Andrew H Lipsky, MD

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.

Andrew Lipsky, MD, discusses data with pirtobrutinib in relapsed/refractory CLL and the effect of its FDA approval on sequencing decisions for this disease.