The ‘Watch and Wait’ Approach To CLL Treatment: How Doctors Determine When To Begin Therapy

What is the ‘Watch & Wait’ Approach?

• Regular blood work
• Physical exams
• Symptom tracking

This approach, known as watchful waiting or active surveillance, allows patients to avoid treatment until it’s actually needed.

Research has shown that starting therapy before CLL begins causing problems does not improve outcomes for most patients. Instead, doctors carefully watch for evidence that the disease is becoming more active.

What Symptoms Should You Watch For?

One of the most common questions Dr. Park hears from patients is what they should be looking for while they’re practicing watchful waiting.

“I always advise them, check your neck, check underneath your arms for any enlarged lymph nodes because you want to get an idea of what normal feels like,” she says.

Dr. Park recommends checking once or twice each week so you’ll recognize if something changes. Because lymph nodes commonly swell after infections or inflammation, she says not every swollen lymph node is cause for concern. However, if swelling lasts for two weeks or longer instead of resolving, patients should contact their hematologist.

In addition to persistent swollen lymph nodes, Dr. Park recommends reporting:

• Drenching night sweats (lasting at least two weeks)
• Unexplained fatigue
• Any other new or worsening symptoms

“I think these are definitely symptoms when they show up, you want to alert your hematologist because then we want to investigate,” she says.

How Doctors Know It’s Time to Start Treatment

Symptoms are only part of the picture. Doctors also follow blood tests and imaging over time to determine whether CLL is progressing.

According to Dr. Park, treatment may be recommended when:

• White blood cell counts begin rising rapidly over time
• Blood tests show CLL is causing anemia or other abnormal blood counts
• Lymph nodes become significantly larger or begin causing discomfort
• Enlarged lymph nodes threaten nearby organs or other structures

“When we see any signs of blood work that concern us that it’s associated with the CLL, then that is also an indication to start treatment,” Dr. Park explains.

The goal is to treat the disease once it starts impacting quality of life and health, not necessarily right after a diagnosis.

Modern CLL Treatment Options

When treatment does become necessary, today’s options look very different than they did just a decade ago.

“It’s definitely moved away from anything being chemotherapy-centered,” Dr. Park says.

For years, chemotherapy was the primary treatment for CLL. Today, many patients receive targeted therapies that attack specific proteins leukemia cells need to survive while generally causing fewer side effects than traditional chemotherapy.

Among the most commonly prescribed first-line treatments are Bruton tyrosine kinase (BTK) inhibitors, oral medications that block a protein helping CLL cells grow and survive.

“When ibrutinib, which is one of the first BTK inhibitors, came out, it was basically a huge game changer because this was something with low toxicity and just not the same toxicity as traditional chemotherapy,” Dr. Park says.

Several BTK inhibitors are now available, including:

• Ibrutinib (Imbruvica)
• Acalabrutinib (Calquence)
• Zanubrutinib (Brukinsa)

A newer BTK inhibitor, pirtobrutinib (Jaypirca), is currently approved for certain patients whose disease has returned after previous treatment.

Although these medications work by targeting the same protein, they differ in their side-effect profiles.

Ibrutinib is being utilized less in CLL these days as BTK inhibitors with favorable side effect profiles become available, Dr. Park says.

Choosing The Right Treatment Is Personal

Although BTK inhibitors are a common first-line option, there isn’t a single “best” treatment for everyone.

Instead, Dr. Park says physicians work with patients to choose an approach that fits both their medical needs and their lifestyle.

Some targeted therapies are taken as daily pills indefinitely, for as long as they continue working. Other treatment approaches combine oral medications with infusions for a fixed period of time.

“I think a lot of it is when they were diagnosed … the age of the patient and logistically how often can they come to the clinic,” Dr. Park says. “Those are … the biggest factors as far as what kind of treatment we choose for that patient.”

When recommending treatment, doctors may consider:

• Whether a patient prefers continuous treatment or a fixed-duration regimen
• Age and overall health
• Potential side effects
• How frequently they can travel to appointments
• Personal preferences and lifestyle

For some patients, the convenience of taking a pill every day is the best fit. Others prefer a treatment plan with a defined end date, even if it requires more clinic visits.

What To Expect From BTK Inhibitors

Like any medication, BTK inhibitors can cause side effects. However, many people tolerate them well.

“I think some patients either do really well, they just have no issue,” Dr. Park says. “Or sometimes it’s just a little bit of trial and error figuring out that dose that really works for them.”

According to Dr. Park, common side effects include:

• Fatigue
• Headaches
• Bruising or bleeding, particularly with older BTK inhibitors such as ibrutinib

Fortunately, side effects don’t always mean treatment has to stop. If symptoms become difficult to manage, doctors can often lower the dose or switch to another BTK inhibitor with a different side-effect profile.

“Generally, I think from a standpoint when starting therapy, BTK inhibitors still feel… the least likely to cause a lot of toxicity,” Dr. Park says.

Because many people live with CLL for years, finding a treatment patients can comfortably stay on is an important part of long-term disease management.

Questions To Ask Your Doctor

• What symptoms should I be monitoring for?
• How often do I need to come in for testing while monitoring CLL?
• What first, or first-line, treatment do you recommend in my case?
• What are my options if side effects become too difficult?

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