My Treatment Approach: Shared Decision-Making in CLL: Balancing Safety, Efficacy, and Patient Preference in CLL

John Allan, MD; Susan O’Brien, MD; and Javier Pinilla, MD, PhD, discuss how shared decision-making in chronic lymphocytic leukemia (CLL) treatment involves balancing Bruton tyrosine kinase (BTK) inhibitor safety profiles, efficacy data, and patient preferences when choosing among continuous monotherapy, fixed-duration combinations, and managing treatment-related adverse events through dose modifications and multidisciplinary care approaches.

EP. 1: Clinical Perspectives: BTKi Treatment-Related Adverse Effects in Relapsed CLL

July 30th 2025

Panelists discuss how shared decision-making approaches in CLL treatment should balance BTKi selection with patient-specific risk features, particularly emphasizing the preference for BTKis over venetoclax-based therapy in high-risk patients with 17p deletion, while noting that approximately 20% of patients still receive outdated chemoimmunotherapy despite newer targeted treatments being available since 2016.

EP. 2: Identifying the Appropriate Patient With CLL for Continuous BTKi vs Fixed Duration BTKi + BCL-2i Regimens

July 30th 2025

Panelists discuss how treatment selection in CLL has evolved from universal single-agent BTKi use to a more personalized approach that considers patient-specific factors like IGHV mutation status, TP53 mutations, and 17p deletions, with growing excitement about emerging fixed-duration oral doublet therapies combining BTKis with BCL-2 inhibitors that may offer superior efficacy while reducing long-term toxicities and financial burden compared with continuous monotherapy approaches.

EP. 3: Expert Insights: Exploring Efficacy Differences in CLL MRD Rates Between the Fixed-Duration BTKi + BCL2i Regimens

August 6th 2025

EP. 4: Identifying BTKi Treatment-Related Adverse Events

August 6th 2025

Panelists discuss how CLL treatment has evolved from universal single-agent BTKi use to personalized approaches based on patient risk factors like IGHV mutation status and TP53 mutations, with growing excitement about fixed-duration oral doublet therapies combining BTKis with venetoclax that show promising efficacy despite lower MRD rates compared with antibody-containing regimens, while addressing the management of BTKi class effects including cardiovascular events, hypertension, bleeding, diarrhea, and rash that typically occur early in treatment but can sometimes develop later, with dose-reduction strategies being effective for maintaining efficacy while managing tolerability across first- and second-generation BTKis.

EP. 5: Clinical Practice Insights: Comparing the Safety Profiles of Acalabrutinib, Ibrutinib, and Zanubrutinib

August 13th 2025

Panelists discuss how CLL treatment has evolved from universal single-agent BTKi use to personalized approaches based on patient risk factors like IGHV mutation status and TP53 mutations, with growing excitement about fixed-duration oral doublet therapies combining BTKis with venetoclax that show promising efficacy despite lower MRD rates compared with antibody-containing regimens, while addressing the management of BTKi class effects including cardiovascular events, hypertension, bleeding, diarrhea, and rash that typically occur early in treatment, noting that while second-generation BTKis may have slightly improved tolerability profiles compared with ibrutinib, most annoying adverse effects like arthralgias, cramps, and fatigue develop tachyphylaxis over time, with bleeding complications and late-onset dyskinesias being among the most challenging adverse events to manage across all BTKis.

EP. 6: BTKi Dose Modification: Preserving Efficacy While Managing Toxicity in CLL Therapy

August 13th 2025

Panelists discuss how chronic lymphocytic leukemia treatment has evolved from universal single-agent BTKi use to personalized approaches based on patient risk factors like IGHV mutation status and TP53 mutations, with growing excitement about fixed-duration oral doublet therapies combining BTKis with venetoclax that show promising efficacy despite lower MRD rates compared with antibody-containing regimens, while addressing the management of BTKi class effects including cardiovascular events, hypertension, bleeding, diarrhea, and rash through dose-modification strategies that have become preferred over drug switching, particularly for ibrutinib, where robust long-term data support maintained efficacy with dose reductions from 420 mg to 280 mg daily, though similar dose reduction evidence is less established for second-generation BTKis like acalabrutinib and zanubrutinib.

EP. 7: Coordinating CLL Care to Identify BTKi Intolerance and Manage Toxicities

August 20th 2025

Panelists discuss how CLL treatment has evolved from universal single-agent BTKi use to personalized approaches based on patient risk factors like IGHV mutation status and TP53 mutations, with growing excitement about fixed-duration oral doublet therapies combining BTKis with venetoclax that show promising efficacy despite lower MRD rates compared with antibody-containing regimens, while addressing the management of BTKi class effects through dose-modification strategies that have become preferred over drug switching, emphasizing that intolerance is subjectively defined by patient acceptance and requires a multidisciplinary team approach including extensive patient education, close monitoring by nurses and pharmacists, and collaboration with cardio-oncology specialists to manage cardiovascular toxicities, with the notable exception that ventricular arrhythmias like PVCs warrant immediate consideration for drug discontinuation due to risk of sudden death.

EP. 8: ASH 2025 Data Watch: Anticipated Developments for the CLL Treatment Landscape

August 20th 2025

Panelists discuss how CLL treatment has evolved from universal single-agent BTKi use to personalized approaches based on patient risk factors like IGHV mutation status and TP53 mutations, with growing excitement about fixed-duration oral doublet therapies combining BTKis with venetoclax that show promising efficacy despite lower MRD rates compared with antibody-containing regimens, while addressing the management of BTKi class effects through dose-modification strategies and multidisciplinary care coordination, and anticipating future developments including BTK degraders that show excellent efficacy with improved safety profiles in highly refractory populations, bispecific antibodies for fixed-duration approaches, and results from the CLL17 trial comparing oral doublets to venetoclax-obinutuzumab that may further establish the role of time-limited combination therapies in transforming the treatment landscape.