Optimizing Treatment Strategies for Patients with CLL

Panelist discusses how frontline CLL treatment has evolved from choosing between continuous oral therapy vs fixed-duration combination therapy to now including new all-oral fixed-duration regimens, explaining the advantages and disadvantages of each approach based on patient preferences.

Panelist discusses how patient preference significantly impacts treatment selection and describes the process of involving patients in treatment decisions while considering disease characteristics, cytogenetics, and the fact that higher-risk patients may fare better with specific regimens.

Panelist discusses how the SEQUOIA study demonstrated that zanubrutinib monotherapy maintains excellent progression-free survival in patients with high-risk chronic lymphocytic leukemia with TP53 mutation or 17p deletion, providing a valuable treatment option for this difficult-to-treat population.

Panelist discusses how efficacy and safety data from trials like ELEVATE-TN and CLL14 inform treatment decisions, noting that while both regimens are effective, patients with 17p deletion tend to respond better to Bruton tyrosine kinase inhibitors than fixed duration venetoclax combinations.

Panelist discusses how minimal residual disease testing serves as an important tool for guiding treatment decisions in fixed-duration therapy, though standardization of testing methods and interpretation remains challenging in real-world practice.

Panelist discusses how managing toxicities requires understanding different safety profiles of novel agents, considering long-term effects like infection risk and secondary malignancies, and selecting therapies based on individual patient comorbidities and quality of life factors.

Panelist discusses how new all-oral combination regimens are transforming the treatment landscape by addressing unmet needs in patients with high-risk chronic lymphocytic leukemia, particularly those with TP53 mutations and 17p deletions, while considering factors like cost, adverse effects, and patient-specific characteristics.

Panelist discusses how Bruton tyrosine kinase inhibitors fit into real-world practice with community physicians often using monotherapy, while emphasizing the importance of specialist knowledge to optimize combination therapy selection and considering infection risks in different treatment eras.

Panelist discusses how recent ASCO updates, particularly the SEQUOIA study results, highlight the long-term efficacy of zanubrutinib in high-risk patients and represent the most significant advances in CLL treatment from the meeting.

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.

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 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 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 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 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 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 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 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.