INDIANAPOLIS, Indiana, June 14, 2026
Eli Lilly and Company announced compelling results from the pivotal Phase 3 BRUIN CLL-322 clinical trial, demonstrating that Jaypirca® (pirtobrutinib) combined with venetoclax and rituximab significantly improved outcomes for patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). The study met its primary endpoint, showing that the addition of Jaypirca reduced the risk of disease progression or death by 45% compared with venetoclax and rituximab alone. The findings, selected for a late-breaking oral presentation at the European Hematology Association (EHA) 2026 Annual Meeting, further strengthen the growing body of evidence supporting Jaypirca as a transformative therapy across the CLL treatment continuum. The results are particularly significant because the majority of enrolled patients had previously received a covalent BTK inhibitor, reflecting real-world treatment patterns and highlighting the regimen’s relevance in modern hematology practice.
Phase 3 BRUIN CLL-322 Trial Delivers Strong Efficacy Results
The global Phase 3 trial enrolled 639 patients with previously treated CLL or SLL and compared a regimen of Jaypirca, venetoclax, and rituximab (PVR) against venetoclax plus rituximab (VR). At a median follow-up of 27.3 months, patients receiving the Jaypirca combination achieved a statistically significant improvement in progression-free survival (PFS). Median PFS was not reached in the PVR arm, compared with 39.7 months in the control arm. Importantly, the clinical benefit remained consistent across multiple high-risk patient subgroups, including those with prior BTK inhibitor exposure, TP53 mutations, 17p deletions, unmutated IGHV status, and complex karyotypes.
Among second-line patients whose disease progressed after first-line BTK inhibitor therapy, the results were particularly impressive, with a hazard ratio of 0.32, indicating a substantial reduction in disease progression risk. Researchers noted that these findings represent the first Phase 3 study to demonstrate superiority over a venetoclax-containing control arm in CLL, potentially establishing a new treatment standard for relapsed disease.
Time-Limited Treatment Strategy Extends Remission Duration
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One of the most important aspects of the BRUIN CLL-322 study is its evaluation of a time-limited treatment approach, an increasingly attractive strategy for patients seeking durable disease control without indefinite therapy. Patients in the experimental arm received Jaypirca alongside a two-year venetoclax and rituximab regimen, resulting in deeper and longer-lasting remissions. Investigators emphasized that treatment-free intervals are highly valued in CLL care because they can improve quality of life while reducing long-term treatment burden.
Additional secondary analyses showed favorable trends for time to next treatment (TTNT), further supporting the regimen’s ability to delay disease progression and extend remission duration. Although overall survival data remain immature, early analyses suggested a positive trend favoring the Jaypirca combination, reinforcing optimism regarding its long-term clinical impact.
Safety Profile Supports Potential Regulatory Expansion
The safety profile observed in BRUIN CLL-322 was generally consistent with the established characteristics of the individual therapies, with minimal additive toxicity reported. Rates of severe adverse events were comparable between treatment groups, while discontinuation rates due to treatment-related side effects remained low. Researchers also observed favorable reductions in tumor lysis syndrome risk among patients receiving the Jaypirca-containing regimen. As a highly selective, non-covalent Bruton tyrosine kinase (BTK) inhibitor, Jaypirca continues to demonstrate versatility across multiple B-cell malignancies, including CLL and mantle cell lymphoma. Following these positive findings, Lilly plans to submit the BRUIN CLL-322 data to regulatory authorities worldwide in pursuit of expanded approvals. If approved, the regimen could redefine second-line treatment strategies and offer patients with relapsed or refractory CLL/SLL a powerful new option capable of delivering longer remissions and improved disease control.
Source: Eli Lilly press release
