SOHO 2026 | Pirtobrutinib and venetoclax in relapsed CLL: factors guiding treatment selection and sequencing

So the patients who are failing on a covalent BTK inhibitor, such as ibrutinib, acalabrutinib, and zanubrutinib, and depending on if they have received previously a BCL2 inhibitor, such as venetoclax, if they have already received that, then really one of the more practical options is a non-covalent BTK inhibitor, such as pirtobrutinib. There are also other therapies such as CAR T-cell therapy, which is approved. But I think pirtobrutinib is widely used in that setting once a patient has failed a covalent BTK inhibitor because of the ease of initiation and it’s just, you know, kind of a pill every day. I think pirtobrutinib is a very safe BTK inhibitor. Yes, you can have still the BTK side effect like atrial fibrillation and some hypertension or bleeding complications. But numerically, the rates are much lower than ibrutinib for sure. And I think they are comparable, if not, maybe better. But I think in the similar ballpark, I would say with acalabrutinib and zanubrutinib. So certainly if a patient was on a BTK inhibitor, covalent BTK inhibitor, they’re failing that BTK inhibitor, I think pirtobrutinib would be a very appropriate choice to use. As I said, if a patient has not had a venetoclax-based therapy yet, and I think so that could also be considered for an individual patient, you know, and I think those are one of the things where a patient wants to be on a continuous therapy for a long time again with pirtobrutinib. Or maybe they want to try with pirtobrutinib. I’m sorry, venetoclax plus rituximab for a timely two-year approach. You know, I think so those are discussions with the patient. And a decision could be made based on cardiovascular history, maybe the need for anticoagulation. If they have an elevated creatinine, then maybe venetoclax-based therapy may not be most important or more appropriate to say. If they have significant bulky lymph nodes, more risk of TLS with venetoclax-based therapy, so more so maybe consider pirtobrutinib. So those are kind of, I guess, finer points which clinicians can consider deciding between pirtobrutinib and ven-based therapy in the lab CLL. And many times maybe it comes down to the patient preference and decision what they want to do.

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