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

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.

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.

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.

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 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 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 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 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 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 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 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.