U.S. FDA Approves Acalabrutinib (Calquence) with Venetoclax (Venclexta) for Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

On February 20, 2026, the U.S. Food and Drug Administration (FDA) approved acalabrutinib (Calquence, AstraZeneca) with venetoclax (Venclexta, AbbVie/Genentech) as a first-line treatment for adults with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). 

CLL and SLL are slow-growing blood cancers that affect a type of white blood cell called B-lymphocytes. CLL and SLL are the same disease, but the cancerous cells are found in different parts of the body. For CLL, they are mostly found in the blood and bone marrow. In SLL, they are mainly found in the lymph nodes and spleen. Most people are diagnosed with CLL, and those who are diagnosed with SLL will eventually develop CLL. 

CLL is the most common type of leukemia in adults. The American Cancer Society projects that more than 22,000 people will be diagnosed with CLL in the United States in 2026.  

This is the first all-oral, fixed-duration regimen that is approved for CLL. This means that it is given as a pill for a set period of 14 months. In clinical trials, 77% of patients treated with the combination of acalabrutinib and venetoclax had not seen their disease progress after three years. 

“The continuous regimens frequently used to treat chronic lymphocytic leukemia often come with side effects that may become burdensome to patients over time. The US approval of the Calquence combination offers patients an all-oral, 14-month, fixed-duration treatment option that is highly effective and well-tolerated, and gives physicians greater flexibility to tailor treatment plans for individual patient needs and goals,” said Jennifer Brown, MD, PhD, in a press release from AstraZeneca. Dr. Brown is the director of the CLL Center of the Division of Hematologic Malignancies at Dana-Farber Cancer Institute and a professor at Harvard Medical School. 

How does acalabrutinib with venetoclax treat CLL/SLL?

Acalabrutinib is a type of targeted therapy called a Bruton tyrosine kinase (BTK) inhibitor. It blocks a signal from the BTK protein that helps cancer cells grow. It is a pill that is taken every 12 hours. 

Venetoclax is also a type of targeted therapy. It binds to a protein called BCL-2. On cancer cells, there are too many BCL-2 proteins and the cells do not die as they normally would. Venetoclax blocks the BCL-2 proteins and helps cancer cells die as they should. 

Acalabrutinib is given for 14 months. Venetoclax is given for 12 months, starting in the third month. Step-up dosing is needed for venetoclax. 

The study that led to the approval of acalabrutinib with venetoclax

This approval was based on the results from the phase 3 AMPLIFY clinical trial. Of patients treated with acalabrutinib and venetoclax, 77% had no cancer progression at three years. Those patients had a 35% lower risk of disease progression or death compared to those treated with chemoimmunotherapy. 

This combination is already approved in the European Union, Canada, UK, and several other countries. 

What are the common side effects of acalabrutinib with venetoclax?

Acalabrutinib includes warnings for several severe side effects, including:

• Serious and opportunistic infection
• Bleeding problems
• Low blood counts
• Secondary cancers
• Heart problems
• Liver problems

The most common side effects that patients experienced in the trial for acalabrutinib with venetoclax were low blood counts, headache, diarrhea, muscle/bone pain, COVID-19, fatigue, bruising, rash, and nausea. During the clinical trial, around 8% of patients stopped treatment due to side effects. To learn how side effects from CLL therapies are managed, click here. 

Next steps for people living with CLL/SLL

If you or a loved one has been recently diagnosed with CLL/SLL that has not been treated yet, ask your healthcare team if acalabrutinib with venetoclax is right for you. 

Questions to ask your care team about acalabrutinib with venetoclax

Consider asking your care team the following questions about acalabrutinib with venetoclax:

• Is this new approval for acalabrutinib with venetoclax right for me?
• Do I have any conditions that put me at a higher risk of severe side effects with acalabrutinib with venetoclax?
• Are there any other medications I should take with acalabrutinib and venetoclax to prevent severe infections?

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Sources:

• CALQUENCE ® plus venetoclax approved in the US as first all-oral, fixed-duration combination for patients with chronic lymphocytic leukemia in the 1st-line setting
• FDA approves acalabrutinib with venetoclax for chronic lymphocytic leukemia or small lymphocytic lymphoma