From the Guidelines
The genetic mutations that benefit from the 3+7 plus venetoclax regimen are primarily IDH1/2 mutations, with response rates of 71% and 72%, respectively, in acute myeloid leukemia (AML) patients, as shown in a study published in the Journal of the National Comprehensive Cancer Network 1. This combination therapy involves 3 days of an anthracycline (typically daunorubicin or idarubicin) plus 7 days of cytarabine, combined with venetoclax, a BCL-2 inhibitor. Patients with IDH1/2 mutations show improved response rates with this combination compared to standard chemotherapy alone, as these mutations create metabolic dependencies that venetoclax can exploit. The addition of venetoclax works by blocking the BCL-2 protein that helps leukemia cells survive, making them more susceptible to chemotherapy-induced death. This combination is particularly valuable in these mutation profiles because it targets both the rapid cell division (via traditional chemotherapy) and the apoptotic resistance (via venetoclax) that characterize these genetic subtypes of AML, leading to deeper remissions and potentially improved survival outcomes. Some studies also suggest that patients with NPM1 mutations may benefit from venetoclax-based regimens, although the evidence is not as strong as for IDH1/2 mutations 1. However, patients with TP53 mutations have been shown to have lower response rates to venetoclax-based regimens, with a CR/CRi rate of 47% 1. In contrast, patients with FLT3 mutations have shown variable response rates to venetoclax-based regimens, with some studies suggesting improved outcomes and others showing no significant benefit 1. Therefore, the use of 3+7 plus venetoclax should be considered on a case-by-case basis, taking into account the individual patient's mutation profile and other clinical factors. Key points to consider when using this regimen include:
- IDH1/2 mutations are associated with high response rates to 3+7 plus venetoclax
- NPM1 mutations may also be associated with improved outcomes, although the evidence is not as strong
- TP53 mutations are associated with lower response rates to venetoclax-based regimens
- FLT3 mutations have variable response rates to venetoclax-based regimens, and the use of this regimen should be considered on a case-by-case basis.
From the Research
Genetic Mutations Benefited by 3+7 plus Venetoclax
- The combination of venetoclax with 3+7 daunorubicin and cytarabine chemotherapy has shown efficacy in adults with acute myeloid leukemia (AML) 2.
- Patients with NPM1 mutations have been found to have higher response rates to venetoclax-based regimens 3, 4.
- IDH1/2 mutations have also been associated with favorable outcomes in patients treated with venetoclax-based regimens, particularly when combined with NPM1 mutations 4, 5.
- TET2 and RUNX1 mutations have also been found to be highly responsive to venetoclax-based regimens 4.
- In contrast, patients with FLT3, TP53, and ASXL1 mutations, as well as those with complex karyotypes and secondary AML, have been found to be less responsive to venetoclax-based regimens 4.
Specific Mutations and Response to Venetoclax
- NPM1 mutations: associated with higher response rates to venetoclax-based regimens 3, 4, 5.
- IDH1/2 mutations: associated with favorable outcomes in patients treated with venetoclax-based regimens, particularly when combined with NPM1 mutations 4, 5.
- TET2 mutations: associated with favorable outcomes in patients treated with venetoclax-based regimens 4.
- RUNX1 mutations: associated with favorable outcomes in patients treated with venetoclax-based regimens 4.
- FLT3 mutations: associated with poor response to venetoclax-based regimens 4.
- TP53 mutations: associated with poor response to venetoclax-based regimens 4.
- ASXL1 mutations: associated with poor response to venetoclax-based regimens 4.