Treatment with BTKis in Chronic Lymphocytic Leukemia - Episode 7
Insights on supportive care and approaches to managing adverse effects of BTK inhibitors in the treatment of chronic lymphocytic leukemia.
Lori A. Leslie, MD: There is a lower incidence of mostly the cardiac adverse effects that you can see with BTK [Bruton tyrosine kinase] inhibitors when you’re looking at the next generation compared with the first generation. What are those adverse effects? I don’t think we’ve touched on that yet. Even though these targeted therapies are well tolerated, there are a few groups of adverse effects that can occur. Some are uncommon but potentially serious, and others are a little more common and typically mild and relatively easy to manage.
Talking just about the less common but potentially serious, the main groups are cardiac adverse effects, you can have an irregular heartbeat called atrial fibrillation or atrial flutter. This is less common with the next-generation BTK inhibitors compared with ibrutinib. If we have patients who have a lot of cardiac comorbidities or have atrial fibrillation at baseline, typically that’s something we use to say we should select next-generation acalabrutinib or zanubrutinib for this patient due to their underlying cardiac comorbidities. That’s reflected more strongly now in the guidelines and has become our standard practice. Even though someone has atrial fibrillation, they certainly are appropriate [patients] to use a BTK inhibitor. We just work with their cardiologist or cardio-oncologist to help know that this might happen and they should be monitored. Another thing that can happen on BTK inhibitors is bleeding. When we’re talking to patients, we like to describe it as like a baby aspirin, so that if they’re having a surgery or a procedure, then they call us. When you’re teaching a patient, what type of advice do you give them about procedures and their BTK inhibitor?
Hoshiyuki Iida, APN: For a patient who’s taking a BTK inhibitor prior to procedures, we usually tell them to hold the therapy 3 days prior to and 3 days after, or a week before and a week after, depending on the procedures.
Lori A. Leslie, MD: It empowers them to talk to their surgeon or provider and say, “I’m on this drug that can cause bleeding. Why don’t you call Hoshi and Lori and see if we should hold it before and after the procedure?” It helps explain it in layman’s terms so they know why it’s important to let us know about that procedure and how they can make sure the procedure is done safely. [As far as] other adverse effects we didn’t talk about yet that are less severe but relatively common, mostly when the patients are first starting their BTK inhibitor, some people can have GI disturbance, gastrointestinal disturbance, like a mildly upset stomach or changes in their bowel movements. We like to empower them and tell them, “This happens, give us a call, but you can take Imodium at home, or you can take this at home.”
Specifically with acalabrutinib, some patients can get a headache when they start, particularly if they’re prone to headaches at baseline. This behaves like a migraine, so caffeine can be helpful. Patients love when we tell them they can drink extra coffee to treat their headache, they are always a fan of that management advice. Again, if a headache happens, it helps them to not be scared and know they can continue their medication, call and let us know. These things are usually a little more transient, so they last the first few weeks to 2 months while on therapy, and then usually get better once the body gets used to the BTK inhibitor.
It’s helpful to let them know that these things might happen and that we’ve got a large panel of patients with CLL [chronic lymphocytic leukemia] that we treat together. In our experience and in the studies, typically these adverse effects are more of an annoyance but can be managed at home with our assistants, and typically are relatively transient, so they shouldn’t expect that this is their new normal. If we can get through those first few months, then patients typically feel much better and can go on with a normal life, just coming to see us every few months to make sure things are going well.
Hoshi, in our patients treated with BTK or otherwise, you run the support groups, you’re an expert here. What type of things do you hear them discussing? What concerns do they have about treatment, adverse effects, or even supportive care that they could pursue?
Hoshiyuki Iida, APN: Most of our patients in our support group have been on a BTK inhibitor for several years, and they are tolerated well. Often our discussions aren’t driven by the adverse effects, or rarely, complications. However, you mentioned a lot of different complications that may occur. We mention that to our patients, and we empower them to call us for any issues, any bleeding that may happen. But we always tell them don’t go reading into the adverse effect profile too much because they’ll list everything on Earth.
Lori A. Leslie, MD: I like normalizing it. I say, if you get worried, read it. We give you the education, if it worries you reading all these things, then read the package insert for Tylenol, acetaminophen, a common over-the-counter drug. It’s 20 pages long and mentions terrifying things. We tell you everything that could happen. Your support group is a wonderful resource to say, “This is what can happen and we watch out for of course, but the most common experience is….” You guys are chatting about other things that go along with being a patient with CLL and not so much that patients are having unacceptable adverse effects on their treatment that impact quality of life.
Hoshiyuki Iida, APN: The main thing that was driven in our support group during COVID-19 was the vaccinations. That is one of the most important things you could do as a preventive measure. For our patients with CLL, they are at a higher risk for COVID-19 and the complications from it. The vaccination and medications such as Paxlovid have been integral to treating patients with COVID-19. The suggestion I would give patients in our support group is, if you tested positive for COVID-19, make sure you alert your health care provider.
Lori A. Leslie, MD: That is something that the COVID-19 pandemic has helped highlight, this particular immunosuppression that patients with CLL have. With their B cells, which are the cancerous cells, the normal role is to make antibodies and protect you. Even in the 2018 CLL guidelines, which was before we even knew COVID-19 was coming, there’s a whole section that highlights the importance of your regular vaccine. An annual flu vaccine, pneumonia vaccine, and shingles vaccine—the Shingrix newer nonlive vaccine—are standard of care for all patients with CLL, even if you’re not at the age where you otherwise would be appropriate for those vaccines. Because of that immune vulnerability, the earlier you start getting those vaccinations in the CLL journey, the more likely that patient is to have longer term immunity that could protect them down the line.
I like to explain it as, please start the vaccines now, and it will help your future self, whether or not you’re on treatment and regardless of what the age is. COVID-19 has been an extension of that. Unfortunately, our patients with CLL, particularly in the beginning of the pandemic were, as you mentioned, at the highest risk of these poor outcomes, admission to the hospital, or having fatal events from COVID-19. It was a terrifying time for our patients.
As we’ve gotten these tools, vaccination, when we have a monoclonal antibody available either for treatment or prevention, things like Paxlovid—antiviral medication you can take—has transformed things for our patients in a way that they can be more comfortable in trying to get a bit more back to normal life. I know you’ve shared in the support group, COVID-19 has been so isolating, and that stress is terrible for our patients’ immune system. Having these tools to empower them has helped us get through the later phase of the pandemic and also helped us highlight this recommendation and importance of vaccines for all patients with CLL, whether or not they’re on treatment. That was present but not well vocalized before we had so much focus on COVID-19.
Transcript edited for clarity.