Catherine C. Coombs, MD

The panel addresses two important areas not fully covered earlier.

The panel emphasizes MRD testing is not a current standard of care requirement, advising community oncologists not to feel obligated to order it outside clinical trials or high-risk treatment extension decisions.

Dr. Lipsky outlines different conceptual frameworks for evaluating the 2 CELESTIAL trials.

Dr. Shadman introduces sonrotoclax as a next-generation selective BCL-2 inhibitor approved for mantle cell lymphoma, with emerging CLL data in combination with zanubrutinib.

Dr. Coombs frames sequencing philosophy around patient age and disease trajectory.

Dr. Parikh summarizes the CLL17 trial: a 3-arm comparison of continuous ibrutinib, ibrutinib-venetoclax doublet, and venetoclax-obinutuzumab, all with approximately 3-year median follow-up showing no significant PFS difference between fixed-duration regimens and continuous ibrutinib.

Dr. Hoffmann frames long-term adherence as a practical challenge in continuous BTK inhibitor therapy.

Dr. Lipsky separates high-risk biomarkers conceptually, emphasizing TP53 aberrations and IGHV unmutated status should be considered distinctly rather than aggregated. TP53 aberrations—encompassing del(17p) and/or TP53 mutation—represent the highest-risk adverse predictive biomarkers across all CLL treatment strategies.

Dr. Shadman reviews SEQUOIA 6-year follow-up data, highlighting that zanubrutinib monotherapy continues demonstrating high efficacy regardless of del(17p) status. Key outcomes include 74% PFS at 6 years for del(17p)-negative patients (Arm A) and 64% for del(17p)-positive patients (Arm C, 111 patients representing the largest prospective BTK inhibitor cohort in this high-risk population).

Dr. Parikh highlights the CLL14 9-year follow-up data as among the most important datasets presented at EHA 2026. The study enrolled treatment-naïve patients with significant comorbidities (high CIRS score) randomized to venetoclax-obinutuzumab versus chlorambucil-obinutuzumab. With 9-year follow-up, the median PFS for venetoclax-obinutuzumab reaches approximately 6 years overall, with a remarkably striking finding for IGHV-mutated patients achieving median PFS of approximately 8.5 to 9 years.

Dr. Marc Hoffmann introduces the program on optimizing CLL treatment strategies, noting that CLL remains the most common adult leukemia in the Western world with approximately 20,000 new annual US diagnoses. The panel includes Drs. Catherine Coombs, Andrew Lipsky, Sameer Parikh, and Mazyar Shadman.

Experts discuss advancements in CLL treatment, highlighting pirtobrutinib's role and the potential of CAR T-cells and bispecific therapies.

Experts discuss the role of MRD testing in CLL treatment, emphasizing personalized approaches and the importance of continuity in patient care.

Experts discuss the impact of real-world data on CLL treatment sequencing, highlighting survival outcomes and the importance of targeted therapies.

Explore the latest insights on venetoclax retreatment effectiveness and its impact on patient outcomes in chronic lymphocytic leukemia therapy.

Experts discuss the implications of recent studies on pirtobrutinib, comparing its efficacy and safety against other BTK inhibitors for CLL treatment.

Experts discuss strategies for selecting second-line therapies in CLL, emphasizing treatment history, patient response, and genetic factors.

Experts discuss the balance of safety, efficacy, and logistics in treatment choices, highlighting the evolving landscape of BTK inhibitors and patient preferences.

Experts discuss the importance of patient-specific factors and preferences in selecting first-line treatments for CLL.

Experts discuss evolving treatment strategies for CLL, highlighting the balance between time-limited and continuous therapies for optimal patient outcomes.

Explore the evolving treatment landscape for Chronic Lymphocytic Leukemia, focusing on BTK and BCL2 inhibitor strategies and biomarker testing insights.

Panelists discuss how emerging therapies including BTK degraders, bispecific antibodies, and novel BCL-2 inhibitors represent exciting future treatment options for managing CLL patients across different lines of therapy.

Panelists discuss how bridging therapy with BTK inhibitors may optimize CAR T-cell outcomes by controlling bulky disease during manufacturing, with ibrutinib showing specific benefits for T-cell function enhancement.

Panelists discuss how lisocabtagene maraleucel (liso-cel) CAR T-cell therapy shows promise in heavily pretreated CLL patients, particularly younger patients with high-risk disease features who can achieve durable remissions.

Panelists discuss how the positive BRUIN CLL-321 phase 3 trial results support pirtobrutinib use after covalent BTK inhibitor exposure and consider its role in second-line versus third-line treatment sequencing.

Panelists discuss how clinical trial data supports switching between different covalent BTK inhibitors for intolerance management, with 60-70% of patients experiencing resolution of the original toxicity.

Panelists discuss how to define true BTK inhibitor intolerance versus manageable side effects and describe successful strategies for switching between covalent BTK inhibitors to maintain treatment efficacy.

Panelists discuss how retreatment with venetoclax may be appropriate in certain scenarios despite prior exposure, though continuous BTK inhibitor therapy is often preferred for patients with high-risk disease features.

Panelists discuss how to manage BTK inhibitor-related adverse events including atrial fibrillation, bleeding, and gastrointestinal toxicities through dose modifications, supportive care, and potential drug switching strategies.

Panelists discuss how sequencing therapies becomes challenging when using combination regimens like acalabrutinib-venetoclax in frontline treatment, requiring careful consideration of retreatment strategies and resistance mutation testing.