Lilly’s Jaypirca scores another Phase III win in CLL, but use with Venclexta still evolving in practice

Lilly's Jaypirca (pirtobrutinib) demonstrated a 45% reduction in the risk of disease progression or death when added to a venetoclax-rheux regimen in relapsed or refractory CLL/SLL in the Phase III BRUIN CLL-322 trial, marking Jaypirca’s fourth positive Phase III outcome in CLL and the first Phase III study to show superiority over a venetoclax-containing arm in this indication.

Jaypirca is currently approved as a single-agent therapy for adults with relapsed or refractory CLL/SLL who have previously been treated with a covalent BTK inhibitor, but the optimal positioning of the combination with venetoclax (timing, duration, and sequence of use) remains under discussion and not yet fully defined in clinical practice.

The BRUIN CLL-322 regimen added Jaypirca to a two-year venetoclax plus rituximab regimen, resulting in higher rates of progression-free survival and undetectable minimal residual disease, which strengthens the rationale for combining Jaypirca with venetoclax-based time-limited therapy, although long-term safety and real-world adoption patterns are still evolving.