While many CLL patients prefer fixed-duration therapy to avoid continuous medication, this preference is often overridden by practical logistics. The burden of increased monitoring and frequent clinic visits associated with fixed-duration regimens leads some patients to opt for continuous therapy instead.
Clinicians are hesitant to use newer, potentially safer non-covalent BTK inhibitors before established covalent inhibitors. While it's known that non-covalents work after covalents fail, the reverse is unproven, creating a one-way treatment path that reserves these newer agents for later lines of therapy.
With highly effective CLL therapies, primary causes of mortality are now infections and secondary cancers from immunodeficiency. Research is now focusing on immune reconstitution after treatment, marking a pivotal shift towards managing long-term survivorship challenges beyond just controlling the leukemia itself.
Recent non-inferiority trials affirm that fixed-duration combination therapies are viable alternatives to continuous BTK inhibitors. However, clinicians must look beyond the headline conclusion, as numerical data can show slightly worse progression-free survival for high-risk subgroups within the acceptable non-inferiority margin, complicating treatment decisions.
Although continuous BTK inhibitors have the most prospective data for high-risk CLL (17p/TP53 mutations), some highly motivated patients still opt for fixed-duration treatment. This requires a detailed conversation where clinicians must explain the trade-off: achieving a treatment-free period may come at the cost of needing second-line therapy sooner.