Acute Myelogenous Leukemia - azacitidine - FLT3 mutation

Association details:

Biomarker:	FLT3 mutation
Cancer:	Acute Myelogenous Leukemia
Drug:	azacitidine (DNMT inhibitor)
Direction:	Sensitive

Evidence:

Evidence Level:

Sensitive: B - Late Trials

Source:

Blood

Title:

Prognostic impact of NPM1 and FLT3 mutations in patients with AML in first remission treated with oral azacitidine

Published date:

10/13/2022

Excerpt:

Among patients with NPM1mut, OS and RFS were improved with Oral-AZA by 37% (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.41-0.98) and 45% (HR, 0.55; 95% CI, 0.35-0.84), respectively, vs placebo. Median OS was improved numerically with Oral-AZA among patients with NPM1mut whether without MRD (48.6 months vs 31.4 months with placebo) or with MRD (46.1 months vs 10.0 months with placebo) post-IC. Among patients with FLT3mut, Oral-AZA improved OS and RFS by 37% (HR, 0.63; 95% CI, 0.35-1.12) and 49% (HR, 0.51; 95% CI, 0.27-0.95), respectively, vs placebo.

DOI:

10.1182/blood.2022016293

Trial ID:

QUAZAR AML-001

Evidence Level:

Sensitive: C2 – Inclusion Criteria

New

Source:

clinicaltrialsregister.eu

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....

Trial ID:

2021-005013-14

Evidence Level:

Sensitive: C2 – Inclusion Criteria

New

Source:

clinicaltrials.gov

Title:

Azacitidine and Venetoclax in Treating Patients With High Risk Acute Myeloid Leukemia in Remission

Excerpt:

...FLT3 mutation, history of antecedent hematologic disorder (AHD), presence of dysplasia in the bone marrow, therapy-related AML, history of requiring more than 1 cycle of intensive induction chemotherapy to achieve first remission, or presence of persistent minimal residual disease (detected by cytogenetics, molecular markers, or flow cytometry) at any point after initial induction cycle....

More C2 evidence

Evidence Level:

Sensitive: C2 – Inclusion Criteria

New

Source:

clinicaltrials.gov

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:

NCT01995578

Evidence Level:

Sensitive: C2 – Inclusion Criteria

New

Source:

clinicaltrials.gov

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 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:

NCT01420926

Evidence Level:

Sensitive: C2 – Inclusion Criteria

New

Source:

clinicaltrials.gov

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:

NCT00887068

Evidence Level:

Sensitive: C2 – Inclusion Criteria

New

Source:

clinicaltrials.gov

Title:

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

Excerpt:

......

Trial ID:

UPCI 13-165

Evidence Level:

Sensitive: C3 – Early Trials

Source:

ASH 2021

Title:

Prognostic Impact of NPM1 and FLT3 Mutations at Diagnosis and Presence of Measurable Residual Disease (MRD) after Intensive Chemotherapy (IC) for Patients with Acute Myeloid Leukemia (AML) in Remission: Outcomes from the QUAZAR AML-001 Trial of Oral Azacitidine (Oral-AZA) Maintenance

Published date:

11/04/2021

Excerpt:

In QUAZAR AML-001, pts aged ≥55 years with AML and NCCN intermediate or poor-risk cytogenetics at Dx were randomized 1:1 to receive Oral-AZA 300 mg or PBO QD within 4 mo after attaining first CR/CRi with IC (induction ± consolidation)....In MV analyses, Oral-AZA significantly improved OS vs PBO when adjusted for other variables (P = 0.035); NPM1 status (P = 0.001), FLT3 status (P = 0.035), and cytogenetic risk at Dx (P < 0.001) were each also significantly predictive of OS, as was post-IC MRD status (P < 0.001).

DOI:

10.1182/blood-2021-147465

Trial ID:

QUAZAR AML-001