In a patient who has been receiving 1L Ibrutinib for TP53+ CLL for years with complete hematologic response but detectable MRD, is there any role to switch to the novel BTKi agents given better PFS?

There are a couple of features to this question that need comment. First, the goal of therapy with a single-agent BTKi, regardless of ibrutinib, acalabrutinib, zanubrutinib, or pirtobrutinib, is NOT to achieve undetectable MRD. Very few patients will achieve this milestone due to the drug's MOA. BTK...

In general, I have not switched patients who are responding well to ibrutinib to a second-generation covalent BTK inhibitor due to the concern for the potential to develop adverse events with a new treatment. Additionally, the role of MRD here is limited as there is no data to suggest that uMRD is p...

Although zanubrutinib was associated with superior PFS than ibrutinib in the ALPINE trial in the second-line setting (Brown et al., PMID 36511784), there are no clear data to suggest that changing from ibrutinib to a second-generation covalent BTKi would be beneficial for PFS, particularly in a pati...

In a patient with TP53-mutated CLL who has achieved a sustained clinical and hematologic remission on long-term ibrutinib, the presence of detectable MRD alone does not constitute an indication to change therapy. Covalent BTK inhibitors function as continuous disease-control agents and, as monothera...