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Pirtobrutinib Outperforms Ibrutinib on Response, Shows Early PFS Edge in First Head‑to‑Head CLL/SLL Trial

Fewer cardiovascular events bolster a favorable safety profile following the FDA’s conversion to full approval last week.

Overview

  • In the BRUIN CLL‑314 phase 3 trial, pirtobrutinib achieved a higher overall response rate than ibrutinib in the intent‑to‑treat population (87% vs 78.5%; P = .0035) and met its noninferiority primary endpoint.
  • Progression‑free survival remains immature but favored pirtobrutinib at 18 months in the intent‑to‑treat analysis (86.9% vs 82.3%; HR 0.57), with no overall survival differences reported.
  • The treatment‑naive cohort showed the strongest signal with higher 18‑month PFS (95.3% vs 87.6%; HR 0.24) and numerically higher response (92.9% vs 85.8%).
  • Safety findings included lower rates of atrial fibrillation/flutter (2.4% vs 13.5%) and hypertension (10.6% vs 15.1%) with pirtobrutinib, alongside fewer dose reductions, though neutropenia occurred more often.
  • Final phase 1/2 BRUIN results in patients previously treated with covalent BTK inhibitors reported an ORR of 81.6% and median PFS of 18.7 months, supporting the FDA’s December 3 move to full approval for CLL/SLL after covalent BTK therapy.