohort Study. (PubMed, Clin Cancer Res)

Our findings suggest the addition of HHT to VA might enhance response and mitigate the negative impact of certain genetic patterns in RR-AML while being well tolerated.

1 month ago

Journal

KRAS (KRAS proto-oncogene GTPase) • FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • TET2 (Tet Methylcytosine Dioxygenase 2)

KRAS mutation • FLT3-ITD mutation • FLT3 mutation • DNMT3A mutation • TET2 mutation

Venclexta (venetoclax) • azacitidine • Synribo (omacetaxine mepesuccinate)

OXPHOS mediators in acute myeloid leukemia patients: Prognostic biomarkers and therapeutic targets for personalized medicine. (PubMed, World J Surg Oncol)

This study identifies NDUFA6 and SDHA as novel companion prognostic biomarkers which might present a rational strategy for personalized therapy of AML patients.

1 month ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NPM1 (Nucleophosmin 1) • SRSF2 (Serine and arginine rich splicing factor 2) • GPX4 (Glutathione Peroxidase 4) • CYB5A (Cytochrome B5 Type A) • CPT1A (Carnitine Palmitoyltransferase 1A) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)

FLT3-ITD mutation • IDH1 mutation • NPM1 mutation • SRSF2 mutation • NPM1 expression • NPM1 mutation + SRSF2 mutation

Evaluation of drug-drug interactions of a novel potent FLT3 inhibitor SKLB1028 in healthy subjects. (PubMed, Clin Transl Sci)

Based on the preclinical characterization of SKLB1028 metabolism, three drug-drug interaction clinical studies were performed to investigate the effects of itraconazole, rifampin (CYP3A4 inhibitor and inducer, respectively), and gemfibrozil (CYP2C8 inhibitor) on the metabolism of SKLB1028. Co-administration with rifampin reduced the AUC of SKLB1028 by ~30%, while the Cmax did not change significantly. All treatments were well tolerated in all three studies.

1 month ago

Journal

FLT3 (Fms-related tyrosine kinase 3)

FLT3-ITD mutation

itraconazole • rifampicin • ruserontinib (SKLB-1028)

Target-Capture Next-Generation Sequencing (NGS) for Use in Molecular-Based Research of Myeloid Measurable Residual Disease (MRD) (AMP 2024)

Target-capture NGS provides the opportunity to evaluate many genes in a single assay. Suitability for MRD requires highly uniform and sensitive target enrichment. Our study demonstrated reliable and accurate detection of variants down to 0.05% VAF, providing researchers with the capability to use capture-based NGS for myeloid MRD monitoring.

1 month ago

Next-generation sequencing

FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • JAK2 (Janus kinase 2)

FLT3-ITD mutation • NPM1 mutation • FLT3 D835Y • FLT3 D835 • IDH2 R172K • KIT D816V • IDH1 R132C • JAK2 V617F • IDH1 R132 • IDH2 R172

SureSeq™ Myeloid MRD Panel

DNA and RNA NGS for Myeloid Neoplasms Using Oncomine Myeloid Assay GX v2 on GeneXus: An Assessment of Clinical Utility (AMP 2024)

This DNA- and RNA-based 80-gene panel has proven to be a powerful tool for genomic profiling of myeloid neoplasms. The results were provided to hematopathologists/oncologists in timely fashion with the critical information for diagnosis confirmation, and disease classification, as well as assessment of patient response to treatment.

1 month ago

Clinical • Next-generation sequencing

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • DDX41 (DEAD-Box Helicase 41) • CALR (Calreticulin) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

FLT3-ITD mutation • NPM1 mutation • U2AF1 mutation • CEBPA mutation • JAK2 V617F

Oncomine Myeloid Assay GX

Characteristics and Outcome of FLT3-ITD-Positive Acute Myeloid Leukemia. (PubMed, Clin Lab)

Allo-HSCT immediately following complete remission could improve outcomes for young adults diagnosed with FLT3-ITD-positive AML. However, we found no statistical difference in the overall response rate (ORR) and clinical outcome between sorafenib combined with chemotherapy and chemotherapy alone.

1 month ago

Retrospective data • Journal

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)

FLT3-ITD mutation • NPM1 mutation

sorafenib

Safety and Efficacy of Quizartinib in Children and Young Adults With Acute Myeloid Leukemia (AML), a Cancer of the Blood (clinicaltrials.gov)

P1/2, N=65, Active, not recruiting, Daiichi Sankyo | Recruiting --> Active, not recruiting

1 month ago

Enrollment closed • Combination therapy

FLT3 (Fms-related tyrosine kinase 3)

FLT3-ITD mutation

cytarabine • etoposide IV • Vanflyta (quizartinib) • fludarabine IV

Measurable residual mutated IDH1 before allogeneic transplant for acute myeloid leukemia. (PubMed, Bone Marrow Transplant)

For patients with IDH1 mutated AML co-mutated with NPM1 and/or FLT3-ITD, only detection of persistent mutated NPM1 and/or FLT3-ITD was associated with significantly higher rates of relapse (p = 0.01). These data, from the largest study to date, do not support the detection of IDH1 mutation in CR1 blood prior to alloHCT as evidence of AML MRD for increased post-transplant relapse risk.

1 month ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NPM1 (Nucleophosmin 1)

FLT3-ITD mutation • IDH1 mutation • FLT3 mutation • NPM1 mutation

Prognostic Significance of Low Copy Number FLT3 and NPM1 mrd As Detected By Ultra-Sensitive Next Generation Sequencing (ASH 2024)

While most patients with "low-level" MRD positivity later have negative MRD testing, there is a subset of patients that go on to develop "high-level" MRD and are thus at increased risk of relapse. These data suggest that MRD positivity below the clinically-validated limit of detection is challenging to interpret, and that longitudinal MRD monitoring is vital for disease surveillance.

1 month ago

Next-generation sequencing

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)

FLT3-ITD mutation • NPM1 mutation • FLT3‐ITD + NPM1 mutation

FLT3 ITD MRD Assay • NPM1 Mutation Assay

Measurable Residual Mutated NPM1 before Allogeneic Transplant for Acute Myeloid Leukemia (ASH 2024)

NPM1 MRD positive patients receiving nonmyeloablative conditioning or reduced-intensity conditioning (RIC) without melphalan (mel) had increased risk of relapse or death compared to patients receiving myeloablative conditioning or RIC with mel, regardless of FLT3-ITD co-mutational status (3yrs : relapse 87% vs 55%, P=0.006; OS 15% vs 42%, P=0.013). Conclusions : In patients with NPM1 mutated AML from the Pre-MEASURE study, we show that detection of residual NPM1 variants in pre-transplant blood during CR1 using a highly sensitive DNA-based assay is associated in a dose-dependent manner with a significantly increased risk of relapse and death after allo-HCT, which can be mitigated in part by conditioning regimen. In patients co-mutated for both FLT3-ITD and NPM1 at diagnosis, NPM1 should be prioritized as a target for NGS-MRD if only one test is available.

1 month ago

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)

FLT3-ITD mutation • FLT3 mutation • NPM1 mutation

FLT3 ITD MRD Assay • NPM1 Mutation Assay

melphalan

Prognostic Role of NGS-Based MRD Assessment in FLT3-TKD Mutated Patients with Acute Myeloid Leukemia (ASH 2024)

Only two patients in the MRD negative group received the FLT3 inhibitor midostaurin combined with chemotherapy...NGS-MRD was not prognostic in this cohort of FLT3-TKD mutated AML patients. Shared first authors : Isabell Arnhardt, Christian M Vonk Shared senior authorship : Michael Heuser, Peter J.M. Valk

1 month ago

Clinical • Next-generation sequencing

FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2)

FLT3-ITD mutation • NPM1 mutation • ASXL1 mutation • TET2 mutation • SF3B1 mutation • FLT3-TKD mutation

TruSight Myeloid Sequencing Panel

Rydapt (midostaurin)

PRDM16 Induces Methylation of FLT3 to Promote FLT3-ITD Signaling and Leukemia Progression. (PubMed, Cancer Res)

Altogether, these results suggest that PRDM16 boosts oncogenic FLT3 signaling in leukemic cells by prompting FLT3-ITD methylation. Therefore, PRDM16 may serve as a therapeutic target for AML.

1 month ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • PRDM16 (PR/SET Domain 16)

FLT3-ITD mutation • FLT3 wild-type • FLT3 expression • FLT3-ITD expression

2ms

Analysis of Morphologic Classification System for Acute Promyelocytic Leukemia and Its Correlation with Laboratory Tests and FLT3-ITD Mutation (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)

The newly established morphologic classification system in this study can objectively characterize different types of APL blast cells, which helps to better assess the intra- and inter-individual heterogeneity of APL blast cells, and further use in accurately analyzing the correlation of morphological phenotypes with biological properties of APL.

2 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3)

FLT3-ITD mutation • FLT3 mutation

2ms

Exploring the Prevalence and Prognostic Impact of Wilms Tumor 1 Exon 7 Mutation Status with Combinations of FLT3-ITD and NPM1 Mutations as Potential Molecular Biomarkers in Acute Myeloid Leukemia Patients with Normal Cytogenetics. (PubMed, Asian Pac J Cancer Prev)

This study found a significant association between patient survival outcomes and NPM1 mutation status, as well as the combined FLT3-ITD and NPM1 status. Profiling both NPM1 and FLT3-ITD mutations at the time of diagnosis serves as a robust prognostic marker in AML treatment. WT1 mutation status did not show a significant association with patient outcomes. Larger population studies may provide more relevant insights.

2 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • WT1 (WT1 Transcription Factor)

FLT3-ITD mutation • NPM1 mutation • WT1 mutation • FLT3‐ITD + NPM1 mutation • FLT3-ITD mutation + WT1 mutation • FLT3‐ITD + WT1 mutation

2ms

The prognostic significance of genetics in acute myeloid leukemia under venetoclax-based treatment. (PubMed, Ann Hematol)

Its combination with HMA or low-dose cytarabine (LDAC) has been shown to enhance the response rates and prolong the survival outcomes of older or unfit patients with AML. Additionally, we examined the response rates and survival outcomes of CBF-AML when treated with a VEN-based regimen. Moving forward, it is imperative that risk stratification for LIT becomes more nuanced to better align with the requirements of personalized diagnosis and treatment strategies.

2 months ago

Review • Journal • IO biomarker

FLT3 (Fms-related tyrosine kinase 3) • BCL2 (B-cell CLL/lymphoma 2) • NPM1 (Nucleophosmin 1)

FLT3-ITD mutation • NPM1 mutation

Venclexta (venetoclax) • cytarabine

2ms

Measurable residual mutated IDH2 before allogeneic transplant for acute myeloid leukemia. (PubMed, Bone Marrow Transplant)

Patients testing negative for IDH2m prior to transplant had low relapse-related death, regardless of conditioning intensity. Post-transplant relapse rates for those with persistently detectable IDH2m in pre-transplant remission were lower after the FDA approval of enasidenib in August 2017.

2 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1)

FLT3-ITD mutation • IDH2 mutation • NPM1 mutation

Idhifa (enasidenib)

2ms

Quizartinib with donor lymphocyte infusion for post-transplant relapse of FLT3-ITD-positive acute myeloid leukemia. (PubMed, Int J Hematol)

The patient achieved hematological CR on day 163 and remained in molecular CR 3 years after allo-HCT without adverse effects. Quizartinib combined with DLI may be a feasible treatment for early relapse of FLT3-ITD-positive AML after allo-HCT, even with concurrent DNMT3A and NPM1 mutations.

2 months ago

Journal • Post-transplantation

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1)

FLT3-ITD mutation • NPM1 mutation • DNMT3A mutation • DNMT3A mutation + NPM1 mutation • DNMT3A R882

Vanflyta (quizartinib)

2ms

Identification of furo[2,3-d]pyrimidin-4-ylsulfanyl-1,3,4-thiadiazole derivatives as novel FLT3-ITD inhibitors. (PubMed, Eur J Med Chem)

Notably, compound 49 demonstrated cytotoxic effects in Ba/F3 cells expressing FLT3-ITD or FLT3-ITD-F691L mutant, exceeding the potency of both sorafenib and quizartinib. The study suggests that substituted furo[2,3-d]pyrimidines could be useful additions to the growing field of FLT3-targeted therapy for AML. These compounds have the potential to serve as novel FLT3-ITD inhibitors and may offer insights for developing future therapeutic strategies in AML.

2 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3)

FLT3-ITD mutation • FLT3 F691L • FLT3 expression • FLT3-ITD expression • FLT3-ITD mutation + FLT3 F691L

sorafenib • Vanflyta (quizartinib)

2ms

Anti-leukemic effects of Vernonia amygdalina extract. (PubMed, Braz J Biol)

The potential of alkaloid fractions on MOLM-13 cells was indicated by the robust cytotoxic effect of the alkaloid fractions, which resulted in over 50% cell mortality at 30 µg/ml. Our results suggest that VAE-96 may be a beneficial agent for the prevention and treatment of AML with FLT3-ITD mutation.

2 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3)

FLT3-ITD mutation • FLT3 expression

2ms

CLAG±DAC regimen in the treatment of refractory/relapsed acute myeloid leukemia (PubMed, Zhonghua Xue Ye Xue Za Zhi)

Objective: To investigate the efficacy and prognosis of CLAG±DAC (Clofarabine, Cytarabine, G-CSF±Decitabine) chemotherapy in patients with relapsed/refractory acute myeloid leukemia (R/R AML) . The remission rate was relatively higher in patients with R/R AML combined with FLT3-ITD mutation by applying the DAC+CLAG regimen (OR=10.84, 95%CI 1.48-288.50, P=0.04) . The CLAG±DAC regimen is considered effective in patients with R/R AML, whereas decitabine combined with the CLAG regimen is more suitable for patients with R/R AML combined with FLT3-ITD mutation.

2 months ago

Retrospective data • Journal

FLT3 (Fms-related tyrosine kinase 3) • DNMT3A (DNA methyltransferase 1)

FLT3-ITD mutation • DNMT3A mutation

cytarabine • decitabine • clofarabine

2ms

A Study of ASP2215 in Combination With Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia. (clinicaltrials.gov)

P1/2, N=97, Completed, Astellas Pharma Inc | Active, not recruiting --> Completed

2 months ago

Trial completion • Combination therapy

FLT3 (Fms-related tyrosine kinase 3)

FLT3-ITD mutation

cytarabine • Xospata (gilteritinib) • idarubicin hydrochloride

2ms

Tarlock K, Gerbing RB, Ries RE, et al. Prognostic impact of cooccurring mutations in FLT3-ITD pediatric acute myeloid leukemia. Blood Adv. 2024;8(9):2094-2103. (PubMed, Blood Adv)

No abstract available

2 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3)

FLT3-ITD mutation • FLT3 mutation

2ms

Targeting rapid TKI-induced AXL upregulation overcomes adaptive ERK reactivation and exerts antileukemic effects in FLT3/ITD acute myeloid leukemia. (PubMed, Mol Oncol)

Finally, we observed that TKI-induced AXL upregulation occurs in patient samples, and combined inhibition of both AXL and FLT3 increased efficacy in our in vivo models. Taken together, these data suggest that AXL plays a role in adaptive resistance in FLT3/ITD AML and that combined AXL and FLT3 inhibition might improve FLT3/ITD AML patient outcomes.

2 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • AXL (AXL Receptor Tyrosine Kinase)

FLT3-ITD mutation

2ms

Clinical features and long-term outcomes of pediatric patients with de novo acute myeloid leukemia in China with or without specific gene abnormalities: a cohort study of patients treated with BCH-AML 2005. (PubMed, Hematology)

Not achieving complete remission after induction 2 was found to be an independent prognostic factor for OS and EFS. These findings indicate that genetic abnormalities could be considered stratification factors, predict patient outcomes, and imply the application of targeted therapy.

2 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • NUP214 (Nucleoporin 214) • CBFB (Core-Binding Factor Subunit Beta 2) • DEK (DEK Proto-Oncogene)

FLT3-ITD mutation • KIT mutation • KMT2A rearrangement • MLL rearrangement • DEK-NUP214 rearrangement

3ms

Pathogenesis and treatment of acute myeloid leukemia with FLT3 mutations (PubMed, Rinsho Ketsueki)

In Japan, alongside monotherapy with gilteritinib or quizartinib for relapsed/refractory patients, combination of quizartinib with intensive chemotherapy was approved in 2023 for untreated FLT3-ITD mutation-positive AML. Thus, FLT3 mutations are utilized not only as a prognostic factor in AML but also as a target for treatment and for response assessment. Furthermore, the development of new treatment strategies involving FLT3 inhibitors is highly anticipated to improve clinical outcomes for patients with FLT3 mutation-positive AML.

3 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3)

FLT3-ITD mutation • FLT3 mutation

Xospata (gilteritinib) • Vanflyta (quizartinib)

3ms

Measurable Residual Disease Monitoring in AML With FLT3-ITD Treated With Intensive Chemotherapy Plus Midostaurin. (PubMed, Blood Adv)

NGS-based FLT3-ITD MRD monitoring allows for the identification of patients at high risk of relapse and death following intensive chemotherapy plus midostaurin. Using NGS-based technology, FLT3-ITD emerges as a novel, clinically highly relevant target for MRD monitoring.

3 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)

FLT3-ITD mutation • NPM1 mutation

Rydapt (midostaurin)

3ms

Quizartinib: a new hope in acute myeloid leukemia, an applied comprehensive review. (PubMed, Future Oncol)

It has shown promise in clinical studies since 2013 due to its excellent oral absorption and potent activity on FLT3. This review explores Quizartinib's mechanism of action, efficacy in monotherapy or combination with chemotherapy, drug interactions, adverse events, resistance mechanisms and future research directions.

3 months ago

Review • Journal

FLT3 (Fms-related tyrosine kinase 3)

FLT3-ITD mutation • FLT3 mutation

Vanflyta (quizartinib)