Understanding BTK Inhibitors Role in Treating CLL
- A class of drugs called Bruton’s tyrosine kinase (BTK) inhibitors have led to a lot of hope when it comes to treating chronic lymphocytic leukemia (CLL).
- BTK inhibitors are a type of targeted therapy. They work by blocking signals to the B-cell receptor (BCR).
- Right now, two BTK inhibitors, ibrutinib and acalabrutinib, are approved for the treatment of CLL.
- Studies are currently underway to determine which of the targeted therapies are the best options and in which order these drugs should be given.
Many different drugs or drug combinations can be given as a first treatment for CLL, and several factors must be taken into consideration to determine which is the best approach. This includes:
- A patient’s age
- Overall health
- Prognostic factors
What Are BTK Inhibitors And When Are They Used?
BTK inhibitors are a type of targeted therapy, meaning they will target cancer specifically rather than attacking the rest of the body and hoping to kill the cancer in the process (which is what chemo does). “BTK inhibitors are really elegantly designed,” Dr. James Gerson, a hematologist at Penn Medicine, told SurvivorNet. “The way I like to think about it is that there’s a light switch that’s turned on in the cancer. And if we can just turn off that light switch, then the cancer will stop growing. It won’t necessarily die completely or go away, but it’ll at least stop growing.”Dr. James Gerson explains how BTK inhibitors work
Another type of BTK inhibitor, acalabrutinib, was approved more recently and was developed to have fewer side effects than ibrutinib. Common drug combinations to treat CLL are:
- Ibrutinib (Imbruvica) with a monoclonal antibody called rituximab (Rituxan)
- Acalabrutinib (Calquence) with a monoclonal antibody called obitnutuzumab (Gazyva)
There are other approaches, and both of the inhibitors can also be administered on their own as well. Zanubrutinib (Brukinsa) is the newest BTK inhibitor, and may be an option when others aren’t.
In a previous conversation with SurvivorNet, Dr. Nicole Lamanna, a leukemia specialist at Columbia University Medical Center, said that the recent drug approvals have “transformed” the way CLL is treated.
"BTK inhibitors have definitely moved the bar in CLL and improved CLL survival, but you take these pills indefinitely, like a chronic medical illness," Dr. Lamanna explained. “In other words, just like a blood pressure medicine or a diabetic medicine, you take them every day as long as you’re tolerating them, as long as you’re not having any particular side effects, and as long as they’re working.”
Dr. Nicole Lamanna explains how new approvals have changed the game for treating CLL.
“Now, the problem that we’re encountering is just like our other internal medicine colleagues or other physicians: many patients don’t want to be on a pill for the rest of their life … And so what we’re trying to do is, can we start combining some of these oral agents with even some gentler IV treatments, seeing if we can get people into a deeper remission.”
Are BTK Inhibitors Effective?
There is increasing evidence showing that BTK inhibitors can have positive results, and be both more effective and better tolerated than former standards of care.
“Traditionally, we treated patients with CLL with drugs like chemotherapy in combination with antibodies, such as rituximab, but in the last few years, we’ve seen a variety of new targeted therapies that are efficacious in this disease and it’s really changing the way we treat patients with CLL,” Dr. Jennifer Crombie, who works in Dana-Farber Cancer Institute’s Lymphoma Program, told SurvivorNet.
“Studies have now been focused on looking at comparing targeted agents to chemotherapy, and for many patients, these targeted agents seem to be better tolerated, and in some cases, more efficacious,” Dr. Crombie continued. “Just recently, there’s been a few new approvals, including the drug, acalabrutinib … [this drug] is a next generation BTK inhibitor, which is slightly more specific for the BTK target, as compared to ibrutinib, and it is thought to potentially be less toxic with decreased side effects.”
Some of the common side effects associated with BTK inhibitors include:
- Lower than normal levels of white and red blood cells
- Diarrhea
- Nausea
- Fatigue
- Body aches
- Muscle and joint pain
It’s important to speak to your doctor early on about the potential benefits of taking BTK inhibitors, what side effects to be aware of, and what to do if you begin experiencing side effects.
The Future of CLL Treatment
Dr. Crombie stressed that the approvals of new drugs and treatment tactics for CLL come with a lot of questions as well. Namely, what is the best approach to treating this disease?
“One question is, which of the targeted therapies are better to use and in which order?” Dr. Crombie noted. “The other big question is, can we combine these agents to make responses deeper for patients and potentially allow patients to discontinue therapy if they have a really deep response? We can measure this by looking at something called minimal residual disease (MRD).
“So, we’re incorporating this now into trials to see if patients who have really good responses can take a break from their therapy and continue to be monitored closely for recurrence and potentially restart them if needed,” she continued. “So, these are all questions that are being looked at now in clinical trials, and hopefully we’ll get the answers too in the upcoming years.”
Questions to Ask Your Doctor
- Is a BTK inhibitor or a drug combination right for me?
- What are the possible side effects from this treatment?
- Are there clinical trials I can/should consider taking part in?
- What are the risks vs. benefits of this type of treatment?
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