News
Article
Jaypirca showed superior progression-free survival and lower discontinuation rates versus standard treatments in patients with previously treated CLL or SLL.
Treatment with Jaypirca was shown to reduce treatment discontinuations in patients with CLL or SLL.
Among patients with previously treated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), Jaypirca (pirtobrutinib) demonstrated superior progression-free survival (PFS) and low rates of treatment discontinuation versus the investigator’s choice of treatment, according to findings from the prospective phase 3 BRUIN CLL-321 trial, presented at the 2024 ASH Annual Meeting.
In the study, patients with CLL or SLL were randomly assigned to receive Jaypirca monotherapy (119 patients) or Zydelig (idelalisib) plus Rituxan (rituximab) or bendamustine plus Rituxan (119 patients; IdelaR/BR). The primary end point was PFS and was met at the trial’s primary analysis in August 2023. The secondary end point was overall survival (OS) with a final analysis in August 2024.
At a median follow-up of 19.4 months, patients in the Jaypirca group had a median PFS of 14 months. At a median follow-up of 17.7 months, patients in the idelaR/BR group had a median PFS of 8.7 months. The independent review committee (IRC) reported that Jaypirca reduced the risk of progression or death by 46%.
Event-free survival (EFS): time until a patient experiences disease progression, death or a specific event.
Progression-free survival (PFS): time until a patient's disease worsens or death.
Overall survival (OS): time a patient lives after a diagnosis, regardless of disease status, until death by any cause.
The investigator-assessed PFS showed that at a median follow-up of 19.4 months, median PFS was 15.3 months in the treatment group versus 9.2 months in the control group at a median follow-up of 17.5 months. Jaypirca reduced the risk of progression or death by 52% in the investigator assessment.
“The investigator assessment of PFS was consistent with the independent review committee,” Dr. Jeff P. Sharman, director of research, Williamette Valley Cancer Institute, and medical director of hematology research at the US Oncology Network, in Eugene, Oregon, said during a presentation of the data at the meeting.
The safety profile for the Jaypirca was consistent with prior phase 1 and 2 trials. Treatment-related side effects led to discontinuation in 5.2% of patients who received Jaypirca versus 21.1% among patients who received IdelaR/BR treatment. When adjusting for exposure, the incidence rate of treatment-emergent side effects was lower with Jaypirca compared with IdelaR/BR.
Investigators also evaluated side effects of special interest (AESI) that are common to BTK inhibitors. Any-grade hypertension was reported in 6.9% of patients and grade 3 (severe) or worse was reported in 2.6% of patients. “Although patients with atrial arrhythmias were not excluded from the trial, cumulative event rates were low,” Sharman said. “Furthermore, two of the three subjects with treatment emergent atrial fibrillation had a prior history,” he continued.
Jaypirca was also favored in event-free survival (EFS). At a median follow-up of 19.4 months, the experimental group had a median EFS of 14.1 months versus 7.6 months in the control group at a median follow-up of 18.7 months. Jaypirca reduced the risk of an event by 61%.
“The event-free survival end point captures not only progression and death, but also discontinuations for toxicity, and thus better captures the integrated efficacy and safety of the intervention,” Sharman said.
The time to next treatment (TTNT) or death was also evaluated. At a median follow-up of 20 months, the experimental group demonstrated a median TTNT of 24 months versus 10.9 months in the control group at a median follow-up of 20.2 months. Jaypirca reduced the risk of starting next treatment or death by 63% with a median TTNT of about 24 months. “This captures the overall efficacy of the treatment as patients with IRC-determined asymptomatic radiographic progressions who are benefitting from therapy were not mandated to discontinue treatment,” Sharman said.
When TTNT was stratified by prior exposure to Venclexta (venetoclax), patients who received Jaypirca but were naïve to the BCL2 inhibitor (59 patients/group) had a median TTNT of 29.5 months versus 12.5 months for those who received IdelaR/BR. In patients who were previously treated with venetoclax (60 patients/group), the median TTNT was 20 months in the treatment group versus 8.7 months in the control group.
“[Jaypirca] was able to delay subsequent treatment or death for 2.5 years in patients who were naive to venetoclax, demonstrating that continued BTK inhibition can be an effective strategy after failure of first- or second-generation BTK agents,” Sharman said.
Although OS was evaluated, the study was not powered to detect the difference between the two groups, noted Sharman. Further, the analysis was confounded because 76% of patients were allowed to cross over post-progression.
PFS among clinical subgroups also demonstrated a consistent benefit in favor of Jaypirca and this was observed across molecular characteristics, including TP53 status, complex karyotype and IGHV status.
“[Jaypirca] is an effective, well-tolerated agent in patients with difficult-to-treat disease and provides a clinically meaningful way to sustain BTK inhibition,” Sharman concluded.
Reference
“BRUIN CLL-321: Randomized phase III trial of Jaypirca versus idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR) in BTK inhibitor pretreated chronic lymphocytic leukemia/small lymphocytic lymphoma” By Dr. Sharman JP, et al., Blood.
For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.
