Jaypirca Significantly Improves PFS Outcomes in Untreated CLL/SLL

Treatment with Jaypirca (pirtobrutinib) monotherapy demonstrated a statistically significant and clinically meaningful improvement in progression-free survival compared with bendamustine plus Rituxan (rituximab; BR), according to results from the first phase 3 trial evaluating a noncovalent Bruton tyrosine kinase (BTK) inhibitor for treatment-naive chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

The results presented at the 67th ASH Annual Meeting indicate that Jaypirca reduced the risk of disease progression or death by approximately 80% versus standard chemoimmunotherapy. Investigators noted that the data support the agent as a potential new standard of care for untreated patients particularly older adults who may be limited to a single line of therapy.

“It was a knockout,” Dr. Wojciech Jurczak, Department of Clinical Oncology at the Maria Sklodowska-Curie National Research Institute of Oncology, in Poland, said during the presentation. “If we compare the similar comparisons of bendamustine, other BTK inhibitors like Imbruvica [ibrutinib] or Brukinsa [zanubrutinib], the hazard ratio is about 0.35.”

“Jaypirca was effective in whichever subgroup we analyzed,” she added.

Efficacy Outcomes Demonstrate Strong Disease Control With Jaypirca 

At the 24-month landmark, the progression-free survival rate was 93.4% for patients treated with Jaypirca versus 70.7% for those treated with BR. This benefit was consistent across key subgroups including patients with mutated IGHV and unmutated IGHV.

Although overall survival data remain immature, a notable trend favored the Jaypirca arm. The 24-month overall survival rate was 97.8% for the Jaypirca group compared with 90.8% for the BR group. This survival signal is particularly relevant given the high crossover rate allowed in the study design; 52.9% of patients in the BR arm crossed over to receive Jaypirca following confirmed disease progression.

Study Design Highlights Robust Comparison Against Chemoimmunotherapy 

The open-label phase 3 trial enrolled 282 patients with previously untreated CLL/SLL meeting International Workshop on Chronic Lymphocytic Leukemia 2018 criteria for therapy. Patients were randomized to receive oral Jaypirca once daily or up to six cycles of BR. Randomization was stratified by IGHV mutation status and Rai stage.

Key exclusion criteria included the presence of del(17p), known central nervous system involvement, Richter transformation or significant cardiovascular disease. The data cutoff for the current analysis was July 11, 2025.

Safety and Tolerability Profile Shows Lower Rates of Severe Side Effects 

Jaypirca exhibited a favorable safety profile consistent with previous reports in the relapsed/refractory setting. Despite a significantly longer median treatment duration for Jaypirca (32.3 months) compared with the fixed-duration BR regimen (5.6 months) the rate of severe side effects was lower in the experimental arm.

Grade 3 or higher treatment-emergent side effects occurred in 40% of patients receiving Jaypirca compared with 67.4% of those receiving BR. Furthermore, treatment discontinuation due to treatment-emergent side effects was significantly less frequent with Jaypirca (4.3%) than with BR (15.2%).

Specific side effects of interest for BTK inhibitors showed low incidence rates in the Jaypirca arm. Atrial fibrillation and atrial flutter (any grade) were reported in 1.4% of patients treated with Jaypirca compared with 0.7% in the BR arm. Among patients aged 75 years or older receiving Jaypirca, only 1 experienced atrial fibrillation or flutter. Rates of grade 3 or higher infections were also lower with Jaypirca (13.6%) compared with BR (57.1%) as were rates of grade 3 or higher neutropenia (7.1% versus 12.1%).

“Now, if we took this data together with the BRUIN CLL-314 study which was presented this conference where Jaypirca was opposed to Imbruvica and was also a positive study we can be optimistic about the approval of the compound possibly in early 2026,” concluded Jurczak.

References

1. “Pirtobrutinib vs bendamustine plus rituximab (BR) in patients with CLL/SLL: First results from a randomized phase III study Examining a non-covalent BTK inhibitor in untreated patients,” by Dr. Wojciech Jurczak. Blood.
2. “Pirtobrutinib vs ibrutinib in treatment-naïve and relapsed/refractory CLL/SLL: Results from the first randomized phase III study comparing a non-covalent and covalent BTK inhibitor,” by Dr. Wojciech Jurczak. Blood.

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