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Association details:
| Biomarker: | FLT3-ITD mutation |
|---|---|
| Cancer: | Acute Myelogenous Leukemia |
| Drug: | sorafenib (Multi-tyrosine kinase inhibitor, pan-RAF inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Excerpt:
Therapy for relapsed/refractory disease…Targeted therapy:…Therapy for AML with FLT3-ITD mutation...Hypomethylating agents (azacitidine or decitabine) + sorafenib...
Secondary therapy:
decitabine; azacitidine
Source:
Title:
Sorafenib maintenance after allogeneic haemopoietic stem-cell transplantation in patients with FLT3-ITD acute myeloid leukaemia: long-term follow-up of an open-label, multicentre, randomised, phase 3 trial
Published date:
07/03/2023
Excerpt:
With extended follow-up, sorafenib maintenance after transplantation is associated with improved long-term survival and reduced relapse rates compared with non-maintenance, further supporting this strategy as a standard of care for patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic HSCT.
DOI:
10.1016/S2352-3026(23)00117-5
Trial ID:
Source:
Title:
Sorafenib maintenance in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised phase 3 trial
Published date:
08/10/2020
Excerpt:
Sorafenib maintenance post-transplantation can reduce relapse and is well tolerated in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation. This strategy could be a suitable therapeutic option for patients with FLT3-ITD acute myeloid leukaemia.
DOI:
https://doi.org/10.1016/S1470-2045(20)30455-1
Trial ID:
Source:
Title:
Sorafenib Maintenance Therapy for Patients With AML After Allogeneic Stem Cell Transplant
Excerpt:
...- Subjects with AML with the FLT3-ITD mutation who have undergone allogeneic HSCT...
Trial ID:
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:
...FLT3-ITD mutation with an allelic mutant:wild-type ratio of = 0.05...
Trial ID:
More C2 evidence
Source:
Title:
Sorafenib in Treating Young Patients With Relapsed or Refractory Solid Tumors or Leukemia
Excerpt:
...- AML and FLT3-ITD mutation...
Trial ID:
Source:
Title:
Sorafenib to Treat FLT3-ITD AML
Excerpt:
...- FLT3-ITD mutation has been confirmed...
Trial ID:
Source:
Title:
Efficacy of Sorafenib Added to Standard Primary Therapy in Elderly Patients With Newly Diagnosed AML
Excerpt:
...Median Event Free Survival of AML patients with Flt3-ITD mutations`Median Event Free Survival of the patients in each of the four strata (Flt3 Non-ITD/NPM1 WT, Flt3 Non-ITD/NPM1 mut, Flt3 ITD/NPM1 WT, Flt3 ITD/NPM1 mut)`Median Overall Survival of AML patients with Flt3-ITD mutations`Median Overall Survival of all AML patients`Rate of Complete Remission in all AML patients`Rate of Molecular Remission in all AML patients`Toxicity`Evidence of Minimal Residual Disease in all AML patients`Development of Biomarkers indicating the course of disease...
Trial ID:
Source:
Title:
Sorafenib in the treatment of AML patients with FLT3-ITD mutation: a cohort study
Excerpt:
...FLT3-ITD mutation positive is confirmed; 3. ...
Trial ID:
Less C2 evidence
Source:
Title:
3589 Real World Experience of FLT3-Inhibitor Post-Transplant Maintenance with Sorafenib Demonstrating Superior Overall- and Relapse Free Survival Following Allogeneic Hematopoietic Stem Cell Transplantation in FLT3-ITD Mutated Acute Myeloid Leukemia
Published date:
11/02/2023
Excerpt:
We conducted a retrospective study including 69 patients who received an allogeneic HCT from 2019 to 2023 for AML with FLT3-ITD, of which 24 patients received Sorafenib as post-HCT maintenance therapy….we confirmed the 2-year RFS for patients who had a high FLT3-ITD and received Sorafenib maintenance was statistically significant when compared to no Sorafenib maintenance.
Source:
Title:
Phase II study of cladribine, idarubicin, and ara-C (CLIA) with or without sorafenib as initial therapy for patients with acute myeloid leukemia
Published date:
08/27/2023
Excerpt:
Among patients with FLT3-ITD mutated AML receiving CLIA+sorafenib, the CR + CRi rate was 95%, with 81% negative for MRD. With a median follow-up of 76 months, the 2- and 4-year OS of 57% and 50% compared to 20%, and 13% for ts-AML, respectively. Patients treated with CLIA+sorafenib had 2- and 5-year OS rates of 63% and 59%, respectively...The addition of sorafenib to CLIA in FLT3-ITD mutated AML resulted in high rates of durable remission and excellent long-term survival.
Secondary therapy:
CLIA
DOI:
10.1002/ajh.27054
Source:
Title:
SORAFENIB MAINTENANCE TAILORED TO FLT3-MUTATED AML AFTER ALLOGENEIC HCT IS HIGHLY FEASIBLE AND EFFECTIVE: A REAL-LIFE EXPERIENCE
Published date:
05/11/2023
Excerpt:
We hereby report data from 20 adult patients with FLT3-ITD+ AML receiving sorafenib after HCT….Sorafenib was overall well-tolerated….Eight patients completed the 2-years maintenance with sorafenib – median time of treatment 965 days(651 - 1431)….Overall, 16/18 patients with FLT3-ITD+ AML achieved stable long-lasting CR....Our real-life practice confirms that sorafenib maintenance therapy is well-tolerated and contributes to sustained long-lasting remissions of FLT3+ AML after allogeneic HCT.
Source:
Title:
Sorafenib in Combination With Standard Chemotherapy for Children With High Allelic Ratio FLT3/ITD+ Acute Myeloid Leukemia: A Report From the Children's Oncology Group Protocol AAML1031
Published date:
03/29/2022
Excerpt:
Sorafenib can be safely added to conventional AML chemotherapy and may improve outcomes in pediatric HAR FLT3/ITD+ AML.
Secondary therapy:
Chemotherapy
DOI:
10.1200/JCO.21.01612
Source:
Title:
Sorafenib or placebo in patients with newly diagnosed acute myeloid leukaemia: long-term follow-up of the randomized controlled SORAML trial
Published date:
02/18/2021
Excerpt:
A total number of 46/267 patients had FLT3-internal tandem duplication (ITD)-positive AML (17%) and 86/267 had NPM1-mutated AML (33%, Table 1)....The CR rate was 60% (81/134) in the sorafenib arm...In summary, the addition of sorafenib to standard intensive treatment led to a significant EFS and RFS prolongation after prolonged follow-up.
DOI:
10.1038/s41375-021-01148-x
Trial ID:
Source:
Title:
Phase 1 Study of combinatorial sorafenib, G-CSF, and plerixafor treatment in relapsed/refractory, FLT3-ITD-mutated acute myelogenous leukemia patients
Published date:
07/22/2020
Excerpt:
Twenty-eight patients with relapsed/refractory FLT3-ITD-mutated AML were enrolled from December 2010 to December 2013 at three dose levels of sorafenib (400, 600, and 800 mg twice daily) and G-CSF and plerixafor were administered every other day for seven doses starting on day one...In conclusion, the strategy of combined inhibition of FLT3 kinase and stromal adhesive interactions has promising activity in relapsed/refractory, FLT3-ITD-mutated AML.
Secondary therapy:
GCSF + plerixafor
DOI:
10.1002/ajh.25943
Source:
Title:
Sorafenib Maintenance After Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia With FLT3-Internal Tandem Duplication Mutation (SORMAIN)
Published date:
07/16/2020
Excerpt:
...83 adult patients with FLT3-ITD-positive AML in complete hematologic remission after HCT were randomly assigned to receive for 24 months either the multitargeted and FLT3-kinase inhibitor sorafenib (n = 43) or placebo (n = 40 placebo)....The 24-month RFS probability was 53.3% (95% CI, 0.36 to 0.68) with placebo versus 85.0% (95% CI, 0.70 to 0.93) with sorafenib (HR, 0.256; 95% CI, 0.10 to 0.65; log-rank P = .002)....Sorafenib maintenance therapy reduces the risk of relapse and death after HCT for FLT3-ITD-positive AML.
DOI:
10.1200/JCO.19.03345
Source:
Title:
Sorafenib in Combination with Standard Chemotherapy for Children with High Allelic Ratio FLT3/ITD+ AML Improves Event-Free Survival and Reduces Relapse Risk: A Report from the Children's Oncology Group Protocol AAML1031
Published date:
11/06/2019
Excerpt:
The improvement in EFS and RR observed with sorafenib was retained in those with wild-type nucleophosmin (NPM-) FLT3/ITD+ AML...Sorafenib improved rates of induction II CR as well as 3 year EFS and reduced RR from CR compared to historical controls.
DOI:
https://doi.org/10.1182/blood-2019-129557
Source:
Title:
Phase 2 study of azacytidine plus sorafenib in patients with acute myeloid leukemia and FLT-3 internal tandem duplication mutation
Excerpt:
The combination of AZA and sorafenib is effective for patients with relapsed AML and FLT-3-ITD.
Secondary therapy:
azacitidine
DOI:
https://dx.doi.org/10.1182%2Fblood-2013-01-480228
Trial ID:
Source:
Title:
Sorafenib treatment of FLT3-ITD+ acute myeloid leukemia: favorable initial outcome and mechanisms of subsequent nonresponsiveness associated with the emergence of a D835 mutation
Excerpt:
Thirteen patients with FLT3-ITD+ AML were treated with sorafenib. Twelve patients (92%) responded (CRi, n = 6; nCRi, n = 6), with the median time to best response at 27 (21-84) days.
DOI:
https://doi.org/10.1182/blood-2011-06-363960
Source:
Title:
Emergence of polyclonal FLT3 tyrosine kinase domain mutations during sequential therapy with sorafenib and sunitinib in FLT3-ITD-positive acute myeloid leukemia
Excerpt:
6 patients with relapsed/refractory FLT3-ITD-positive AML are summarized in Table 1. After treatment with sorafenib alone, or in combination with clofarabine and cytarabine, 4 patients achieved morphological complete remission (reduction of bone marrow blasts to < 5%).
Secondary therapy:
cytarabine + clofarabine
DOI:
https://dx.doi.org/10.1158%2F1078-0432.CCR-13-1323
Source:
Title:
Gilteritinib in relapsed FLT3-positive Acute Myeloid Leukemia after second allogeneic stem cell transplantation
Published date:
09/03/2020
Excerpt:
CONTRADICTING EVIDENCE: ...a 63-year-old patient with relapsed FLT3-ITD AML...Sorafenib was administered 3 months post-transplant as a maintenance therapy, but eventually the patient relapsed 4 months after sorafenib was terminated.
