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Association details:
| Biomarker: | NRAS mutation |
|---|---|
| Cancer: | Acute Myelogenous Leukemia |
| Drug: | Venclexta (venetoclax) (Bcl2 inhibitor) |
| Direction: | Resistant |
Evidence:
Source:
Title:
Venetoclax to Improve Outcomes of Fractionated Busulfan Regimen in Patients With High-Risk AML and MDS
Excerpt:
...Mutated P53 or Ras pathway genes (CBL, NRAS, KRAS, NF1, PTPN1) or DNMT 3a or ASXL1 or RUNX1 3....
Trial ID:
Source:
Title:
Venetoclax Added to Fludarabine + Busulfan Prior to Transplant and to Maintenance Therapy for AML, MDS, and MDS/MPN
Excerpt:
...- Prescence of mutation in the RAS pathway including NRAS, KRAS, PTPN11, CBL, NF1, RIT1, FLT3, and KIT...
Trial ID:
Less C2 evidence
Source:
Title:
837 Association of Genetic Characteristics with Response to Venetoclax Plus Hypomethylating Agents in Relapsed and Refractory Acute Myeloid Leukemia
Published date:
11/03/2022
Excerpt:
In this study, we aimed to evaluate the efficacy of VEN combined with hypomethylating agents (HMA) and identify the potentially predictive factors for response in R/R AML....Mutations in IDH1/2, NPM1 and ASXL1 predicted superior response to VEN-based therapy (CRc: 78.3%, 70.8% and 65.0%, respectively), while mutations in active signaling, such as FLT3-ITD, K/NRAS predicted inferior response (CRc: 29.0% and 28.6%).
Secondary therapy:
Hypomethylating agent
DOI:
https://doi.org/10.1182/blood-2022-158762
Source:
Title:
537 Outcome of Patients with Acute Myeloid Leukemia Following Failure of Front-Line Venetoclax Plus Hypomethylating Agent Therapy
Published date:
11/03/2022
Excerpt:
Patients with AML who received front-line Ven+HMA outside clinical trials at the Mayo Clinic between 2018 and 2020 were retrospectively recruited...The current study identifies presence of TP53 and K/NRAS mutations as predictors of inferior survival in patients with AML relapsed or refractory to front-line Ven+HMA.
Secondary therapy:
Hypomethylating agent
DOI:
https://doi.org/10.1182/blood-2022-165491
Source:
Title:
Genetic characteristics predict response to venetoclax plus hypomethylating agents in relapsed or refractory acute myeloid leukemia
Published date:
10/25/2022
Excerpt:
With a median follow-up of 11.2 (95%CI, 7.2-14.8) months, 1- and 2-year overall survival were 46.9% (95% CI, 37.8%-58.1%) and 38.9% (95% CI, 28.7%-52.9%), respectively…Mutations in IDH1/2, NPM1, ASXL1 and chromatin-cohesin genes predicted superior response to VEN-based therapy, whereas mutations in active signaling genes such as FLT3-ITD and K/NRAS predicted inferior response...VEN combined with HMA was effective with R/R AML patients, and the response to treatment was associated with genetic characteristics.
Secondary therapy:
Hypomethylating agent
DOI:
10.1111/joim.13581
Source:
Title:
Clinical and molecular predictors of response and survival following venetoclax therapy in relapsed/refractory AML
Published date:
03/09/2021
Excerpt:
...86 patients with RR-AML who were treated with venetoclax combinations...Azacitidine + venetoclax resulted in higher response rates compared with low-dose cytarabine + venetoclax...Mutations in NPM1 were associated with higher response rates, whereas adverse cytogenetics and mutations in TP53, KRAS/NRAS, and SF3B1 were associated with worse OS.
Secondary therapy:
azacitidine
DOI:
10.1182/bloodadvances.2020003734
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:
DEC10-VEN is an effective regimen for AML. Addition of FLT3i to DEC10-VEN was safe and may improve upon responses in FLT3mut pts. Mutations in NPM1 and DNA methylation pathways were associated with more durable responses while mutations in ASXL1, RAS and TP53 were associated with refractory disease or relapse.
DOI:
10.1182/blood-2019-128547
Trial ID:
