From the Guidelines

Venetoclax works by inhibiting the B-cell lymphoma-2 (BCL-2) protein, resulting in programmed cell death of leukemia cells.

Venetoclax is a BH3 mimetic that blocks the anti-apoptotic BCL-2 protein, leading to apoptosis of leukemia cells 1.
The overexpression of BCL-2 contributes to lymphoid and myeloid malignancies, making it a target for therapy.
By inhibiting BCL-2, venetoclax induces cell death in leukemia cells, resulting in a clinical response.

Venetoclax is approved in combination with hypomethylating agents such as azacitidine or decitabine for patients with newly diagnosed AML who are ineligible for intensive chemotherapy 1.
The recommended dose of venetoclax is 400 mg, with a gradual stepwise ramp-up over 5 weeks to mitigate the risk of tumor lysis syndrome (TLS) 1.
Venetoclax has shown promising activity in patients with relapsed or refractory CLL, with an overall response rate (ORR) of 79.4% and a median progression-free survival (PFS) of 72% 1.
Common adverse events associated with venetoclax include neutropenia, thrombocytopenia, anemia, and decreased lymphocyte count 1.
Venetoclax has also been evaluated in combination with low-dose cytarabine, with a CR/CRi rate of 54% and a median duration of remission of 8.1 months in older patients with previously untreated AML ineligible for intensive chemotherapy 1.

From the Research

Venetoclax is a highly selective and effective B-cell lymphoma-2 (BCL-2) inhibitor, which is able to reinstate the apoptotic potential of cancer cells 2, 3.
The drug works by inhibiting the antiapoptotic protein BCL-2, allowing the deregulated process of apoptosis in malignant cells to restart 3.
Venetoclax has a novel mechanism of action, with a convenient oral once-daily regimen, making it an important option for treating relapsed or refractory chronic lymphocytic leukemia (CLL) 4.

Venetoclax has shown remarkable efficacy in CLL, both as monotherapy and in combination therapy, with fixed-duration combination therapy of venetoclax with anti-CD20 antibody now being the standard of care in numerous countries 2.
The drug has also demonstrated encouraging outcomes in acute myeloid leukemia (AML) and multiple myeloma, particularly in patients with translocation t(11;14) 2, 3.
Venetoclax-based therapy is an excellent treatment option for patients interested in time-limited therapy and can be offered in both the front-line and relapsed/refractory settings 5.

Despite its efficacy, venetoclax treatment is not curative, and clonal evolution and disease relapse appear to be the norm over time 2.
Various distinct resistance mechanisms have been identified, frequently emerging in a sub-clonal pattern, and further research is needed to understand the complex interplay of factors involved in resistance to venetoclax 2, 6.