Comparative Data, Safety Profiles, and Sequencing with Pirtobrutinib and Other BTKs

This segment continues the deep dive into pirtobrutinib by examining how its performance compares with other BTKis, both covalent and non-covalent. Faculty discuss trial results showing that pirtobrutinib offers compelling efficacy in both treatment-naïve and relapsed patients, though treatment-naïve data remains early with incomplete follow-up. Although pirtobrutinib demonstrates noninferiority to ibrutinib, questions remain as to whether emerging trends in progression-free survival may eventually show differences as follow-up matures.

The conversation highlights pirtobrutinib’s standout cardiac safety profile, which aligns with earlier studies and makes it an attractive option for patients with atrial fibrillation risk, prior cardiac events, or multiple comorbidities. When comparing pirtobrutinib to second-generation covalent BTKis (acalabrutinib, zanubrutinib), clinicians note that all three are well-tolerated, though pirtobrutinib may have incremental advantages regarding cardiac events and hypertension. However, they caution against over-interpreting cross-trial comparisons.

The panel also explores clinical sequences that may be influenced by pirtobrutinib’s approval. In older or frail patients needing only one or two lifetime therapies, pirtobrutinib may move earlier because of its favorable safety. For most patients, however, clinicians still seek more long-term data before adopting pirtobrutinib as a frontline or second-line standard.

Finally, they address how time-limited BTKi-based strategies could reduce cumulative toxicity and minimize resistance development, which become critical considerations as more patients cycle through multiple lines of treatment. Although the usage of pirtobrutinib will increase, its precise placement in the treatment algorithm remains an active area of refinement.