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Association details:
| Biomarker: | FLT3-ITD mutation |
|---|---|
| Cancer: | Acute Myelogenous Leukemia |
| Drug: | Xospata (gilteritinib) (Multi-tyrosine kinase inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Excerpt:
Therapy for relapsed/refractory disease…Targeted therapy:…Therapy for AML with FLT3-ITD mutation...Gilteritinib (category 1)
Source:
Title:
GILTERITINIB VERSUS SALVAGE CHEMOTHERAPY FOR RELAPSED/REFRACTORY FLT3-MUTATED ACUTE MYELOID LEUKEMIA: A PHASE 3, RANDOMIZED, MULTICENTER, OPEN-LABEL TRIAL IN ASIA
Published date:
05/12/2022
Excerpt:
Baseline FLT3 mutations in the gilteritinib vs SC groups were: FLT3-ITD (91.4% vs 83.1%), FLT3-TKD (6.0% vs 11.9%), and both FLT3-ITD and FLT3-TKD (2.6% vs 5.1%). Median OS follow-up duration was 11.1 mo for gilteritinib and 6.9 mo for SC. Median OS was longer with gilteritinib (9.0 mo) vs SC (4.7 mo; HR 0.549 [95% CI: 0.379, 0.795]; P=0.00126); 1-year survival rate was 33.3% and 23.2%, respectively. OS benefit was seen with gilteritinib vs SC across most subgroups (Figure). Pts on gilteritinib had longer EFS than pts on SC (median EFS 2.8 vs 0.6 mo; HR 0.551 [95% CI: 0.395, 0.769]; P=0.00004). More pts had CR on gilteritinib (16.4%) vs SC (10.2%; P=0.17690); CRc rates were 50.0% and 20.3% (P<0.00001). Gilteritinib significantly prolonged OS and EFS vs SC in pts with R/R FLT3mut+ AML in Asia.
Trial ID:
Source:
Title:
Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML
Published date:
10/31/2019
Excerpt:
A consistent pattern of longer survival with gilteritinib than with chemotherapy was noted across multiple subgroups, including the high-intensity and low-intensity chemotherapy cohorts (Figure 2B) and the high FLT3 ITD allelic ratio subgroup (median overall survival, 7.1 vs. 4.3 months; hazard ratio for death, 0.49; 95% CI, 0.34 to 0.71)....gilteritinib therapy led to higher percentages of patients with response and longer survival than salvage chemotherapy among patients with relapsed or refractory FLT3-mutated AML.
Secondary therapy:
Chemotherapy
DOI:
10.1056/NEJMoa1902688
Trial ID:
Source:
Title:
A Study of ASP2215 (Gilteritinib), Administered as Maintenance Therapy Following Induction/Consolidation Therapy for Subjects With FMS-like Tyrosine Kinase 3 (FLT3/ITD) Acute Myeloid Leukemia (AML) in First Complete Remission
Excerpt:
......
Trial ID:
Source:
Title:
A Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-like Tyrosine Kinase (FLT3) Mutation
Excerpt:
...Participants can be enrolled from a local test result if they have any of the following FLT3 mutations: FLT3 internal tandem duplication (ITD), FLT3 tyrosine kinase domain (TKD)/D835 or FLT3- TKD/I836....
Trial ID:
More C2 evidence
Source:
Title:
A Study of ASP2215 in Combination With Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia.
Excerpt:
...- Subject is positive for FLT3-ITD and/or TKD mutation in bone marrow or whole blood as determined by the central lab....
Trial ID:
Source:
Title:
A Study of ASP2215 Versus Salvage Chemotherapy In Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FLT3 Mutation
Excerpt:
...Subjects can be enrolled from a local test result if the subjects have any of the following FLT3 mutations: FLT3-internal tandem duplication (ITD), FLT3-tyrosine kinase domain (TKD)/D835 or FLT3-TKD/I836....
Trial ID:
Source:
Title:
A study of Gilteritinib combined with chemotherapy to treat Children, Adolescents and Young Adults with Relapsed or Refractory Acute Myeloid Leukemia (AML) with a FLT3 gene mutation
Excerpt:
...Subject is positive for the FLT3/ITD mutation in bone marrow or blood as determined by the local institution.3. ...
Trial ID:
Source:
Title:
A Trial of the FMS-like Tyrosine Kinase 3 (FLT3) Inhibitor Gilteritinib Administered as Maintenance Therapy Following Allogeneic Transplant for Patients With FLT3/Internal Tandem Duplication (ITD) Acute Myeloid Leukemia (AML)
Excerpt:
......
Trial ID:
Less C2 evidence
Source:
Title:
GILTERITINIB MAINTENANCE AFTER ALLOGENEIC HEMATOPOIETIC STEMCELL TRANSPLANTATION FOR RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIAWITH FLT3–INTERNAL TANDEM DUPLICATION MUTATION
Published date:
05/11/2023
Excerpt:
Our results indicated that gilteritinib maintenance therapy reduced the risk of relapse after HSCT for patients with FLT3-ITD mutated r/r AML.
Source:
Title:
147 - Impact of FLT3 Inhibitor-Based Therapies on Outcomes of Acute Myeloid Leukemia (AML) Patients Receiving Allogenic Stem Cell Transplantation: A Retrospective Study
Published date:
12/16/2022
Excerpt:
All patients had an AML diagnosis with a FLT3 mutation…Of the 40 patients included in this study, 30 (75%) had the FLT3-ITD mutation, and 10 (25%) had the FLT3-TKD mutation….Post-HSCT maintenance, primarily with gilteritinib, resulted in improved OS and RFS in our patients. Amongst our patients receiving FLT3 inhibitors for maintenance, OS at 24 months was 96.2% and RFS was 89.7%.
Source:
Title:
GILTERITINIB FOR RELAPSED/REFRACTORY FLT3 MUTATED ACUTE MYELOID LEUKEMIAA REAL-WORLD, MULTI-CENTER, MATCHED ANALYSIS
Published date:
05/12/2022
Excerpt:
Twenty-five patients from six academic centers were treated with gilteritinib for FLT3-mutated R/R AML….After a median time of seven months post gilteritinib initiation (range 1-34), 12 patients (48%) achieved complete response (CR) with gilteritinib (figure 1A). The estimated median overall survival (OS) of the entire cohort was eight (CI 95% 0-16.2) months and was significantly higher in patients who achieved CR...
Source:
Title:
Gilteritinib Remains Clinically Active in Relapsed/Refractory FLT3 Mutated AML Previously Treated with FLT3 inhibitors
Published date:
11/04/2020
Excerpt:
...received gilteritinib for treatment of R/R FLT3mut+ AML...co-mutations in DNMT3A, NPM1 and NRAS were observed...Patients with concurrent mutations of PM1/DNMT3A had a trend toward a higher CRc compared to FLT3 mutation alone (71% vs 50%, p= 0.2) but similar survival...
Source:
Title:
RAS MUTATIONS ARE THE DOMINANT MECHANISM OF SECONDARY RESISTANCE TO GILTERITINIB THERAPY FOR RELAPSED/REFRACTORY FLT3-MUTATED AML
Published date:
05/17/2018
Excerpt:
CONTRADICTING EVIDENCE: Adults with R/R FLT3-mutated AML...At study enrollment 26/29 (89.7%) had a FLT3-ITD mutation, including 5 (17.2%) with both FLT3-ITD and FLT3-D835 mutations. Three subjects (10.3%) had a FLT3-D835 mutation only. 23/29 progressed during gilteritinib therapy, 5 were withdrawn for transplant or toxicity, and one remains on gilteritinib in remission.
Trial ID:
Source:
Title:
The impact of FLT3 mutation clearance and treatment response after gilteritinib therapy on overall survival in patients with FLT3 mutation-positive relapsed/refractory acute myeloid leukemia
Excerpt:
A total of 108 patients with FLT3-ITD-positive (FLT3-ITD+) R/R AML were analyzed; 95 of these patients had received ≥80-mg/day gilteritinib...Among patients who received 120-mg/day gilteritinib, those who achieved CR/CRh had a longer median OS (70.6 weeks) and higher 52-week survival probability (66.7%) than patients who did not achieve CR/CRh (n = 71; median OS, 41.7 weeks; 52-week survival probability, 20.2%).
DOI:
10.1002/cam4.3652
Source:
Title:
Selective Inhibition of FLT3 by Gilteritinib in Relapsed/Refractory Acute Myeloid Leukemia: a Multicenter, First-in-human, Open-label, Phase 1/2 Study
Excerpt:
...gilteritinib monotherapy was well tolerated, generated high response rates and durable survival in FLT3mut+ R/R AML patients, including those with both FLT3-ITD and D835 mutations.
DOI:
10.1016/S1470-2045(17)30416-3
Source:
Title:
Gilteritinib in relapsed FLT3-positive Acute Myeloid Leukemia after second allogeneic stem cell transplantation
Published date:
09/03/2020
Excerpt:
Secondly, we present a patient with FLT3-ITD AML...Intrathecal therapy, radiotherapy and gilteritinib to counteract imminent systemic relapse were initiated resulting in a morphological and FLT3-ITD negative CSF.
Source:
Title:
Targeted therapy for medullary and extramedullary relapse of FLT3-ITD acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation
Published date:
08/07/2020
Excerpt:
Treatment with gilteritinib resulted in remarkable response with disappearance of both the medullary and extramedullary tumors....Targeted therapy with gilteritinib for medullary and extramedullary relapse of FLT3-ITD AML could be effective and suitable as a bridging therapy for allo-HSCT.
DOI:
10.1016/j.lrr.2020.100219
Source:
Title:
PHOSPHOPROTEOMIC PROFILING OF PRIMARY AML SAMPLES TO PREDICT EX VIVO RESPONSE TO FLT3-INHIBITORS.
Published date:
05/14/2020
Excerpt:
In liquid culture, FLT3-ITD samples were more responsive to gilteritinib, but not to midostaurin, compared to FLT3-WT samples
Source:
Title:
Gilteritinib, a FLT3/AXL inhibitor, shows antileukemic activity in mouse models of FLT3 mutated acute myeloid leukemia
Excerpt:
Gilteritinib demonstrated potent inhibitory activity against the internal tandem duplication (FLT3-ITD) and FLT3-D835Y point mutations in cellular assays using MV4-11 and MOLM-13 cells…
DOI:
10.1007/s10637-017-0470-z
