Planning Your CLL Treatment Journey: How Doctors Choose Your First Therapy

BTK inhibitors such as acalabrutinib and zanubrutinib are targeted medications that block a protein called Bruton’s tyrosine kinase (BTK), which helps CLL cells survive and grow. The BCL-2 inhibitor venetoclax is often combined with a monoclonal antibody, obinutuzumab.

More recently, a combination of acalabrutinib and venetoclax has also become an option for some patients. All of these treatments are highly effective, but they differ in ways that may make one a better fit than another in your individual case.

Ongoing v. time-limited treatment

One important difference is how long treatment lasts. BTK inhibitors are often taken as a pill every day and continued for as long as they are working and side effects remain manageable.

Because treatment is ongoing, follow-up visits are usually less frequent once the medication has been started and is working well.

In contrast, venetoclax-based treatment is time-limited, meaning treatment is completed after about a year. The newer acalabrutinib-venetoclax combination is also time-limited, with treatment lasting approximately 14 months.

Oral medication v. IV infusions

Another difference is how the medications are given. BTK inhibitors are taken by mouth. Venetoclax is also an oral medication, but when it is used as initial treatment, it is usually combined with obinutuzumab, which is given by intravenous (IV) infusion during the first several months.

Some patients prefer an all-oral treatment, while others do not mind receiving IV infusions if it means treatment has a planned endpoint.

The amount of monitoring also differs. Venetoclax is started gradually because it can cause rapid breakdown of leukemia cells, called tumor lysis syndrome. During the first several weeks, patients need frequent blood tests, extra hydration, and sometimes IV fluids or even a short hospital stay, depending on their individual risk. Once this period is complete, monitoring becomes less intensive.

Continuous BTK inhibitor therapy generally requires less monitoring when treatment begins and fewer clinic visits once patients are doing well.

Additional treatment considerations

Your doctor also considers your overall health and the characteristics of your leukemia.

Certain genetic changes (such as a TP53 mutation or deletion of chromosome 17p) may influence which treatment is recommended because some therapies have shown better long-term results in these high-risk mutations.

“It is very important to take into consideration some basic genetic characteristics of the disease that tells you more about the biology, how the disease behaves,” Dr. Pongas says.

The following health conditions can also impact the choice of treatment:

• Heart disease
• Kidney disease
• Bleeding risk

If one treatment eventually stops working, other treatment options are often used. For example, a patient who starts with a BTK inhibitor may later receive venetoclax-based therapy. Likewise, someone who receives a fixed-duration venetoclax-based treatment or acalabrutinib-venetoclax combination may enjoy years without treatment before another therapy is needed.

Newer medications have expanded options for patients whose leukemia no longer responds to earlier therapies.

When discussing treatment, your doctor may ask questions such as:

• Would you prefer continuous treatment or a treatment with a planned stopping point?
• Do you prefer an all-oral treatment, or are IV infusions acceptable?
• Are you able to come to the clinic more often during the first few months if extra monitoring is needed?
• Do you have other medical conditions that could affect the safety of certain medications?

CLL treatment has improved dramatically over the past decade. Today, most patients can expect highly effective targeted therapies with fewer side effects than traditional chemotherapy.

The best treatment is not the same for everyone. By considering your overall health, the biology of your leukemia, how each treatment is given, the amount of monitoring required, and the options available in the future, you and your healthcare team can choose a treatment plan that best fits your life.

Questions To Ask Your Doctor

• Has my cancer been tested to determine the best targeted therapy path?
• What are the risks v. benefits for each treatment combination?
• How often will I need to be monitored?
• What happens if I can’t tolerate treatment?

Learn more about SurvivorNet's rigorous medical review process.

---