In November of 2018, Venetoclax was approved in combination with azacitidine, decitabine or low-dose cytarabine for the treatment of newly diagnosed AML in adults who are 75 years or older or who have comorbidities that prevent the use of intensive induction chemotherapy. This FDA approval has greatly expanded available treatment options to many people with AML. 

What is Venetoclax?

Venetoclax is a BCL-2 inhibitor. BCL-2 is a protein that is present in high amounts in AML cancer cells where it helps these cells survive longer in the body and makes them more resistant to chemotherapy. Taking a BCL-2 inhibitor blocks the action of the BCL-2 protein and causes cancer cell death which often slows down the progression of AML.

Common side effects of Venetoclax include low white blood cell count (specifically neutropenia), nausea, anemia, diarrhea, upper respiratory tract infections, fatigue and low platelet count (thrombocytopenia). 

Read about two exciting studies showing the effectiveness of Venetoclax in combination with other drugs:

In June of 2020, a phase III trial called the VIALE-A trial showed a clinically meaningful improvement in response rates and overall survival with venetoclax + azacitidine when compared to azacitidine alone in newly diagnosed elderly patients with AML who were ineligible for intensive chemotherapy. The participants of this study had not been previously treated for their AML. The venetoclax + azacitidine combination prolonged overall survival and increased the likelihood of remission, especially in important mutational subsets like TP53, IDH1 and IDH2.

Results at a median follow-up of 20.5 months:

A phase III trial in 2020 looked at venetoclax in combination with low-dose cytarabine (LDAC). This combination led to greater improvements in remission and overall survival compared to LDAC alone in adults with newly diagnosed AML who were 75 years or older or who had other medical conditions that prevented the use of intensive chemotherapy. Thirty-eight percent of participants in this study had secondary AML, and 20% had received prior hypomethylating agent treatment. The addition of venetoclax to LDAC led to quicker responses compared to LDAC alone. The authors concluded that venetoclax plus LDAC demonstrated a clinically meaningful improvement in remission rate and overall survival vs LDAC alone, with a manageable safety profile. Results from this study confirm venetoclax plus LDAC as an important frontline treatment for AML patients unfit for intensive chemotherapy. 

*not statistically significant **includes Complete remission (CR) plus CR with incomplete blood count recovery

Current Venetoclax Clinical Trials

There are many studies currently being conducted to further test Venetoclax in combination with various other medications. Here are a few that are going on now. Click the link to view more information about each specific trial using our AML Clinical Trial Finder:

• Venetoclax in combination with intensive induction and consolidation chemotherapy in untreated AML
• Venetoclax and azacitidine for non-elderly adult patients with AML
• Liposomal-encapsulated daunorubicin-cytarabine and venetoclax in relapsed, refractory or untreated AML
• Ivosidenib and Venetoclax With or Without Azacitidine in IDH1 Mutated AML
• Magrolimab (a CD47 monoclonal antibody), azacitidine and venetoclax for AML
• Quizartinib (FLT3 inhibitor) and venetoclax in FLT3-mutated AML
• Venetoclax in combination with chemotherapy for relapsed pediatric AML

And many, many others. As you can see, researchers are exploring lots of different possibilities with venetoclax to determine which combinations provide the best results for different subsets of people with AML. There is still much to learn, but it is an extremely exciting time in AML research as we move closer and closer towards a cure for all!