Adherence, Treatment Discontinuation, and Planned BTK Inhibitor Holidays in Patients with CLL

Dr. Hoffmann frames long-term adherence as a practical challenge in continuous BTK inhibitor therapy. Dr. Coombs notes that time-limited therapy may offer adherence advantages through defined endpoints; she sees patients more frequently during venetoclax ramp-up due to cytopenia monitoring, enabling regular coaching toward completion. Continuous BTK inhibitor therapy without a defined endpoint can be psychologically challenging for patients, particularly younger, working patients.

Dr. Parikh emphasizes expanded treatment options have transformed the risk calculus, unlike the ibrutinib-only era when stopping therapy left few alternatives, today's landscape with multiple effective subsequent lines permits more thoughtful discontinuation decisions for patients with access issues or side effects. Practical adherence improvements include acalabrutinib's formulation change from capsule to tablet eliminating the PPI interaction concern, zanubrutinib's once-daily dosing option, and ongoing reductions in pill counts.

Dr. Shadman discusses planned elective BTK inhibitor discontinuation for patients in good clinical remission after at least 2 years of therapy. The ECOG study data suggest patients discontinuing ibrutinib for non-progression reasons achieved median PFS of approximately 27 months, providing some evidence that stopping after adequate exposure doesn't immediately compromise outcomes. He describes designing a SWOG cooperative group study of elective discontinuation versus continuation, using time to covalent BTK inhibitor failure (rather than PFS) as the primary endpoint, reasoning that PFS would necessarily favor continuous therapy but misses the patient-centric question of whether treatment holidays preserve ultimate covalent BTK inhibitor utility.

Consolidation off-trial is not recommended, but the planned study design allows clinician discretion about when to restart therapy, recognizing that requiring IWCLL-defined progression before restart may create patient discomfort, whereas waiting for very bulky disease is inappropriate.