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Association details:
Biomarker:FLT3 mutation
Cancer:Acute Myelogenous Leukemia
Drug:azacitidine (DNA methylation inhibitor)
Regimen:HDA (cytarabine + daunorubicin + Synribo (omacetaxine mepesuccinate))
Direction:Sensitive
Evidence:
Evidence Level:
Sensitive: C2 – Inclusion Criteria
Title:

Study of experimental drug NMS-03592088 in combination with azacitidine in adult patients with blood malignancies Studio del farmaco sperimentale NMS-03592088 in combinazione con azacitidina in pazienti adulti con tumori maligni del sangue

Excerpt:
...Fase I:• Tossicità limitanti della dose (dose limiting toxicity, DLT) al primo ciclo;Fase II:• LMA con FLT3-mutato: Tasso di Remissione Completa Composita (CRc: CR +CRi), cioè Remissione Completa (CR)+ Remissione Completa con recupero ematologico incompleto (CRi), come determinato dagli Sperimentatori sulla base delle raccomandazioni European LeukemiaNet (ELN) del 2017.• LMMC: Tasso di Risposta Globale, cioè Risposta Completa (CR) + Remissione citogenetica completa (CCR) + Remissione Parziale (PR) + Risposta Midollare (MR) + Beneficio Clinico (CB) come definito dai criteri dell'International Working Group (IWG) specifici della malattia....
Evidence Level:
Sensitive: C2 – Inclusion Criteria
Title:

Maintenance Low Dose 5'-Azacitidine Post T Cell Depleted Allogeneic Stem Cell Transplantation for Patients With Myelodysplastic Syndrome and Acute Myelogenous Leukemia With High Risk for Post-Transplant Relapse

Excerpt:
...- Acute myelogenous leukemia (AML) in first remission that required more than 1 cycle of treatment to achieve remission or with the following cytogenetic abnormalities: FLT3 mutation, deletion/monosomy of chromosome 5 or 7, MLL gene rearrangement, or more than or equal to 3 cytogenetics abnormalities....
Trial ID:
More C2 evidence
Evidence Level:
Sensitive: C2 – Inclusion Criteria
Title:

Decitabine With or Without Bortezomib in Treating Older Patients With Acute Myeloid Leukemia

Excerpt:
...- Acute myeloid leukemia with t(8;21)(q22;q22); RUNX1-RUNXT1 as determined by the Ohio State University (OSU) Molecular Reference Laboratory, per Cancer and Leukemia Group B (CALGB) 20202; however patients who (1) are >= 75 years; and/or (2) have an ejection fraction of < 40%; and/or (3) have a performance status of > 2, may be registered to CALGB 20202 and registered and treated on CALGB 11002 prior to receiving the FLT3 mutation and core-binding factor (CBF) molecular screening results from CALGB 20202...
Trial ID:
Evidence Level:
Sensitive: C2 – Inclusion Criteria
Title:

Controlled Study of Post-transplant Azacitidine for Prevention of Acute Myelogenous Leukemia and Myelodysplastic Syndrome Relapse (VZ-AML-PI-0129)

Excerpt:
...- Induction Failure, relapsed disease or second or greater remission; patients in first complete remission that required more than 1 cycle of treatment to achieve the remission, or that have AML evolving from MDS, or that had the following abnormalities: FLT3 mutation, deletion of chromosome 5 or 7, MLL gene rearrangement, or more than or equal to 3 cytogenetics abnormalities....
Trial ID:
Evidence Level:
Sensitive: C2 – Inclusion Criteria
Title:

Phase II Study of 5-azacytidine Maintenance After Transplant for AML or MDS

Excerpt:
...- Fms-like tyrosine kinase 3 (FLT3) mutation...
Trial ID:
Less C2 evidence
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

1420 Azacitidine Combined with Homoharringtonine, Idarubicin/Daunorubicin, Cytarabine for Previously Untreated Patients with Acute Myeloid Leukemia: A Single-Center, Phase 2 Study

Published date:
11/03/2022
Excerpt:
The CR/CRi was achieved in 95.0% (19/20) (Fig. 1B). 94.7% (18/19) reached CR/CRi after the 1st cycle of induction therapy and the median time was 25.0d (IQR, 21.0 to 27.0)...The estimated 2-year OS and RFS were 87.4% (95%CI, 58.1% to 96.7%) (Fig. 1C) and 82.0% (95%CI, 53.1% to 94.0%), respectively (Fig. 1D). No survival difference was observed between the favorable and intermediate versus poor-risk groups in both OS and RFS (Fig. 1E& 1F). Meanwhile, the estimated 2-year OS and RFS possibility of the favorable and intermediate-risk group was 90.9% (95%CI, 50.8% to 98.7%) and 80.0% (95%CI, 20.4% to 96.9%), respectively (Fig. 1E& 1F).We detected 30 mutants in 17 of 58 leukemia driver genes at the timepoint of enrollment. The median mutation number/patient was 1.50 (range, 0-4), and 17 of 20 (85.0%) patients had more than one mutation (≥1) (Fig. 1G). The most frequently mutated genes were FLT3 (ITD/TKD) (20.0%), KIT (15.0%), NRAS (15.0%), and DNMT3A (15.0%) (Fig. 1G). More than half of the patients (11/20) harbored the mutated genes involved in signal transducers (FLT3, KRAS, NRAS, KIT, PTPN11, CSF3R; 11/20, 55.0%), and all these patients achieved CR/CRi (11/11, 100%) after induction therapy (Fig 1G).This trial demonstrated that the adding of Aza to HIA/HDA regimen is an effective first-line therapy for previously untreated young or fit AML patients, with high efficacy and well tolerance.
DOI:
https://doi.org/10.1182/blood-2022-164898
Trial ID: