A Specialist’s Answers for Common CLL Questions: Treatment Timing, Therapy Options, Handling Watch-and-Wait, and More

Discover what CLL specialist Dr. Meghan Thompson shared during a question-and-answer webinar for people with chronic lymphocytic leukemia (CLL). Learn about the topics covered, like when to see a specialist, how doctors decide when treatment is needed, what today’s treatment options look like, and more. Click here to watch the full webinar recording. 

Why seeing a CLL specialist can help your care plan

CLL is the most common type of leukemia in the United States. Because CLL care has changed quickly over the past decade, it is recommended that patients see a medical oncologist with experience in blood cancers or a hematologist. A hematologist is a doctor who treats blood conditions. To view the CLL specialist directory, click here. 

Dr. Thompson stressed that not everyone with CLL needs treatment right away. 

“Approximately a third of patients need treatment right at the time of diagnosis, another third will never need treatment, and another third don’t need treatment right at diagnosis but will need treatment at some point during their lifetime.” 

For many patients, a strategy called watch-and-wait may be the best option. This is when doctors monitor you to see if your cancer gets worse before giving medication to treat the cancer. Some people may find it challenging to know they have cancer and not receive active treatment. But watch-and-wait is done when doctors know that: 

• Earlier treatment does not necessarily improve patient outcomes.
• The risks of treatment outweigh the benefits at that stage.  

Even during watch-and-wait, CLL can weaken the immune system and raise the risk of infections and secondary cancers. A specialist can help you understand if watch-and-wait is safe for you, when it might be time to start therapy, and how to reduce your risk of getting infections. 

When does CLL treatment become necessary?

To monitor patients with CLL, doctors look at several factors over time, not one lab number. Regular visits often include a complete blood count (CBC), which measures:

• White blood cells. In CLL, the affected cells are abnormal B lymphocytes, a type of white blood cell that builds up.
• Hemoglobin. This reflects red blood cells that carry oxygen.
• Platelets. Platelets are a type of blood cell that help blood clot. 

There is no single cutoff, but doctors pay close attention when hemoglobin is around 10 or lower, or platelets drop under 100,000, especially if those numbers are worsening. Doctors also check lymph nodes by exam and assess the spleen. The spleen is an organ on the left side of the abdomen that can enlarge in CLL. Symptoms also matter, including ongoing drenching night sweats, fevers, and fatigue that does not improve.

If you understand the signs your care team watches for, you can track symptoms, ask clearer questions at visits, and feel more prepared when treatment decisions come up. 

Tests that help match treatment to your CLL

Before choosing a first treatment, it's important to test the biology of your CLL, meaning the features of the CLL cells that can affect how treatment works. 

Two common areas include:

• IGHV mutation status: A fixed characteristic that does not change over time and usually needs testing only once.
• p53 status: A key safety gene that helps damaged cells die. In CLL, problems in p53 can raise risk. This can include deletion 17p found by a test called fluorescence in situ hybridization (FISH), or a p53 mutation found by next-generation sequencing, a detailed DNA test. 

These results can help you and your CLL specialist compare options more accurately, including how long remission may last with different approaches. 

Current first treatment options and how they differ

Chemotherapy is rarely recommended as a first CLL treatment now, because newer targeted medicines work well and have fewer long-term side effects. 

She outlined three main approaches:

1. Venetoclax plus obinutuzumab: Venetoclax (Venclexta, AbbVie/Genentech) is a targeted pill combined with an antibody infusion called obinutuzumab (Gazyva, Genentech). This is often a fixed-duration plan for about one year, with infusions in the first six months.
2. BTK inhibitors: These block a growth signal in CLL cells. Examples include acalabrutinib (Calquence, AstraZeneca) and zanubrutinib (Brukinsa, BeOne). They are usually taken continuously until CLL worsens or side effects outweigh the benefits of treatment.
3. Combination targeted pills: Some clinical trials and guidelines include combinations such as a BTK inhibitor plus venetoclax, sometimes with an antibody, often aiming for deep remission and time-limited therapy. 

A recent head-to-head study presented at the American Society of Hematology (ASH) meeting showed similar progression-free survival between a BTK inhibitor and venetoclax-based treatment. Read our article about this topic here: Comparing Fixed-Duration vs Continuous Treatment for CLL. 

If more than one option is reasonable, your values matter, like whether you prefer a time-limited plan or a longer-term daily pill. To continue reading about things to consider when selecting a CLL treatment, click here. 

Making treatment choices: logistics, side effects, and other health conditions

A theme in Dr. Thompson’s answers was personalization. She encouraged patients to ask their doctor to walk through all standard options and any clinical trials. Logistics can also differ. Venetoclax-based plans often require more time early on spent at the clinic because the dose is slowly increased to lower the risk of tumor lysis syndrome, a rare but serious reaction caused by the rapid breakdown of cancer cells.

Other health conditions you have may influence which treatment is chosen. For example, BTK inhibitors like ibrutinib can raise the risk of an irregular heartbeat called atrial fibrillation, bleeding, and high blood pressure. Venetoclax can be harder to start for people with kidney problems. Bring a full list of your medicines and health conditions to visits. It can directly affect which therapy fits you best. 

“Make sure your doctor is aware of all of your other medical issues and other medications because there are specific side effects that might steer the treatment selection.”

What’s new: BTK degraders and other research

BTK degraders are a newer approach being tested in clinical trials. Instead of blocking BTK, they help break down the BTK protein, which may work even when resistance mutations develop. Several BTK degraders are in clinical trials, and at least one called BGB-16673 has moved into a phase 3 study. 

She also highlighted minimal residual disease (MRD) testing. MRD is a sensitive blood test that looks for tiny amounts of CLL left after treatment. Some trials are using MRD to guide how long a patient stays on therapy.

If CLL has returned after prior therapies, or if you want time-limited strategies, ask your CLL specialist whether a clinical trial using BTK degraders or MRD-guided treatment is available near you. 

Living well during watch-and-wait

Patients asked what they can do during watch-and-wait. Dr. Thompson recommended focusing on: 

• Infection prevention and routine health screening
• Staying up to date on non-live versions of vaccines
• Regular skin checks with a dermatologist because skin cancers are more common in people with CLL
• Keeping up with other routine screening, like colonoscopies and mammograms 

Continue reading about this topic: Understanding Secondary Cancer Risks in CLL: Signs, Screening, and Prevention. 

On foods and supplements, more research is needed in CLL. She suggested correcting true deficiencies like vitamin D or B12 if labs show they are low. For other supplements, discuss them with your doctor due to limited regulation, possible side effects, and interactions.

Read some of the research in the following articles: 

• CLL Specialist Shares Proven Exercise and Nutrition Tips to Help Patients Reduce Fatigue
• Effects of Vitamin D Supplementation for CLL Patients in Watch-and-Wait

Watch-and-wait is still active care. Preventing infections and catching other cancers early can protect your health while you monitor CLL. 

Key takeaways for people with CLL 

Dr. Thompson’s answers showed that CLL care is often a long-term plan with many options. The best next step is usually a specialist-guided plan that includes the right genetic testing, routine monitoring, and infection prevention. When treatment is needed, choices often depend on your CLL features, other health conditions, and personal preferences. 

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