News - FLT3 mutation - LARVOL VERI

11h

SUCLG1 restricts POLRMT succinylation to enhance mitochondrial biogenesis and leukemia progression. (PubMed, EMBO J)

Importantly, succinyl-CoA level and POLRMT succinylation are downregulated in FLT3-mutated clinical leukemia samples, linking enhanced mitobiogenesis to cancer progression. Together, SUCLG1 connects succinyl-CoA with POLRMT succinylation to modulate mitochondrial function and cancer development.

11 hours ago

Journal

FLT3 (Fms-related tyrosine kinase 3)

FLT3 mutation

Cost-effectiveness of adding quizartinib to induction chemotherapy for patients with FLT3-mutant acute myeloid leukemia. (PubMed, Leuk Lymphoma)

With an incremental gain of 0.84 quality-adjusted life years (QALYs) with quizartinib + 7 + 3 induction vs. 7 + 3 alone, the incremental cost-effectiveness ratio for the addition of quizartinib to standard 7 + 3 was $344,039/QALY. Only an 87% reduction in the average wholesale price of quizartinib or omitting quizartinib continuation therapy after completion of consolidation therapy and allogeneic hematopoietic cell transplant would make quizartinib a cost-effective option.

1 day ago

Journal • HEOR • Cost-effectiveness • Cost effectiveness

FLT3 (Fms-related tyrosine kinase 3)

FLT3-ITD mutation • FLT3 mutation

Vanflyta (quizartinib)

KB-LANRA- 1001: A Study to Evaluate Lanraplenib (LANRA) in Combination With Gilteritinib in Participants With FLT3-mutated Relapsed or Refractory Acute Myeloid Leukemia (AML) (clinicaltrials.gov)

P1/2, N=24, Terminated, Kronos Bio | Trial completion date: Oct 2024 --> Apr 2024 | Active, not recruiting --> Terminated; Sponsor decision

2 days ago

Trial completion date • Trial termination • Combination therapy

FLT3 (Fms-related tyrosine kinase 3)

FLT3 mutation

Xospata (gilteritinib) • lanraplenib (GS-9876)

Current knowledge about FLT3 gene mutations, exploring the isoforms, and protein importance in AML. (PubMed, Mol Biol Rep)

This review also discusses the development of molecular treatments targeting FLT3, including first-generation and next-generation tyrosine kinase inhibitors, highlighting the challenges of resistance that often arise during therapy. The final chapter describes FLT3 protein domain rearrangements and their relevance to AML pathogenesis.

4 days ago

Review • Journal

FLT3 (Fms-related tyrosine kinase 3)

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

Narazaciclib, a novel multi-kinase inhibitor with potent activity against CSF1R, FLT3 and CDK6, shows strong anti-AML activity in defined preclinical models. (PubMed, Sci Rep)

Significant leukemia load reductions in bone marrow, where disease originated, were also achieved in both responders (AM7577/AM8096), implicating that HX301 might be a potentially more effective therapy than those only affecting peripheral leukemic cells. Altogether, narazaciclib can potentially be a candidate treatment for a subset of AML with CSF1Rhi and/or mutant FLT3-ITD variants, particularly second generation FLT3 inhibitor resistant variants.

4 days ago

Preclinical • Journal

FLT3 (Fms-related tyrosine kinase 3) • CDK6 (Cyclin-dependent kinase 6) • CSF1R (Colony stimulating factor 1 receptor)

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

narazaciclib (HX301)

High remission rates and transition to allogeneic transplant in older patients with newly diagnosed FLT-3 mutated acute myelogenous leukemia with midostaurin plus intensive chemotherapy. (PubMed, Leuk Lymphoma)

No abstract available

6 days ago

Journal

FLT3 (Fms-related tyrosine kinase 3)

FLT3 mutation

Rydapt (midostaurin)

Inhibition of NRF2 signaling overcomes acquired resistance to arsenic trioxide in FLT3-mutated Acute Myeloid Leukemia. (PubMed, Ann Hematol)

We have previously reported that primary cells from FLT3-ITD mutated AML patients were sensitive to ATO in-vitro compared to other non-M3 AML and molecular/pharmacological inhibition of NF-E2 related factor 2 (NRF2), a master regulator of antioxidant response improved the chemosensitivity to ATO and daunorubicin even in non FLT3-ITD mutated cell lines and primary samples. We examined the effects of molecular/pharmacological suppression of NRF2 on acquired ATO resistance in the FLT3-ITD mutant AML cell line (MV4-11-ATO-R). Digoxin decreased leukemic burden and prolonged survival in MV4-11 ATO-R xenograft mice. We establish that altering NRF2 expression may reverse acquired ATO resistance in FLT3-ITD AML.

7 days ago

Preclinical • Journal

FLT3 (Fms-related tyrosine kinase 3) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2) • GLI2 (GLI Family Zinc Finger 2)

FLT3-ITD mutation • FLT3 mutation

daunorubicin • arsenic trioxide

A practical algorithm for acute myeloid leukaemia diagnosis following the updated 2022 classifications. (PubMed, Crit Rev Oncol Hematol)

We propose a practical algorithm for the speedy diagnosis of AML. Future classifications may need to incorporate gene mutation combinations to enable personalised treatment regimens in the management of patients with AML.

9 days ago

Review • Journal

FLT3 (Fms-related tyrosine kinase 3)

FLT3 mutation

11d

FLAG/FLAG-Ida Regimen in Secondary and Relapsed/Refractory Acute Myeloid Leukemia-Even in the Era of New Treatment Modalities Still a Significant Player. (PubMed, J Clin Med)

The aim of the study was to assess the efficacy and toxicity of fludarabine, cytarabine, and granulocyte-colony stimulation factor (FLAG) with or without idarubicin (-Ida) and to discuss novel therapies in this setting. Among the variables, including age, FLT3 mutation status, European LeukemiaNet (ELN) 2022 classification risk, FLAG vs. FLAG-Ida, and aHSCT, a multivariate analysis revealed that only aHSCT significantly influenced overall survival. (4) FLAG(-Ida) chemotherapy remains an effective salvage chemotherapy for patients with r/r and secondary AML with a plan of proceeding to aHSCT.

11 days ago

Journal

FLT3 (Fms-related tyrosine kinase 3)

FLT3 mutation

cytarabine • idarubicin hydrochloride • fludarabine IV

13d

FLT-3 mutation maybe an inferior predictor of daratumumab therapy in acute myeloid leukemia patients relapsed after allogeneic stem cell transplantation. (PubMed, Int J Lab Hematol)

No abstract available

13 days ago

Journal

FLT3 (Fms-related tyrosine kinase 3)

FLT3 mutation

Darzalex (daratumumab)

13d

Alpha/Beta T Cell and CD19+ B Cell Depletion in Allogeneic Stem Cell Transplantation in Patients With Malignant Diseases (clinicaltrials.gov)

P2, N=20, Recruiting, University of Florida | Not yet recruiting --> Recruiting

13 days ago

Enrollment open

FLT3 (Fms-related tyrosine kinase 3)

FLT3 mutation • CBL mutation • Chr t(9;11)

13d

Management of isocitrate dehydrogenase 1/2 mutated acute myeloid leukemia. (PubMed, Leukemia)

The emergence of these novel agents in AML offers patients a new modality of therapy, and shifts treatment paradigms toward individualized medicine. In this review, we outline the role of IDH mutations in malignant transformation, focus in on a novel group of targeted therapeutic agents directed toward IDH1- and IDH2-mutant AML, and explore their impact on prognosis in patients with AML.

13 days ago

Review • Journal

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

IDH2 mutation • FLT3 mutation

14d

Gemtuzumab ozogamicin plus midostaurin in combination with standard '7 + 3' induction therapy in newly diagnosed AML: Results from the SAL-MODULE phase I study. (PubMed, Br J Haematol)

Three dose levels of midostaurin and one to three sequential doses of 3 mg/m2 GO in combination with '7 + 3' induction were evaluated. Based on safety findings in 12 patients, our results show that 3 mg/m2 GO on Days 1 + 4 and 100 mg midostaurin on Days 8-21 can be safely combined with IC in newly diagnosed AML.

14 days ago

P1 data • Journal • Combination therapy

FLT3 (Fms-related tyrosine kinase 3)

FLT3 mutation

Rydapt (midostaurin) • Mylotarg (gemtuzumab ozogamicin)

15d

Pemigatinib After Chemotherapy for the Treatment of Newly Diagnosed Acute Myeloid Leukemia (clinicaltrials.gov)

P1, N=32, Recruiting, OHSU Knight Cancer Institute | Trial completion date: Aug 2024 --> Feb 2026 | Trial primary completion date: Feb 2024 --> Aug 2025

15 days ago

Trial completion date • Trial primary completion date

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • MECOM (MDS1 And EVI1 Complex Locus) • NUP214 (Nucleoporin 214) • GATA2 (GATA Binding Protein 2) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • DEK (DEK Proto-Oncogene) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

TP53 mutation • FLT3 mutation • RUNX1 mutation • ASXL1 mutation • EZH2 mutation • MLL rearrangement • SRSF2 mutation • U2AF1 mutation • BCOR mutation • Chr del(5q) • STAG2 mutation • FLT3 wild-type • Chr t(9;11) • ZRSR2 mutation

cytarabine • Pemazyre (pemigatinib) • daunorubicin • Starasid (cytarabine ocfosfate)

15d

NKX101-101: NKX101, Intravenous Allogeneic CAR NK Cells, in Adults With AML or MDS (clinicaltrials.gov)

P1, N=61, Active, not recruiting, Nkarta Inc. | Recruiting --> Active, not recruiting | N=90 --> 61

15 days ago

Enrollment closed • Enrollment change

FLT3 (Fms-related tyrosine kinase 3)

FLT3 mutation

cytarabine • cyclophosphamide • decitabine • fludarabine IV • NKX101

17d

Causes and risk factors for early death in adult patients with acute promyelocytic leukemia: a real-life experience. (PubMed, Hematol Transfus Cell Ther)

ED remains a substantial challenge in APL, especially in real-world settings with hemorrhage and infection being the leading causes. ECOG status and WBC count emerged as independent risk factors, while age and platelet count lacked a 30-day prognostic correlation. Evaluating prognostic enhancement tools in controlled trials and real-life settings is pivotal to improving APL outcomes.

17 days ago

Journal

FLT3 (Fms-related tyrosine kinase 3)

FLT3 mutation

18d

Sweet syndrome induced by FLT3 inhibitors: case report and literature review. (PubMed, Hematology)

The FLT3 inhibitor gilteritinib was administered for reinduction therapy after failure of chemotherapy with a combination of venetoclax, decitabine, aclarubicin, cytarabine and granulocyte colony-stimulating factor. Similar cases of Sweet syndrome following FLT3 inhibitor therapy for acute myeloid leukemia were reviewed. Attention should be given to this rare complication when FLT3 inhibitors are used for acute myeloid leukemia therapy, and appropriate treatments need to be administered in a timely manner.

18 days ago

Review • Journal

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

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

Venclexta (venetoclax) • cytarabine • Xospata (gilteritinib) • decitabine • aclarubicin

18d

Day-21 bone marrow findings incorrectly designate residual leukaemia in FLT3-mutated acute myeloid leukaemia treated with intensive induction plus midostaurin: a morphology-focused study. (PubMed, Pathology)

In summary, based on morphology alone, D21-BM assessment following 7+3 intensive induction plus midostaurin for FLT3-AML incorrectly designates RL in some patients; thus correlating with associated flow and molecular results is essential before concluding RL following first induction. Where remission status is unclear, repeat D28-BMs should be performed.

18 days ago

Journal

FLT3 (Fms-related tyrosine kinase 3)

FLT3 mutation

Rydapt (midostaurin)

Leukemic mutation FLT3-ITD is retained in dendritic cells and disrupts their homeostasis leading to expanded Th17 frequency. (PubMed, Front Immunol)

Together, our data suggests that FLT3-ITD+ leukemia-associated cDCs polarize CD4+ T cells into Th17 subsets, a population that has been shown to be negatively associated with survival in solid tumor contexts. This illustrates the complex tumor microenvironment of AML and highlights the need for further investigation into the effects of FLT3-ITD mutations on DC phenotypes and their downstream effects on Th polarization.

1 month ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • CD4 (CD4 Molecule) • CDK1 (Cyclin-dependent kinase 1)

FLT3-ITD mutation • FLT3 mutation

A phase 1 study of the irreversible FLT3 inhibitor FF-10101 in relapsed or refractory acute myeloid leukemia. (PubMed, Blood Adv)

Among 40 response-evaluable participants, the composite complete response rate was 10%, and the overall response rate (including partial responses) was 12.5%, including patients who had progressed on gilteritinib. The recommended phase 2 dose (RP2D) was 75 mg BID. FF-10101 potentially represents a next-generation advance in the management of FLT3-mutated AML.

1 month ago

P1 data • Journal

FLT3 (Fms-related tyrosine kinase 3)

FLT3 mutation

Xospata (gilteritinib) • FF-10101

NCI-2019-04959: Azacitidine, Venetoclax, and Gilteritinib in Treating Patients With Recurrent/Refractory FLT3-Mutated Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, or High-Risk Myelodysplastic Syndrome/Myeloproliferative Neoplasm (clinicaltrials.gov)

P1/2, N=55, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=42 --> 55

1 month ago

Enrollment closed • Enrollment change

FLT3 (Fms-related tyrosine kinase 3)

FLT3-ITD mutation • FLT3 mutation • FLT3 D835

Venclexta (venetoclax) • Xospata (gilteritinib)

Gilteritinib as Post-Transplant Maintenance for Acute Myeloid Leukemia With Internal Tandem Duplication Mutation of FLT3. (PubMed, J Clin Oncol)

Although the overall improvement in RFS was not statistically significant, RFS was higher for participants with detectable FLT3-ITD MRD pre- or post-HCT who received gilteritinib treatment. To our knowledge, these data are among the first to support the effectiveness of MRD-based post-HCT therapy.

1 month ago

Journal • Post-transplantation

FLT3 (Fms-related tyrosine kinase 3)

FLT3-ITD mutation • FLT3 mutation

Xospata (gilteritinib)

Testing the Addition of an Anti-cancer Drug, SNDX-5613, to the Standard Chemotherapy Treatment (Daunorubicin and Cytarabine) for Newly Diagnosed Patients With Acute Myeloid Leukemia That Has Changes in NPM1 or MLL/KMT2A Gene (clinicaltrials.gov)

P1, N=28, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Trial completion date: Feb 2024 --> Dec 2027 | Initiation date: Feb 2024 --> Nov 2024 | Trial primary completion date: Feb 2024 --> Dec 2027

1 month ago

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Combination therapy

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)

FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • MLL rearrangement • FLT3 wild-type • MLL mutation

daunorubicin • revumenib (SNDX-5613) • Starasid (cytarabine ocfosfate)

FLT3 Mutated Acute Myeloid Leukemia after CD19 CAR-t Cells. (PubMed, Mediterr J Hematol Infect Dis)

No abstract available

1 month ago

Journal • CAR T-Cell Therapy • IO biomarker

FLT3 (Fms-related tyrosine kinase 3)

FLT3 mutation

2ms

NCI-2018-01813: Quizartinib With Azacitidine or Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov)

P1/2, N=73, Completed, M.D. Anderson Cancer Center | N=200 --> 73

2 months ago

Enrollment change

FLT3 (Fms-related tyrosine kinase 3)

FLT3 mutation

cytarabine • azacitidine • Vanflyta (quizartinib) • Starasid (cytarabine ocfosfate)

2ms

A Safety and Efficacy Study of CC-90009 Combinations in Subjects With Acute Myeloid Leukemia (clinicaltrials.gov)

P1, N=22, Active, not recruiting, Celgene | Phase classification: P1/2 --> P1

2 months ago

Phase classification

FLT3 (Fms-related tyrosine kinase 3)

FLT3 mutation

Venclexta (venetoclax) • Xospata (gilteritinib) • azacitidine • eragidomide (CC-90009)

2ms

Therapeutic biomarkers in acute myeloid leukemia: functional and genomic approaches. (PubMed, Front Oncol)

However, functional approach requires robust standardization for multiple variables such as functional parameters, time of drug exposure and drug concentration for making in vitro predictions. In this review, we first summarize genomic and functional therapeutic biomarkers adopted for AML therapy, followed by challenges associated with these approaches, and finally, the future strategies to enhance the implementation of precision medicine.

2 months ago

Review • Journal

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

FLT3 mutation

2ms

Clinical Significance of Genetic and Molecular Changes in Primary Myeloid Sarcoma (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)

The genetic and molecular abnormalities of primary MS can be detected by FISH and NGS techniques. FLT3-ITD, RUNX1, ASXL1 or TP53 mutation indicates a worse prognosis, but further clinical studies are needed to confirm it.

2 months ago

Journal

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • RARA (Retinoic Acid Receptor Alpha) • PML (Promyelocytic Leukemia) • CD34 (CD34 molecule) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • CD68 (CD68 Molecule) • CBFB (Core-Binding Factor Subunit Beta 2) • CD99 (CD99 Molecule) • SPN (Sialophorin)

TP53 mutation • FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • KIT mutation • ASXL1 mutation • CEBPA mutation

2ms

CD117 expression predicted FLT3 mutation in T-cell acute lymphoblastic leukemia. (PubMed, EJHaem)

No abstract available

2 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • KIT (KIT proto-oncogene, receptor tyrosine kinase)

FLT3 mutation • KIT expression

2ms

Discovery of FLT3-targeting PROTACs with potent antiproliferative activity against acute myeloid leukemia cells harboring FLT3 mutations. (PubMed, Eur J Med Chem)

Comparative molecular dynamic (MD) simulation studies further elucidated the underlying mechanism of compound 35 to stabilize the dynamic ensemble of the FLT3-compound 35-cereblon (CRBN) ternary complex. Taken together, compound 35 could serve as a lead molecule for developing FLT3 degraders against AML.

2 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • CRBN (Cereblon)

FLT3 mutation

2ms

FRIDA: Study of Iadademstat and Gilteritinib in Patients With R/R AML With FMS-like Tyrosine Kinase Mutation (FLT3 Mut+) (clinicaltrials.gov)

P1, N=50, Recruiting, Oryzon Genomics S.A. | Trial primary completion date: Jan 2024 --> Jan 2025

2 months ago

Trial primary completion date

FLT3 (Fms-related tyrosine kinase 3)

FLT3 mutation • FLT3 D835 • FLT3 I836

Xospata (gilteritinib) • iadademstat (ORY-1001)

2ms

UM171 Expanded Cord Blood In Patients With High-Risk Acute Leukemia/Myelodysplasia (clinicaltrials.gov)

P2, N=30, Active, not recruiting, Ciusss de L'Est de l'Île de Montréal | Recruiting --> Active, not recruiting | N=20 --> 30 | Trial completion date: Dec 2023 --> Oct 2027 | Trial primary completion date: Dec 2023 --> Oct 2024

2 months ago

Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • JAK2 (Janus kinase 2) • HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • CD34 (CD34 molecule)

TP53 mutation • FLT3 mutation • RAS mutation • JAK2 mutation

cyclophosphamide • ECT-001-CB

2ms

Treatment Patterns and FLT3 Mutation Testing Among Patients with Acute Myeloid Leukemia in China: A Retrospective Observational Study. (PubMed, Ther Clin Risk Manag)

Study findings showed that there was a lack of routine testing for FLT3 mutations at first diagnosis of R/R AML, and initial treatment decisions did not differ by FLT3 mutation status. Given the clinical burden of FLT3MUT, likelihood of FLT3 status changes, and emerging FLT3 inhibitors, further routine FLT3 screening is needed to optimize treatment of R/R AML.

2 months ago

Observational data • Retrospective data • Journal

FLT3 (Fms-related tyrosine kinase 3)

FLT3 mutation • FLT3 positive

2ms

Clinical and genetic characteristics predict outcomes of acute myeloid leukemia patients with FLT3 mutations receiving venetoclax-based therapy. (PubMed, Cancer Med)

FLT3 mutations may influence response to VEN-based therapy in R/R AML patients but not in ND AML patients. Furthermore, clinical and genetic characteristics could predict outcomes of FLT3mut patients receiving VEN-based therapy.

2 months ago

Journal

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

FLT3 mutation • NPM1 mutation • DNMT3A mutation • FLT3 wild-type

Venclexta (venetoclax)

2ms

NCI-2018-01789: Quizartinib, Decitabine, and Venetoclax in Treating Participants With Untreated or Relapsed Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome (clinicaltrials.gov)

P1/2, N=72, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting

2 months ago

Enrollment open

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3)

TP53 mutation • FLT3-ITD mutation • FLT3 mutation • TP53 deletion

Venclexta (venetoclax) • Vanflyta (quizartinib) • decitabine

3ms

Crenolanib and Intensive Chemotherapy in Adults With Newly Diagnosed FLT3-Mutated AML. (PubMed, J Clin Oncol)

Crenolanib plus intensive chemotherapy in adults with newly diagnosed FLT3-mutant AML results in high rate of deep responses and long-term survival with acceptable toxicity. A randomized trial of crenolanib versus midostaurin plus chemotherapy in younger patients is ongoing.

3 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3)

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

cytarabine • Rydapt (midostaurin) • crenolanib (ARO-002) • daunorubicin • idarubicin hydrochloride

3ms

OGILAR: Study Investigating the Efficacy and Safety of the Addition of Oral-azacitidine to Salvage Treatment by Gilteritinib in Subjects ≥18 Years of Age With Relapsed/Refractory FLT3-mutated Acute Myeloid Leukemia (clinicaltrials.gov)

P2, N=33, Recruiting, French Innovative Leukemia Organisation | Not yet recruiting --> Recruiting

3 months ago

Enrollment open

FLT3 (Fms-related tyrosine kinase 3)

FLT3 mutation • FLT3 D835 • FLT3 I836

Xospata (gilteritinib) • Onureg (azacitidine oral)

3ms

AMLM26/T1 INTERCEPT: A multi-arm trial for patients with acute myeloid leukaemia investigating new treatments which target early relapse and changes in disease characteristics - Gilteritinib+ Venetoclax (ACTRN12624000082505)

P1/2, N=60, Not yet recruiting, Australasian Leukaemia and Lymphoma Group

3 months ago

New P1/2 trial

FLT3 (Fms-related tyrosine kinase 3)

FLT3 mutation • CBL mutation

Venclexta (venetoclax) • Xospata (gilteritinib)

3ms

Quantification of midostaurin in plasma and serum by stable isotope dilution liquid chromatography-tandem mass spectrometry: Application to a cohort of patients with acute myeloid leukemia. (PubMed, Eur J Haematol)

In a real-life cohort of AML patients, interindividual variability in midostaurin serum concentrations was high, highlighting issues concerning optimal drug dosing in AML patients. A personalized dosage approach may maximize the safety of midostaurin. Prospective studies and standardization of analytical methods to support such an approach are needed.

3 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3)

FLT3 mutation

cytarabine • Rydapt (midostaurin) • daunorubicin

3ms

Prognostic Impact of Co-occurring Mutations in FLT3-ITD Pediatric Acute Myeloid Leukemia. (PubMed, Blood Adv)

However, ITDpos/NUP98::NSD1 patients continued to have poor outcomes with intensified therapy, including sorafenib. Co-occurring mutational profile in ITDpos AML has significant prognostic impacts is critical to determining risk stratification and therapeutic allocation for ITDpos patients.

3 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • WT1 (WT1 Transcription Factor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1)

FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • CEBPA mutation • WT1 mutation

sorafenib

3ms

Gilteritinib in combination with venetoclax, low-dose cytarabine and actinomycin D for relapsed or refractory FLT3-mutated acute myeloid leukaemia. (PubMed, Br J Haematol)

The median overall survival and relapse-free survival after G-ACTIVE were 32 and 12.9 months respectively. The Day 60 mortality rate was 15%.

3 months ago

Journal • Combination therapy

FLT3 (Fms-related tyrosine kinase 3)

FLT3 mutation

Venclexta (venetoclax) • cytarabine • Xospata (gilteritinib) • dactinomycin

3ms

BRCC36 associates with FLT3-ITD to regulate its protein stability and intracellular signaling in acute myeloid leukemia. (PubMed, Cancer Sci)

Thiolutin efficiently affected leukemia cell lines expressing FLT3-ITD cell viability and exhibited mutual synergies with quizartinib, a standard clinical medicine for AML. Furthermore, mutation of the lysine at 609 of ITD led to significant suppression of K63 polyubiquitination and decreased its stability, suggesting that K609 is a critical site for K63 ubiquitination specifically recognized by BRCC36. These data indicate that BRCC36 is a specific regulator for FLT3-ITD, which may shed light on developing a novel therapeutic approach for AML.

3 months ago

Journal • BRCA Biomarker

FLT3 (Fms-related tyrosine kinase 3) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

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

Vanflyta (quizartinib)