Resistance Testing, Peripheral vs. Tissue Sampling, and Clinical Monitoring

This segment explores the expanding but nuanced role of molecular resistance testing in CLL. The panel discusses how BTK and BCL2 resistance mutations influence therapeutic decisions and whether such testing should be performed routinely in clinical practice. They emphasize that while mutation information is highly informative in clinical trials, its real-world impact on decision-making varies based on urgency, available agents, and disease symptoms.

A major focus is where testing should be performed: peripheral blood, bone marrow, or lymph node biopsy. Most experts agree that peripheral blood is sufficient in the majority of cases, as it is minimally invasive, easily repeated, and usually reflective of systemic disease biology. However, they acknowledge occasional discordances: a patient may have lymph node progression without detectable peripheral mutations, prompting consideration of tissue biopsy in select situations. They also note that known resistance-associated mutations explain only a portion of relapses; many cases progress without identifiable BTK or BCL2 mutations, underscoring gaps in current understanding of resistance biology.

The panel also touches on clinical monitoring strategies, including when to intervene during biochemical or imaging-defined progression. They caution against relying solely on molecular markers without clinical context and emphasize timely recognition of progression to open the window for appropriate treatments such as CAR-T, clinical trials, or cellular therapies.

This segment underscores the importance of personalized, context-driven use of molecular testing, which is valuable but not universally required, and highlights the need for future research to better define resistance pathways.