Among patients in the relapsed/refractory and treatment-naive settings with Bruton tyrosine kinase inhibitor–naive chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL), Jaypirca (pirtobrutinib) worked as well as Imbruvica (ibrutinib) in shrinking or controlling cancer, according to updated data from the phase 3 BRUIN CLL-314 trial.
In this direct comparison, the data also suggested that patients taking Jaypirca showed a progression-free survival benefit, Dr. Jennifer Woyach reported when presenting the findings at the 2025 American Society of Hematology Annual Meeting.
In the intent-to-treat population of patients with either relapsed/refractory CLL or treatment-naive CLL, the overall response rate was 87% in patients randomized to Jaypirca (331 patients) versus 78.5% in those randomized to Imbruvica (331 patients). The best overall response with Jaypirca versus Imbruvica, respectively, was complete remission or complete remission with incomplete hematologic recovery of 4.8% versus 2.4%, partial remission or nodular partial remission of 82.2% versus 76.1%, partial remission with lymphocytosis of 2.4% versus 3.9%, stable disease of 5.4% versus 10.9%, and progressive disease of 1.5% versus 1.2%.
In the treatment-naive population, the overall response rate was 92.9% in patients randomized to Jaypirca (112 patients) versus 85.8% in those randomized to Imbruvica (113 patients). The best overall response with Jaypirca versus Imbruvica, respectively, was complete remission or complete remission with incomplete hematologic recovery of 7.1% versus 3.5%, partial remission or nodular partial remission of 85.7% versus 82.3%, partial remission with lymphocytosis of 0.9% versus 2.7%, stable disease of 2.7% versus 4.4%, and no cases of progressive disease.
In the relapsed/refractory population, the overall response rate was 84% in patients randomized to Jaypirca (219 patients) versus 74.8% in those randomized to Imbruvica (218 patients). The best overall response with Jaypirca versus Imbruvica, respectively, was complete remission or complete remission with incomplete hematologic recovery of 3.7% versus 1.8%, partial remission or nodular partial remission of 80.4% versus 72.9%, partial remission with lymphocytosis of 3.2% versus 4.6%, stable disease of 6.8% versus 14.2%, and progressive disease of 2.3% versus 1.8%.
“Jaypirca demonstrated consistently higher overall response rates than Imbruvica across all patients including treatment-naive and relapsed/refractory populations,” said Woyach, director of the Division of Hematology at The Ohio State University Comprehensive Cancer Center.
Progression-free survival data, although immature, showed a trend in favor of Jaypirca. In the intent-to-treat population, at a median follow-up of 22 months with Jaypirca and 19.7 months with Imbruvica, the 18-month progression-free survival rates per investigator assessment were 86.9% versus 82.3%. In the relapsed/refractory population, at a median follow-up of 18.4 months with Jaypirca and 15.8 months with Imbruvica, the investigator-assessed 18-month progression-free survival rates were 81.7% versus 79.2%. In the treatment-naive population, at a median follow-up of 22.5 months with Jaypirca and 22.4 months with Imbruvica, the investigator-assessed 18-month progression-free survival rates were 95.3% versus 87.6%.
“Early trends in progression-free survival favored Jaypirca among all patients and in the relapsed/refractory and treatment-naive populations,” said Woyach, adding that the most pronounced effect occurred in the treatment-naive population, which had the longest follow-up at this data cutoff.
Understanding the Safety of Jaypirca in CLL Treatment
Regarding safety, the most common all-grade treatment-emergent side effects with Jaypirca versus Imbruvica were neutropenia (22.7% versus 17.8%), upper respiratory tract infection (17.9% versus 19.4%), anemia (15.2% versus 14.2%), pneumonia (13.6% versus 15.1%), and diarrhea (13.3% versus 19.1%). The most common grade 3 or higher treatment-emergent side effects with Jaypirca versus Imbruvica were neutropenia (17.3% versus 13.2%), pneumonia (6.4% versus 8.6%), and anemia (5.8% versus 3.7%).
Rates of all-grade (10.6% versus 15.1%) and grade 3 or higher (3.3% versus 4.9%) hypertension were lower with Jaypirca versus Imbruvica. One patient developed Richter transformation with Jaypirca versus 4 patients with Imbruvica.
“Jaypirca was well tolerated with fewer dose reductions and discontinuations due to treatment-emergent side effects than Imbruvica,” Woyach said.
She noted that side effects of special interest were mostly low-grade and consistent with prior Jaypirca studies. Grade 3 or higher neutropenia (25.2% versus 17.5%) and anemia (6.1% versus 3.7%) were higher with Jaypirca versus Imbruvica; however, grade 3 or higher thrombocytopenia was lower with Jaypirca (3.6% versus 4%).
All-grade atrial fibrillation or flutter (2.4% versus 13.5%) was substantially lower with Jaypirca versus Imbruvica, particularly among patients aged 75 years or older (4.5% versus 21.4%).
Study Design for the Phase 3 BRUIN CLL-314 Trial and Patient Characteristics
The phase 3 BRUIN CLL study accrued patients with Bruton tyrosine kinase inhibitor–naive CLL/SLL, including both treatment-naive and relapsed/refractory disease. Overall, 662 patients (intent-to-treat population) were randomized to Jaypirca (331 patients) or Imbruvica (331 patients) between August 18 2022 and June 17 2024. The median age was 67 years in both arms and the median number of prior therapies in both arms was 1. In the intent-to-treat population, 225 patients were treatment-naive and 437 patients were relapsed/refractory.
In patients with evaluable samples, 68% (199 of 293 patients) versus 66% (183 of 277 patients) in the Jaypirca versus Imbruvica cohorts had unmutated IGHV. Additionally, 40% (104 of 259 patients) versus 34% (78 of 227 patients) and 15% (50 of 331 patients) versus 16% (52 of 331 patients) had complex karyotype with 3 or more abnormalities and del(17p), respectively.
Jaypirca was administered orally at 200 mg daily and Imbruvica was administered orally at 420 mg daily. The primary end point was non-inferiority of overall response rate in the intent-to-treat population or relapsed/refractory population. The key secondary end point was superiority of progression-free survival in the intent-to-treat population or relapsed/refractory population.
What is the Significance the Phase 3 BRUIN CLL-314 Trial?
This study is the first to compare Jaypirca and Imbruvica in treatment-naive patients and patients with Bruton tyrosine kinase inhibitor-naive relapsed/refractory CLL/SLL.
Jaypirca is currently approved by the FDA for patients with relapsed/refractory CLL/SLL who have previously received a Bruton tyrosine kinase inhibitor. When the progression-free survival data from the BRUIN CLL study fully mature, it is hoped that the trend favoring Jaypirca will be upheld and can support a regulatory filing for use in earlier CLL/SLL treatment lines.
References
- “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. Jennifer Woyach, et al. Blood.
- “FDA grants traditional approval to pirtobrutinib for chronic lymphocytic leukemia and small lymphocytic lymphoma,” by U.S. Food and Drug Administration. News release; Dec. 3, 2025.
- FDA Approves Jaypirca for Relapsed/Refractory CLL or SLL, by Alex Biese. CURE; Dec. 3, 2025. https://www.curetoday.com/view/fda-approves-jaypirca-for-r-r-cll-or-sll
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