Panelists discuss how future directions in chronic lymphocytic leukemia (CLL) treatment include promising developments with Bruton tyrosine kinase (BTK) degraders, noncovalent BTK inhibitors, alternative BCL2 inhibitors like sonrotoclax, bispecific antibodies for consolidation strategies, and addressing remaining gaps such as Richter transformation risk, infection susceptibility, and secondary malignancy surveillance in this rapidly evolving therapeutic landscape.
Panelists discuss how real-world evidence studies from databases like Flatiron demonstrate that second-generation Bruton tyrosine kinase (BTK) inhibitors perform better than first-generation agents in clinical practice, providing hypothesis-generating data that support clinical observations about treatment tolerability and infection rates, although these retrospective analyses should complement rather than replace randomized controlled trial evidence.
Panelists discuss how emerging combination strategies like acalabrutinib-venetoclax (AMPLIFY) and zanubrutinib-venetoclax (SEQUOIA Arm D) are expanding time-limited treatment options beyond the traditional venetoclax-obinutuzumab approach. However, they emphasize the need for longer follow-up data before widespread adoption and careful patient selection based on individual preferences and risk profiles.
Panelists discuss how to effectively mitigate Bruton tyrosine kinase (BTK) inhibitor toxicities through careful patient risk stratification, collaboration with cardio-oncologists, routine monitoring for arrhythmias and hypertension, appropriate use of dose reductions and drug holidays for chronic toxicities, and consideration of time-limited strategies to reduce long-term adverse effect exposure while maintaining treatment efficacy.
Panelists discuss how measurable residual disease (MRD) testing should be used primarily for prognostic information rather than routine treatment decision-making, with current guidelines recommending against using MRD results to alter therapy duration or change treatments. They question whether MRD negativity represents a sufficient surrogate end point for drug approvals, given the lack of cure potential and variable kinetics of MRD conversion.
Panelists discuss how obinutuzumab combinations with acalabrutinib (ELEVATE-TN data) and venetoclax (CLL14 data) provide compelling treatment options. The former shows continued progression-free survival benefits and curve separation over time, whereas the latter offers outstanding fixed-duration results even for high-risk patients. Both require careful consideration of intravenous (IV) vs oral preferences and long-term safety profiles.
Panelists discuss how the updated SEQUOIA Arm C data demonstrate that zanubrutinib monotherapy achieves a remarkable 72% progression-free survival at 5 years for high-risk patients with deletion 17p, showing similar outcomes to TP53 wild-type patients and establishing continuous monotherapy as an excellent option for these highest-risk patients.
Panelists discuss how to select among available Bruton tyrosine kinase (BTK) inhibitor treatment regimens for continuous vs fixed-duration strategies. They weigh the benefits of oral-only regimens against combination therapies that include intravenous (IV) infusions, while acknowledging the limited retreatment data for newer oral doublets.
Panelists discuss how the treatment landscape for treatment-naive patients with chronic lymphocytic leukemia (CLL) is rapidly evolving with new guideline updates every 6 to 12 months. They categorize approaches into fixed-duration vs continuous treatment strategies while emphasizing the need to study different molecular subtypes of CLL separately in future clinical trials.