BTK Inhibitors: Finding The Right Fit For Chronic Lymphocytic Leukemia (CLL) Patients

“It’s definitely moved away from anything being chemotherapy-centered,” Dr. Soyoung “Sara” Park, a malignant hematologist with Banner MD Anderson Cancer Center in Phoenix, tells SurvivorNet. “These treatments have much more limited toxicity compared to what’s been used in the past.”

Determining When Treatment is Needed

One of the biggest misconceptions about CLL is that treatment starts immediately after diagnosis. In reality, most people are monitored with regular blood work and physical exams until the disease shows signs of progressing. This is called a “watch-and-wait” approach, which allows doctors to monitor the disease until treatment becomes necessary.

“Most of the time… a lot of these patients don’t necessarily need to start on treatment,” Dr. Park says.

Doctors typically recommend treatment if the leukemia begins progressing more rapidly, causes worsening blood counts, enlarging lymph nodes, or starts affecting organs.

When that happens, BTK inhibitors are among the therapies that have transformed CLL care.

BTK Inhibitors Changed the Treatment Landscape

Just a decade ago, chemotherapy was the standard treatment for people whose CLL required therapy.

Dr. Park says BTK inhibitors have been one of the biggest advances in CLL treatment, and there are several available to treat the disease.

Although they all work by blocking the same protein, they differ in their side-effect profiles and approved uses.

BTK inhibitors include:

• Ibrutinib (Imbruvica), the first drug in the class
• Acalabrutinib (Calquence)
• Zanubrutinib (Brukinsa)

Another BTK inhibitor, pirtobrutinib (Jaypirca), is approved for some people whose CLL has returned or progressed after earlier treatment.

While ibrutinib transformed CLL care, newer BTK inhibitors were developed to improve tolerability while preserving effectiveness.

“Now ibrutinib is being utilized even less in CLL because of the more favorable toxicity profile,” Dr. Park says, noting that many patients today receive one of the newer BTK inhibitors instead.

There’s No One-Size-Fits-All Treatment

Although BTK inhibitors are a common first-line option, there isn’t a single “best” choice for everyone. Dr. Park says selecting the right therapy depends on much more than the leukemia itself.

When recommending treatment, doctors consider:

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

“A lot of it is looking at when the patient was diagnosed, the age of the patient, and logistically how often can they come to the clinic,” Dr. Park explains. “Those are the biggest factors… as far as what kind of treatment we choose for that patient.”

For some people, taking a daily pill for as long as it continues to work is the most convenient approach. Others may prefer a fixed-duration treatment that ends after a set period, even if it involves more frequent clinic visits or infusions.

Potential Side Effects and Quality of Life

Dr. Park says experiences vary, and some people require dose adjustments or a switch to a different BTK inhibitor to find the best fit.

“I think some patients either do really well, they just have no issue,” she 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, the most common side effects associated with BTK inhibitors include:

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

If side effects become difficult to manage, doctors can often lower the dose or switch to another BTK inhibitor with a different side-effect profile rather than stopping treatment altogether.

Because many people live with CLL for years — or even decades — finding a treatment they can tolerate is an important part of maintaining their quality of life.

“Generally, BTK inhibitors still feel the least likely to cause a lot of toxicity,” she says.

More Options Mean More Hope

For Dr. Park, one of the most exciting parts of treating CLL today is being able to reassure patients that a diagnosis is no longer the same as it once was.

“We have options for you to continue and increase your longevity,” she says. “It’s not the end just because you have a diagnosis.”

As newer BTK inhibitors and other targeted treatments continue to emerge, doctors have more opportunities to personalize treatment—matching therapy to each person’s disease, lifestyle, and goals while helping many people with CLL live longer and maintain a good quality of life.

Questions To Ask Your Doctor

• Do I need to start treatment now, or is watchful waiting appropriate for me?
• Why might a BTK inhibitor be the best option for me?
• Which BTK inhibitor do you recommend, and why is it the best fit for me?
• Will I need to take this medication indefinitely, or is there a planned end to treatment?
• What side effects should I expect, and how can they be managed?

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