Eli Lilly and Company has reported a major breakthrough in relapsed or refractory chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL).
The global pharma powerhouse has announced that its drug Jaypirca (pirtobrutinib) significantly improved outcomes when added to a standard time-limited regimen.
The Phase 3 BRUIN CLL-322 trial found that adding pirtobrutinib to venetoclax and rituximab reduced the risk of disease progression or death by 45% compared with venetoclax and rituximab alone, meeting its primary endpoint of progression-free survival.
“These results from BRUIN CLL-322 show that the addition of pirtobrutinib as part of a time-limited regimen further enhanced an already effective treatment and extended the duration of remission for patients with previously treated CLL.
"Importantly, the study provides the first robust evidence for such an approach in patients who received a prior BTK inhibitor,” said Matthew S. Davids, Chief of the Division of Lymphoma at Dana-Farber Cancer Institute.
He added: “Time-limited regimens are an important option in CLL care and provide patients with meaningful treatment-free intervals. In the context of the modern CLL treatment landscape, where many patients may only receive two lines of therapy, these results speak to the potential benefits that improving second-line therapy can have. Our study has the potential to establish a new standard of care in this population.”
The study enrolled 639 patients, nearly 80% of whom had previously received a covalent BTK inhibitor. Participants were randomly assigned to receive either the three-drug regimen of pirtobrutinib, venetoclax, and rituximab, or the two-drug control of venetoclax and rituximab.
At a median follow-up of 27.3 months, median progression-free survival was not reached in the pirtobrutinib arm versus 39.7 months in the control arm. The benefit was consistent across high-risk subgroups, including patients with TP53 mutations, 17p deletions, unmutated IGHV, and complex karyotypes.
In an exploratory analysis of second-line patients previously treated with a covalent BTK inhibitor, outcomes were particularly striking: median progression-free survival was not reached versus 28.3 months in the control arm, with a hazard ratio of 0.32.
“These remarkable findings support the potential addition of two years of Jaypirca to a time-limited venetoclax-based regimen in relapsed or refractory CLL,” said Jacob Van Naarden, executive vice president and president of Lilly Oncology.
Importantly, overall survival data remain immature, while time to next treatment also strongly favored the pirtobrutinib combination.
Safety findings were broadly consistent with known profiles of the individual drugs, with no major increase in toxicity seen with the addition of pirtobrutinib. Grade ≥3 adverse events were similar between groups (78.8% vs 73.0%), and discontinuation rates were nearly identical.
