Clinical Case Scenario: Management Strategies for BTKi Intolerance in Patients With CLL
Experts discuss that for patients with chronic lymphocytic leukemia intolerant to the BTK inhibitor ibrutinib, due to side effects like arthralgia, myalgia, or diarrhea, switching to a second-generation BTK inhibitor can be effective and better tolerated.
Asher A. Chanan-Khan, MD, MBBS: With this particular patient, ibrutinib was stopped and he was taken off the clinical trial based on the cardiology recommendation. Cardioversion was attempted and [was] successful, and the patient was back in sinus rhythm. The patient remained stable for partial remission with a white cell count of 45,000, hemoglobin improved to 12, and platelet counts improved to 105. Now you can see that there’s still disease there, and because ibrutinib was stopped, it’s only a matter of time before it was going to take off. So what should be the next step in the management [of the patient’s disease]? No further treatment should be given to this patient? Or [do we] reinitiate ibrutinib, even though the patient is no longer [responsive]…. I think we addressed that. I think Dr [Pooja] Advani, you mentioned that if you are going to start it, it should be continued because the patient is responding to…the second. This is the answer I think I would take. BTK [Bruton tyrosine kinase] is now contraindication. We addressed that issue as well. But what we did not address was, I think, intolerance. If this patient was or is deemed intolerant to CLL [chronic lymphocytic leukemia][treatment], there may be other reasons. I’ve had patients who had hip and joint pain to the point they actually ended up needing more surgical intervention. So what data do you have, Dr [Ricardo] Parrondo, that would suggest when patients are intolerant to a BTK: [Do] they take it for whatever reason, or they were taken off? We talked a lot about AFib [atrial fibrillation].There are other reasons, such as diarrhea, musculoskeletal reasons, or bleeding disorders. If they’re intolerant, what approach would you take in such a patient?
Ricardo Parrondo, MD In terms of BTK intolerance, I would define that concept as intolerable adverse effects, despite maximum supportive care, despite holding and restarting a BTK inhibitor [BTKi]. In the case of ibrutinib, [that would be] persistent adverse effects despite dose reductions of ibrutinib, from 280 to 140. And we know we have data [showing] that treatment discontinuation due to BTK intolerance occurs less frequently with acalabrutinib and zanubrutinib, somewhere in the range of 10% to 15% compared with ibrutinib, which is as low as 20%, and [according to] some reports, as high as 50% over time. So patients who are intolerant to ibrutinib, it’s OK to switch them to another covalent BTKi because they’re not resistant to it. And it’s all based on the adverse event profile of the drugs. So, for example, if patients have intolerable arthralgia and myalgia on ibrutinib, changing the patient to a second-generation BTKi is the correct thing to do because they have less arthralgia and myalgia. Or, for example, if a patient is on acalabrutinib and develops difficult-to-control headaches, which are a known adverse effect of acalabrutinib, then switching them to zanubrutinib would be the correct choice in my mind. To me, the most common causes of BTK intolerance are fatigue, arthralgia, and myalgia, you know, these musculoskeletal complaints, diarrhea, and bleeding and bruising events. So those can be quite difficult and can be quite distressing to the patients. But as I was saying earlier, the second-generation BTKis are better tolerated than ibrutinib. So if a patient is on ibrutinib, switching them to a second-generation BTKi and not giving up on the BTK pathway. Try changing them to another BTKi because they may tolerate it better.
