^
Contact us  to learn more about
our Premium Content:  News alerts, weekly reports and conference planners
BIOMARKER:

FLT3-TKD mutation

i
Other names: FLT3, Fms Related Tyrosine Kinase 3, Receptor-Type Tyrosine-Protein Kinase FLT3, Stem Cell Tyrosine Kinase 1, Fms-Like Tyrosine Kinase 3, CD135, FLK-2, STK1, Growth Factor Receptor Tyrosine Kinase Type III, Fetal Liver Kinase 2
Entrez ID:
Related tests:
26d
Comparing Cytarabine + Daunorubicin Therapy Versus Cytarabine + Daunorubicin + Venetoclax Versus Venetoclax + Azacitidine in Younger Patients With Intermediate Risk AML (A MyeloMATCH Treatment Trial) (clinicaltrials.gov)
P2, N=153, Not yet recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025
Trial completion date • Trial primary completion date
|
TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • RARA (Retinoic Acid Receptor Alpha) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • PML (Promyelocytic Leukemia) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
|
TP53 mutation • FLT3-ITD mutation • NPM1 mutation • RUNX1 mutation • ASXL1 mutation • FLT3-TKD mutation • CEBPA mutation
|
Venclexta (venetoclax) • cytarabine • azacitidine • daunorubicin • Starasid (cytarabine ocfosfate)
2ms
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.
Journal
|
FLT3 (Fms-related tyrosine kinase 3)
|
FLT3-ITD mutation • FLT3 mutation • FLT3-TKD mutation
|
cytarabine • Rydapt (midostaurin) • crenolanib (ARO-002) • daunorubicin • idarubicin hydrochloride
4ms
Preclinical characterization of danatinib as a novel FLT3 inhibitor with excellent efficacy against resistant acute myeloid leukemia. (PubMed, Biomed Pharmacother)
In vivo safety evaluations performed on the granulopoiesis of transgenic myeloperoxidase (MPO) zebrafish and mice models proved danatinib to have an acceptable safety profile. Danatinib holds promise as a new and improved FLT3 inhibitor for the treatment of AML, offering long-lasting remissions and improved overall survival rates.
Preclinical • Journal
|
FLT3 (Fms-related tyrosine kinase 3) • MPO (Myeloperoxidase)
|
FLT3-ITD mutation • FLT3-TKD mutation
4ms
Efficacy and safety of BHA regimen for FLT3-mutated relapsed/refractory acute myeloid leukemia: a prospective, multi-center, single-arm clinical study (ChiCTR2300074321)
P1, N=65, Not yet recruiting, The Second Affiliated Hospital of Dalian Medical University; The Second Affiliated Hospital of Dalian Medical University
New P1 trial
|
FLT3 (Fms-related tyrosine kinase 3)
|
FLT3-ITD mutation • FLT3 mutation • FLT3-TKD mutation
|
cytarabine • bortezomib • Synribo (omacetaxine mepesuccinate)
4ms
Real-World Data for FLT3-Mutated Acute Myeloid Leukemia Patients Treated in Resource-Constrained Settings (ASH 2023)
our results show that the frequency of FLT3-ITD mutations and their association with worse prognosis was similar to those described in high-income countries previously to the Introduction of TKI as the standard of care. Therefore, allogeneic HSCT remains a valid consolidation strategy for FLT3-mutated patients. However, less than half of the patients for whom HSCT was indicated were actually transplanted.
Clinical • Real-world evidence • Real-world
|
FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)
|
FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • FLT3-TKD mutation • FLT3 wild-type
5ms
Enrollment open
|
FLT3 (Fms-related tyrosine kinase 3) • CD33 (CD33 Molecule)
|
FLT3-ITD mutation • FLT3-TKD mutation • CD33 positive
|
cytarabine • Xospata (gilteritinib) • Mylotarg (gemtuzumab ozogamicin)
5ms
Real-World Outcomes Using Front-Line Midostaurine in Combination with Intensive Chemotherapy for Patients Aged ≥ 60 Years Old with FLT3 Mutated Acute Myeloid Leukemia (ASH 2023)
Regarding the intensive chemotherapy schedule in induction, 162 (84.8%) patients were treated with idarubicin-based regimens, 18 (9.4%) with daunorubicin-based regimens, and 8 (4.2%) with CPX-351... This real-life study suggests that the addition of midostaurine to intensive chemotherapy regimens in elderly patients could result in acceptable CRc, OS and EFS. In order to establish the benefit of midostaurin, we will compare these results with a historical control cohort.
Clinical • Combination therapy • Real-world evidence • Real-world
|
FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)
|
FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • FLT3-TKD mutation
|
Rydapt (midostaurin) • Vyxeos (cytarabine/daunorubicin liposomal formulation) • idarubicin hydrochloride
5ms
A Phase I/II Study of Combination of ASTX727, Gilteritinib and Venetoclax in Patients with Relapsed/Refractory FLT3­ Mutated Acute Myeloid Leukemia (AML) (ASH 2023)
However, 80mg of GILT was selected for the phase II portion of this study based on the more favorable safety/efficacy profile and better count recovery observed in a parallel study of azacitidine combined with VEN and GILT in AML. Conclusion In this poor-risk population of pts with R/R FLT3-mutated AML or MDS/CMML, many of whom received prior HMA + VEN, the combination of ASTX727, VEN, and GILT was active, with an ORR of 53%. The trial continues to enroll to the R/R cohort, and is now open for patients with newly diagnosed FLT3-mutated AML who are unsuitable for intensive chemotherapy.
Clinical • P1/2 data
|
FLT3 (Fms-related tyrosine kinase 3)
|
FLT3-ITD mutation • FLT3 mutation • FLT3-TKD mutation
|
Venclexta (venetoclax) • Xospata (gilteritinib) • azacitidine • Inqovi (decitabine/cedazuridine)
5ms
Gemtuzumab Ozogamicin for Patients with Newly Diagnosed CD33 Positive Acute Myeloid Leukemia: Results from a French Retrospective Observational Study (ASH 2023)
During the first induction treatment, most patients (98.1%; n=105/107) received GO in association with other agents, most commonly cytarabine and daunorubicin (60.0%; n=63/105)... GO was predominantly administered according to its indication. Response rates were similar to those reported in the pivotal ALFA-0701 study. Median OS was longer in this study than in ALFA-0701 (49.8 vs 27.5 months), although median RFS and EFS were reduced.
Observational data • Retrospective data
|
CD33 (CD33 Molecule)
|
FLT3-TKD mutation • CD33 positive
|
Mylotarg (gemtuzumab ozogamicin) • daunorubicin • Vyxeos (cytarabine/daunorubicin liposomal formulation)
5ms
T-Cell Receptor-Engineered T Cells Targeting FLT3-D835 Mutation-Derived Neoantigens in Acute Myeloid Leukemia (ASH 2023)
Taken together, we present novel neoantigens with promise as immunotherapy targets for AML and other hematologic malignancies with FLT3-D835 mutations. Future studies will evaluate the efficacy of Neo-D835H-specific TCR-engineered T-cell-based immunotherapy in vivo in patient-derived xenograft murine model and TCR-based therapeutic approaches targeting other FLT3-TKD mutations.
IO biomarker
|
FLT3 (Fms-related tyrosine kinase 3) • CD8 (cluster of differentiation 8) • HLA-A (Major Histocompatibility Complex, Class I, A) • IFNG (Interferon, gamma) • TRB (T Cell Receptor Beta Locus)
|
FLT3 mutation • FLT3-TKD mutation • FLT3 D835Y • FLT3 D835 • HLA-A*02:01 • HLA-A*02 • FLT3 D835H
7ms
Effectiveness of chemotherapy using bortezomib combined with homoharringtonine and cytarabine in refractory or relapsed acute myeloid leukemia: a phase II, multicenter, prospective clinical trial. (PubMed, Front Oncol)
The higher CR/CRi rate will give a clue to determine a potentialeffectiveness of BHA for AML patients carrying FLT3 mutation in a further investigation. https://www.chictr.org.cn/, identifier ChiCTR2000029841.
P2 data • Journal
|
FLT3 (Fms-related tyrosine kinase 3)
|
FLT3-ITD mutation • FLT3 mutation • FLT3-TKD mutation
|
cytarabine • bortezomib • Synribo (omacetaxine mepesuccinate)
7ms
Investigating FLT3 Mutations In Acute Myeloid Leukemia: A Single‑Center Real‑World Data Study on Patient Outcomes and Treatment Strategies (SOHO 2023)
Patients treated with midostaurin faced a lower mortality risk than those administered sorafenib. This study underscores the significance of FLT3 mutations in AML, their influence on clinical outcomes, and the advantages of targeted therapies. Our findings stress the urgency for further investigation aimed at enhancing the prognosis for AML patients with FLT3 mutations.
Clinical • Real-world evidence • Real-world
|
FLT3 (Fms-related tyrosine kinase 3)
|
FLT3-ITD mutation • FLT3 mutation • FLT3-TKD mutation
|
sorafenib • Rydapt (midostaurin)
10ms
Enrollment closed • Combination therapy
|
FLT3 (Fms-related tyrosine kinase 3)
|
FLT3-ITD mutation • FLT3 mutation • FLT3-TKD mutation
|
Xospata (gilteritinib) • Rydapt (midostaurin)
11ms
EFFECTIVENESS OF REINDUCTION CHEMOTHERAPY USING BORTEZOMIB WITH HOMOHARRINGTONINE AND CYTARABINE IN REFRACTORY OR RELAPSED ACUTE MYELOID LEUKEMIA: A PHASE II, MULTICENTER, PROSPECTIVE CLINICAL TRIAL (EHA 2023)
BHA chemotherapy was safe and can serve as a reinduction therapy for R/R AML, particularly with FLT3 mutation. The higher response rate will pave a way for potential long-term survival in patients with R/R-AML, especially for those with FLT3 mutation. Clinical Trial registration: https://www.chictr.org.cn/ , identifier [ChiCTR2000029841].
Clinical • P2 data
|
FLT3 (Fms-related tyrosine kinase 3)
|
FLT3-ITD mutation • FLT3 mutation • FLT3-TKD mutation • FLT3 wild-type
|
cytarabine • bortezomib • Synribo (omacetaxine mepesuccinate)
11ms
TREATMENT WITH MIDOSTAURIN AND OTHER FLT3 TARGETING INHIBITORS IS ASSOCIATED WITH AN INCREASED RISK OF CARDIOVASCULAR ADVERSE EVENTS IN PATIENTS WITH FLT3 MUTATED AML WHO UNDERWENT ALLOGENEIC HCT (EHA 2023)
Of the 42 pts with FLT3 mutated AML, 34 pts (82%) received a FLT3i at some time during their treatment: 27 pts (79.4%) received mido, 24 pts (70.6%) another FLT3i (mainly sorafenib) and in 17 pts (50%) mido was followed by another FLT3i...Other known risk factors (i.e. age≥60 years, adverse or intermediate risk cytogenetics, obesity, preexisting cardiac comorbidity, female sex or cumulative daunorubicin equivalence dose) were not associated with a significantly higher number of CAEs... We here identified mido and/or FLT3i treatment as an independent risk factor for CAEs inpts undergoing HCT without higher NRM or impaired OS. The higher risk of rarely life-threatening CAE should not preclude administration of mido and/or FLT3i, even in pts with preexisting cardiac comorbidities, but close monitoring is warranted.
Clinical • Adverse events
|
FLT3 (Fms-related tyrosine kinase 3)
|
FLT3-ITD mutation • FLT3 mutation • FLT3-TKD mutation • FLT3 wild-type
|
sorafenib • Rydapt (midostaurin) • daunorubicin
11ms
GM-CLAG in Relapsed/Refractory FLT3-mutated AML (clinicaltrials.gov)
P1, N=0, Withdrawn, Ayman H Qasrawi | N=15 --> 0 | Not yet recruiting --> Withdrawn
Enrollment change • Trial withdrawal • Combination therapy
|
FLT3 (Fms-related tyrosine kinase 3)
|
FLT3-ITD mutation • FLT3-TKD mutation
|
cytarabine • Xospata (gilteritinib) • mitoxantrone • cladribine • Neupogen (filgrastim)
12ms
Vyxeos Plus Gilteritinib in Relapsed or Refractory, FLT3-Mutated AML (clinicaltrials.gov)
P1, N=22, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Suspended --> Recruiting
Enrollment open
|
FLT3 (Fms-related tyrosine kinase 3)
|
FLT3-ITD mutation • FLT3-TKD mutation
|
Xospata (gilteritinib) • Vyxeos (cytarabine/daunorubicin liposomal formulation)
12ms
De novo myeloid sarcoma mimicking gynecological tumors: a retrospective case series of eight patients. (PubMed, BMC Womens Health)
For patients with isolated MS, treatment by chemotherapy and surgery are radical procedure, and initial treatment using chemotherapy alone should be considered for MS with synchronous intramedullary AML. Poor response to chemotherapy, short interval to leukemia occurrence, and heavy tumor burden (> 10 cm) could indicate a poor prognosis for patients with MS.
Retrospective data • Journal
|
FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • JAK2 (Janus kinase 2) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • VIM (Vimentin) • CD99 (CD99 Molecule) • SPN (Sialophorin)
|
FLT3-TKD mutation
12ms
De novo monocytic-M5b AML with t(8;16) (p11.2; p13.3) KAT6A/CREBBP fusion and FLT3-TKD mutation complicated by chemotherapy-induced Takotsubo cardiomyopathy. (PubMed, BMJ Case Rep)
Our patient died in 6 months from the date of diagnosis. Although a rare occurrence, it has been discussed in literature to identify t(8;16) as a separate subtype of AML due to unique characteristics.
Journal
|
FLT3 (Fms-related tyrosine kinase 3) • CREBBP (CREB binding protein) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • KAT6A (Lysine Acetyltransferase 6A)
|
FLT3-TKD mutation • PTPRC expression • KAT6A-CREBBP fusion + FLT3-TKD mutation
almost1year
Enrollment open • Combination therapy
|
FLT3 (Fms-related tyrosine kinase 3)
|
FLT3-ITD mutation • FLT3 mutation • FLT3-TKD mutation
|
Xospata (gilteritinib) • Rydapt (midostaurin)
1year
Trial completion date • Trial primary completion date • Combination therapy
|
FLT3 (Fms-related tyrosine kinase 3)
|
FLT3-ITD mutation • FLT3 mutation • FLT3-TKD mutation
|
Xospata (gilteritinib) • Rydapt (midostaurin)
1year
Clinical Implications of the FLT3-ITD Allelic Ratio in Acute Myeloid Leukemia in the Context of an Allogeneic Stem Cell Transplantation. (PubMed, Cancers (Basel))
While co-mutated FLT3-TKD was associated with better outcomes, the MRD status at HSCT was the most significant factor for outcomes. While our data indicates that an allogeneic HSCT may mitigate the adverse effect of a high FLT3-ITD allelic ratio, comparative studies are needed to evaluate which FLT3-ITD mutated patients benefit from which consolidation strategy.
Journal
|
FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)
|
FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • FLT3-TKD mutation
1year
Trial completion date • Trial suspension • Combination therapy
|
FLT3 (Fms-related tyrosine kinase 3)
|
FLT3-ITD mutation • FLT3 mutation • FLT3-TKD mutation
|
Xospata (gilteritinib) • Rydapt (midostaurin)
over1year
FLT3 Gene Mutations in Acute Myeloid Leukemia Patients in Northeast Thailand. (PubMed, Med Sci Monit Basic Res)
CONCLUSIONS This study showed for the first time that FLT3-TKD mutation is common among northeast Thai AML patients. The data should prove useful for selecting efficacious targeted treatment plans for the patients.
Journal
|
FLT3 (Fms-related tyrosine kinase 3)
|
FLT3 mutation • FLT3-TKD mutation • FLT3 wild-type • FLT3 positive
over1year
Impact of FLT3 Inhibitor-Based Therapies on Outcomes of Acute Myeloid Leukemia (AML) Patients Receiving Allogenic Stem Cell Transplantation: A Retrospective Study (TCT-ASTCT-CIBMTR 2023)
Of the 29 patients who used maintenance therapy after HSCT, 18 (62%) received gilteritinib while 11 (38%) received midostaurin. Amongst our patients receiving FLT3 inhibitors for maintenance, OS at 24 months was 96.2% and RFS was 89.7%. OS and RFS for this group remained high at 36 months.
Retrospective data
|
FLT3 (Fms-related tyrosine kinase 3)
|
FLT3-ITD mutation • FLT3 mutation • FLT3-TKD mutation
|
Xospata (gilteritinib) • Rydapt (midostaurin)
over1year
Evaluating the clinical significance of FLT3 mutation status in Syrian newly diagnosed acute myeloid leukemia patients with normal karyotype. (PubMed, Heliyon)
Also, the frequency of FLT3-TKD mutation was low 2% and no compound between the two mutations was found, as individuals showed to carry the two mutations were not detected. These findings are likely useful for a better understanding of molecular leukemogenetic steps in AML-NK patients and may be beneficial for clinical relevance for risk grouping, study design and choice of therapy in Syrian population.
Journal
|
FLT3 (Fms-related tyrosine kinase 3)
|
FLT3-ITD mutation • FLT3 mutation • FLT3-TKD mutation
over1year
Gilteritinib activity in refractory or relapsed FLT3-mutated acute myeloid leukemia patients previously treated by intensive chemotherapy and midostaurin: a study from the French AML Intergroup ALFA/FILO. (PubMed, Leukemia)
Multivariate analyses for prognostic factors associated with OS identified female gender (HR 1.61), adverse cytogenetic risk (HR 2.52), and allogenic HSCT after gilteritinib (HR 0.13). Although these patients were more heavily pretreated, these real-world data reproduce the results of ADMIRAL and provide new insights into the course of patients previously treated by intensive chemotherapy and midostaurin and beyond the 2nd line of treatment who can benefit from treatment in an outpatient setting.
Journal
|
FLT3 (Fms-related tyrosine kinase 3)
|
FLT3 mutation • FLT3-TKD mutation
|
Xospata (gilteritinib) • Rydapt (midostaurin)
over1year
Vyxeos Plus Gilteritinib in Relapsed or Refractory, FLT3-Mutated AML (clinicaltrials.gov)
P1, N=22, Suspended, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Suspended
Trial suspension
|
FLT3 (Fms-related tyrosine kinase 3)
|
FLT3-ITD mutation • FLT3-TKD mutation
|
Xospata (gilteritinib) • Vyxeos (cytarabine/daunorubicin liposomal formulation)
over1year
Trial initiation date
|
TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • RARA (Retinoic Acid Receptor Alpha) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • PML (Promyelocytic Leukemia) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
|
TP53 mutation • FLT3-ITD mutation • NPM1 mutation • RUNX1 mutation • ASXL1 mutation • FLT3-TKD mutation • CEBPA mutation
|
Venclexta (venetoclax) • cytarabine • azacitidine • daunorubicin • Starasid (cytarabine ocfosfate)
over1year
Gilteritinib Activity in Refractory or Relapsed FLT3-Mutated Acute Myeloid Leukemia Patients Previously Treated By Intensive Chemotherapy and Midostaurin: A Study from the French AML Intergroup ALFA/Filo (ASH 2022)
Multivariate analyses disclosed female gender (HR 1.61, 95%CI 1.07-2.42, p=0.02), adverse cytogenetic risk (HR 2.52, 95%CI 1.24-5.13, p=0.01) and allo-HSCT after gilteritinib (HR 0.13, 95%CI 0.05-0.37, p<0.0001) as factors significantly and independently associated with OS. Conclusion Although patients in this study were more heavily pretreated, these real-world data reproduce ADMIRAL results and provide new insights in the outcome of patients previously treated by intensive chemotherapy and midostaurin and beyond the 2nd line of treatment.
Clinical
|
FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)
|
FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • FLT3-TKD mutation • FLT3 wild-type
|
Xospata (gilteritinib) • Rydapt (midostaurin)
over1year
A Phase I/II Study of Combination of ASTX727, Gilteritinib and Venetoclax in Patients with Relapsed/Refractory FLT3­ Mutated Acute Myeloid Leukemia (AML) and Frontline FLT3 Mutated AML Patients Unfit for Chemotherapy (ASH 2022)
Hydroxyurea or 1 dose of cytarabine up to 1000 mg was allowed in pts with proliferative disease to lower white blood count to ≤ 25 x 109/L before initiation of study therapy. The combination therapy with ASTX727, VEN, and gilteritinib appears to be effective and safe in R/R FLT3 mutated AML and HR-MDS. Myelosuppression was frequent but manageable. Continued accrual is anticipated to define the optimal triplet regimen in both R/R and newly diagnosed FLT3-mutated AML.
Clinical • P1/2 data
|
FLT3 (Fms-related tyrosine kinase 3) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1)
|
FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • DNMT3A mutation • FLT3-TKD mutation
|
Venclexta (venetoclax) • cytarabine • Xospata (gilteritinib) • Inqovi (decitabine/cedazuridine) • hydroxyurea
over1year
Updated Results from a Phase I/II Study of the Triplet Combination of Azacitidine, Venetoclax and Gilteritinib for Patients with FLT3-Mutated Acute Myeloid Leukemia (ASH 2022)
The combination of azacitidine, venetoclax and gilteritinib is effective in pts with FLT3-mutated AML. OS in the ND cohort compares favorably with historical expectations of FLT3-mutated AML treated with HMA plus venetoclax without a FLT3 inhibitor.
Clinical • P1/2 data
|
FLT3 (Fms-related tyrosine kinase 3)
|
FLT3-ITD mutation • FLT3 mutation • FLT3-TKD mutation • FLT3 positive
|
Venclexta (venetoclax) • Xospata (gilteritinib) • azacitidine
over1year
Intensive Therapy for NPM1 Mutant AML Patients: Negative Impact of FLT3-ITDhighbut Not FLT3-ITDlow and FLT3-TKD and Role of Transplant in Patients over 60 Years of Age (ASH 2022)
We included patients from January 2013 to August 19, 2021 from 7 centers with NPM1+ AML who received induction chemotherapy with an anthracycline and cytarabine... In our multicenter cohort of pts with NPM1+ AML, OS was significantly inferior in pts with ITDhigh v. FLT3neg, but not in ITDlow and TKD. Co-mutations in DNMT3A and TET2 adversely affected overall survival. Our data did not find a significant difference in OS in pts >60 with NPM1+/FLT3-ITDneg who were consolidated with chemotherapy versus SCT, though larger follow up studies are needed.
Clinical
|
FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • TET2 (Tet Methylcytosine Dioxygenase 2)
|
FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • DNMT3A mutation • TET2 mutation • FLT3-TKD mutation
|
cytarabine
over1year
Epag 2015 : A Phase II Randomized Placebo-Controlled Study to Assess the Impact on Outcome of Eltrombopag Administered to Elderly Patients with Acute Myeloid Leukemia Receiving Induction Chemotherapy. a French Innovative Leukemia Organization (FILO) Study (ASH 2022)
The induction chemotherapy regimen consisted of one cycle of daunorubicin 60 mg/m²/day (d), d1 to d3, cytarabine 100 mg/m²/d, CIV d1 to d7, lomustine 200 mg/m², orally d1...Pts then received 6 months of maintenance therapy alternating mercaptopurin and methotrexate. The addition of midostaurin in patients with FLT3-ITD or FLT3-TKD mutations was not allowed during induction...These differences are not statistically significant. Conclusion In older AML pts eligible for intensive treatment, adding eltrombopag to induction is feasible and safe, reduces significantly the need of platelet transfusions, yet did not impact survival in this study.
Clinical • P2 data
|
FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • NPM1 (Nucleophosmin 1)
|
FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • FLT3-TKD mutation • FLT3 mutation + NPM1 mutation
|
cytarabine • Rydapt (midostaurin) • methotrexate • daunorubicin • lomustine • Promacta (eltrombopag)
over1year
The Expression of mi-RNAs Involved in the Hematopoietic Niche Microenvironment in Newly Diagnosed AML Patients (ASH 2022)
The majority of patients (88.9%) received intensive treatment: DA-60 (daunorubicin 60mg/m2 + cytarabine 200mg/m2) regimen (50%), followed by DAC (DA-60 + cladribine 5mg/m2) (40%) and DA-90 (daunorubicin 90mg/m2 + cytarabine 100mg/m2) (10%). Azacitidine in standard dose was used as the low-intensity regimen...These data indicate that miR-199-5p may be a potential prognostic factor in AML patients. Larger studies are needed to confirm our observation.
Clinical
|
FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • MIR34A (MicroRNA 34a-5p) • MIR146A (MicroRNA 146a) • MIR199B (MicroRNA 199b) • MIR139 (MicroRNA 139) • MIR424 (MicroRNA 424) • MIR15A (MicroRNA 15a) • MIR181A1 (MicroRNA 181a-1) • MIR204 (MicroRNA 204) • MIR218 (MicroRNA 218)
|
FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • FLT3-TKD mutation • miR-424 expression
|
cytarabine • azacitidine • daunorubicin • cladribine
over1year
Real-World Outcomes and Cardiac Implications of FLT3 Inhibitors in Acute Myeloid Leukemia (ASH 2022)
FLT3 inhibitors are divided into first generation multi-kinase inhibitors (such as sorafenib, lestaurtinib, midostaurin) and next generation inhibitors (such as quizartinib, crenolanib, gilteritinib) or based on their specificity of FLT3 inhibition [type I inhibitors (midostaurin, gilteritinib) inhibit FLT3 ITD and TKD mutations whereas type II inhibitors (sorafenib, quizartinib) have only FLT3 ITD activity]. Type II FLT3 TKIs had worse cardiac safety profile in our cohort and an increased risk of cardiac toxicity, particularly in patients with prior reduced ejection fraction or A-fib. A careful cardiac history and management of predisposing conditions to serious cardiac events could help improve drug tolerance, morbidity, and mortality. Further studies are required to elucidate the precise mechanisms of increased incidence of cardiac arrythmias and ways to mitigate them.
Clinical • Real-world evidence
|
FLT3 (Fms-related tyrosine kinase 3)
|
FLT3-ITD mutation • FLT3 mutation • FLT3-TKD mutation
|
sorafenib • Xospata (gilteritinib) • Rydapt (midostaurin) • Vanflyta (quizartinib) • crenolanib (ARO-002) • lestaurtinib (CEP-701)
over1year
Dexaml-02 : A Phase II Study of Dexamethasone Added to Induction and Postremission Therapy in Older Patients with Newly Diagnosed AML. a French Innovative Leukemia Organization (FILO) Study (ASH 2022)
Induction chemotherapy regimen consisted in one cycle of idarubicin 8 mg/m²/day, D1 to D5, cytarabine 100 mg/m²/d, CIV D1 to D7, lomustine 200 mg/m²/d, orally at D1 and dexamethasone 10 mg/12h, IV, D1 to D3...The addition of midostaurin in patients with FLT3-ITD or FLT3-TKD mutations was allowed during induction, consolidation and maintenance...Conclusion In older AML patients who are eligible for intensive treatment, adding dexamethasone to induction and consolidation chemotherapy is feasible and associated with a high response rate after a single induction cycle and encouraging overall survival. A historical comparison with the patient population of the LAM-SA 2007 trial (Pigneux A, JCO 2018) will be presented during the meeting to highlight a potential signal of activity.
Clinical • P2 data
|
FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • SRSF2 (Serine and arginine rich splicing factor 2) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • NR3C1 (Nuclear Receptor Subfamily 3 Group C Member 1)
|
FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • FLT3-TKD mutation • SRSF2 mutation • FLT3 mutation + NPM1 mutation
|
cytarabine • Rydapt (midostaurin) • idarubicin hydrochloride • lomustine
over1year
Characterization of Survival Outcomes and Clinical and Molecular Modulators in Adult Patients with Core-Binding Factor Acute Myeloid Leukemia (CBF-AML) Treated with Hidac Consolidation: An Alliance Legacy Study (ASH 2022)
Moreover, there is persistent controversy about the optimal dose intensity of cytarabine consolidation, which complicates interpretation of correlative studies with respect to outcome associations...Support: U10CA180821, U10CA180882, U24CA196171; https://acknowledgments.alliancefound.org. Clinicaltrials.gov: NCT00048958(CALGB 8461), NCT00899223(CALGB 9665), NCT00900224(CALGB 20202) *co-senior authors
Clinical
|
KRAS (KRAS proto-oncogene GTPase) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • RUNX1 (RUNX Family Transcription Factor 1) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1)
|
KRAS mutation • NRAS mutation • KIT mutation • FLT3-TKD mutation • CBFB-MYH11 fusion
|
cytarabine