A Patient-Centered Approach: Treatment Strategies for Progression and Intolerance in R/R CLL

Catherine Coombs, MD; John Allan, MD; and Joanna Rhodes, MD, MSCE, discuss how to treat patients with chronic lymphocytic leukemia (CLL) who develop high-risk disease features at relapse after initial venetoclax-based therapy. They cover treatment sequencing strategies, Bruton tyrosine kinase (BTK) inhibitor tolerability issues and switching approaches, retreatment considerations, and emerging therapies including chimeric antigen receptor (CAR) T-cell therapy and novel agents in development.

EP. 1: Clinical Perspectives: 59yF with R/R CLL After Time-Limited Therapy

May 27th 2025

Panelists discuss how a patient with CLL with initially low-risk disease and mutated IGHV unexpectedly relapsed early after receiving venetoclax-obinutuzumab treatment with acquisition of high-risk features, presenting unique treatment challenges.

EP. 2: Timing of Treatment Initiation in Relapsed CLL: Factoring in Prognostic and Patient Factors

May 27th 2025

Panelists discuss how they approach prognostic marker testing at relapse, the importance of ruling out Richter's transformation, and timing of treatment initiation based on disease characteristics and progression patterns.

EP. 3: Expert Perspectives: Sequencing Strategies After Acalabrutinib + Venetoclax +/- Obinutuzumab as First-Line Therapy in CLL

June 3rd 2025

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.

EP. 4: Clinical Perspectives: 59yF with R/R CLL Experiencing BTKi Treatment-Related AE

June 3rd 2025

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.

EP. 5: Considerations with Retreatment of Venetoclax-Containing Regimens

June 10th 2025

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.

EP. 6: Identifying BTKi Treatment Intolerance in R/R CLL

June 10th 2025

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.

EP. 7: Clinical Approaches in Switching Between BTKi’s in R/R CLL & Practical Considerations for Drug Holidays

June 17th 2025

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.

EP. 8: Expert Insights on BRUIN CLL-321: Pirtobrutinib in Patients With BTKi Pretreated CLL

June 17th 2025

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.

EP. 9: Real-World Clinical Practice Insights from the TRANSCEND CLL004 Trial

June 24th 2025

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.

EP. 10: Bridging Strategies to CAR T Therapy: Perspectives on Incorporating BTK Inhibitors

June 24th 2025

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.

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