From the Guidelines
The 3+7 plus venetoclax regimen is not recommended as the first-line treatment for acute myeloid leukemia (AML) due to the lack of direct evidence supporting its efficacy and safety compared to other established regimens, such as venetoclax combined with hypomethylating agents (HMAs) like azacitidine or decitabine, which have shown improved response rates in AML patients, particularly in older adults or those with adverse genetic features 1. The standard 3+7 induction chemotherapy regimen typically consists of 3 days of an anthracycline (usually daunorubicin at 60-90 mg/m² or idarubicin at 12 mg/m²) plus 7 days of continuous infusion cytarabine (100-200 mg/m²). However, the addition of venetoclax to this regimen is not well-established, and its safety and efficacy are not clearly defined. Some key points to consider when treating AML patients with venetoclax-based regimens include:
- Close monitoring for myelosuppression, tumor lysis syndrome, and infections, with appropriate supportive care including antimicrobial prophylaxis, transfusion support, and possibly growth factor administration during recovery periods 1.
- Consideration of venetoclax dose adjustments when combined with certain antimicrobial agents, such as ciprofloxacin or macrolides, and reduction of venetoclax dose by 75% when combined with posaconazole 1.
- The use of venetoclax in combination with HMAs, such as azacitidine or decitabine, has shown improved response rates in AML patients, particularly in older adults or those with adverse genetic features, and is approved by the FDA for the treatment of newly diagnosed AML in patients aged ≥75 years or those who are otherwise not candidates for intensive remission induction therapy 1.
From the Research
Venetoclax plus 3+7 Regimen
- The combination of venetoclax with the '3+7' regimen, which consists of daunorubicin and cytarabine, has been explored in several studies as a potential treatment for acute myeloid leukemia (AML) 2, 3, 4.
- A phase 1b study found that venetoclax combined with daunorubicin and cytarabine was safe and effective in achieving measurable residual disease (MRD)-negative remissions in newly diagnosed AML patients 2.
- A phase 2 trial demonstrated that the combination of venetoclax with the '3+7' regimen resulted in a high rate of complete remission in adults with AML, with a composite complete remission rate of 91% after one cycle of treatment 3.
- A retrospective analysis compared the efficacy and safety of venetoclax combined with demethylating drugs to the '3+7' regimen and found that the combination of venetoclax and demethylating drugs had a lower degree of myelosuppression, but a similar response rate to intensive chemotherapy 4.
Efficacy and Safety
- The studies suggest that the addition of venetoclax to the '3+7' regimen may improve outcomes for patients with AML, with high complete remission rates and manageable safety profiles 2, 3.
- However, the optimal dosing and duration of venetoclax in combination with the '3+7' regimen require further investigation 2.
- The combination of venetoclax with demethylating drugs may offer an alternative to intensive chemotherapy for some patients, with a lower risk of myelosuppression and infection 4.
Comparison to Standard Treatment
- The '3+7' regimen, consisting of daunorubicin and cytarabine, has been the standard induction regimen for AML for over 40 years 5.
- The addition of venetoclax to this regimen may offer improved outcomes for patients with AML, particularly those with certain genetic mutations that are associated with chemoresistance 2, 3.