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Association details:
| Biomarker: | FLT3 mutation |
|---|---|
| Cancer: | Acute Myelogenous Leukemia |
| Drug: | sorafenib (Multi-tyrosine kinase inhibitor, pan-RAF inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
Investigating the role of targeted therapy Sorafenib - the Fms-like tyrosine kinase 3 (FLT3) inhibitor, in combination with intensive chemotherapy, for previously untreated adult patients with Acute Myeloid Leukaemia (AML) with FLT3 mutations. A Phase II randomised placebo-controlled multi-centre study
Excerpt:
...Logistic and Cox regression will be used for additional analyses involving the evaluation of additional prognostic factors., To determine other measures of efficacy in untreated adult AML with FLT3 ITD mutation administered the FLT3 inhibitor Sorafenib compared to a control group: CR, CRi, CRp, CRc, 2y-EFS, 2y-PFS and 2y-OS., To investigate exploratory markers of clinical benefit: MRD by flow cytometry and WT1., To identify biomarkers of response e.g. plasma FLT3 ligand levels, FLT3 mRNA transcript levels, quantitative FLT3 mutant allelic load, the presence of non-juxtamembrane FLT3-ITD lesions, the ability of plasma Sorafenib to inhibit FLT3 phosphorylation ex vivo, pharmacokinetic aspects of administered Sorafenib and modifying effects of other AML mutations e.g. NPM, CEBPA, IDH, Ras and others as they become available....
Trial ID:
Source:
Title:
Sorafenib Tosylate and Chemotherapy in Treating Older Patients With Acute Myeloid Leukemia
Excerpt:
...- FLT3 mutation (ITD or point mutation) determined by the OSU Molecular Reference Laboratory, per CALGB 20202...
Trial ID:
More C2 evidence
Source:
Title:
Using Sorafenib as a Salvage Treatment for Relapsed or Refractory Acute Myeloid Leukemia Carrying FLT3-ITD
Excerpt:
...Patients with AML carrying Flt3 mutation; AND,...
Trial ID:
Less C2 evidence
Source:
Title:
154 - FLT3 Inhibitor Maintenance after154 Allogeneic Stem Cell Transplantation in FLT3-Mutated Acute Myeloid Leukemia (AML) Patients
Published date:
12/16/2022
Excerpt:
We performed a single center, retrospective cohort study and analyzed patients who had FLT3+ AML…FLT3i maintenance therapy, including Midostaurin, Sorafenib, and Gilteritinib, was started…when adjusted for the conditioning regimen and donor status, the differences were statistically significant with improvement in OS for patients on FLT3i maintenance (HR 0.42, 95% CI 0.18 to 0.95, p = 0.04).
Source:
Title:
Outcomes in Molecular Subgroups and Resistance Patterns with Ten-Day Decitabine and Venetoclax (DEC10-VEN) in Acute Myeloid Leukemia
Published date:
11/06/2019
Excerpt:
Among 15 pts with FLT3-ITD/TKD, 8 pts received sorafenib...Among ND FLT3mut AML pts (n=7), the CR/CRi rate was 100%.
DOI:
https://doi.org/10.1182/blood-2019-128547
Trial ID:
Source:
Title:
Combinatorial targeting of XPO1 and FLT3 exerts synergistic anti-leukemia effects through induction of differentiation and apoptosis in FLT3-mutated acute myeloid leukemias: from concept to clinical trial
Excerpt:
In an ongoing phase IB clinical trial the selinexor/sorafenib combination induced complete/partial remissions in six of 14 patients with refractory acute myeloid leukemia, who had received a median of three prior therapies...These results provide pre-clinical and clinical evidence for an effective combinatorial treatment strategy targeting XPO1 and FLT3 in FLT3- mutated acute myeloid leukemias.
Secondary therapy:
selinexor
DOI:
10.3324/haematol.2017.185082
Trial ID:
Source:
Title:
Mutant FLT3: a direct target of sorafenib in acute myelogenous leukemia
Excerpt:
Sorafenib reduced the percentage of leukemia blasts in the peripheral blood and the bone marrow of AML patients with FLT3-ITD (median percentages before and after sorafenib: 81% vs 7.5% [P = .016] and 75.5% vs 34% [P = .05], respectively) but not in patients without this mutation.
DOI:
10.1093/jnci/djm328
Source:
Title:
Compassionate use of sorafenib in FLT3-ITD–positive acute myeloid leukemia: sustained regression before and after allogeneic stem cell transplantation
Excerpt:
...sorafenib for the treatment of relapsed or refractory FLT3-ITD-positive AML. Sorafenib induced clinically meaningful and very rapid responses in all 6 patients treated either before (n = 2), after (n = 3), or both before and after (n = 1) allogeneic stem cell transplantation (allo-SCT).
DOI:
https://doi.org/10.1182/blood-2009-03-208298
Source:
Title:
Potent Activity of Ponatinib (AP24534) in Models of FLT3-Driven Acute Myeloid Leukemia and Other Hematologic Malignancies
Excerpt:
...potent inhibitory activity of sorafenib and sunitinib was observed against FLT3 (IC50s of 4 and 12 nmol/L, respectively) and PDGFRα (0.5 and 3 nmol/L), neither compound exhibited high potency against KIT (59 and 56 nmol/L) or FGFR1 (>100 and >100 nmol/L; ref. Fig. 2B and Table 1).
DOI:
10.1158/1535-7163.MCT-10-1044
