A Patient-Centered Approach: Treatment Strategies for Progression and Intolerance in R/R CLL - Episode 8
Expert Insights on BRUIN CLL-321: Pirtobrutinib in BTKi Pretreated CLL Patients
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.
Pirtobrutinib Trial Results and Second-Line Treatment Decisions
The BRUIN CLL-321 phase 3 trial demonstrated significant efficacy for pirtobrutinib in patients previously treated with covalent BTK inhibitors. The study showed superior progression-free survival compared to investigator's choice control arm, with median PFS of approximately 15 months versus 6-8 months for standard therapies. This landmark trial enrolled patients who were predominantly BTK inhibitor refractory (over 70%), yet pirtobrutinib achieved meaningful responses in this challenging population. The results support expanding pirtobrutinib's indication from third-line (post-BTK and BCL-2 inhibitor) to second-line (post-BTK inhibitor) therapy. The question of optimal second-line therapy choice between pirtobrutinib and venetoclax remains unanswered by comparative trial data. Treatment selection may depend on patient-specific factors including comfort with venetoclax ramp-up procedures, disease kinetics, and individual risk-benefit assessments, as both approaches offer valid second-line options.
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