Phase 1/2 BRUIN: Pirtobrutinib Maintains Patient-Reported Outcomes in CLL/SLL and MCL

Key Highlights

• The final PRO analysis included 263 patients with CLL/SLL and 124 patients with non-blastoid MCL who received pirtobrutinib monotherapy after prior covalent BTK inhibitor therapy.
• More than 80% of patients with CLL/SLL had stable or improved physical function, disease-related symptoms, fatigue, and global health status/quality of life through Cycle 31.
• More than 70% of patients with MCL had stable or improved outcomes across similar PRO domains through Cycle 20.
• Median time to worsening was not reached in either cohort because of low rates of PRO worsening or death events.

Most patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) or mantle cell lymphoma (MCL) reported stable or improved patient-reported outcomes (PROs) during treatment with pirtobrutinib monotherapy in the final analysis of the phase 1/2 BRUIN trial, according to findings published in Current Medical Research and Opinion.

The analysis evaluated PROs among patients with B-cell malignancies treated with pirtobrutinib after prior covalent Bruton tyrosine kinase inhibitor (BTKi) exposure. Longitudinal analyses showed statistically significant and clinically meaningful improvement from baseline across key PRO domains in patients with CLL/SLL, while PRO assessments remained generally stable over time in patients with MCL.

BRUIN was an open-label, multicenter, phase 1/2 study of pirtobrutinib monotherapy for B-cell malignancies, including CLL/SLL and non-Hodgkin lymphoma, including MCL. The final PRO analysis included patients with CLL/SLL who had received at least 2 prior lines of therapy, including a covalent BTKi-containing regimen, and patients with non-blastoid MCL after prior covalent BTKi-based therapy.

PROs were collected using paper forms at each study visit, beginning at Cycle 1 Day 1 before study drug administration. Instruments included the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30, item library sets for CLL/SLL- and MCL-related symptoms, and an Expanded Fatigue measure. Prespecified analyses included descriptive change from baseline, time to worsening using the Kaplan-Meier method, and longitudinal analyses using a mixed model for repeated measures.

Study Findings

The final PRO analysis included 263 patients with CLL/SLL and prior covalent BTKi exposure, with a median follow-up of 46.5 months from study enrollment. At the January 27, 2025, data cutoff, 39 patients with CLL/SLL remained on study. Baseline PRO completion in the CLL/SLL cohort was 82.1%, and data were available for the most patients at alternating visits until Cycle 31, when 95 patients, or 36.1% of those enrolled, remained on treatment.

The MCL cohort included 124 patients with non-blastoid MCL, with a median follow-up on study of 39.7 months. At the data cutoff, 9 patients with MCL remained on study. By Cycle 20, 23 patients, or 18.5%, remained on study; PRO data were not reported beyond that point because insufficient patients remained on treatment to permit data collection.

At baseline, mean scores among patients with CLL/SLL were 80.8 for physical function, 24.7 for CLL/SLL-related symptoms, 33.4 for fatigue, and 61.6 for global health status/quality of life (GHS/QoL). Among patients with MCL, baseline mean scores were 83.6 for physical function, 21.2 for MCL-related symptoms, 29.4 for fatigue, and 62.6 for GHS/QoL.

Among patients with CLL/SLL, the proportion who improved or remained stable from baseline through Cycle 31 ranged from 83.1% to 94.1% for physical function, 88.0% to 94.7% for CLL/SLL-related symptoms, 82.3% to 90.5% for fatigue, and 85.6% to 92.0% for GHS/QoL. Longitudinal analyses in the CLL/SLL cohort consistently met statistically significant and clinically meaningful improvement thresholds from baseline for physical function, CLL/SLL-related symptoms, fatigue, and GHS/QoL.

Among patients with MCL, the proportion who improved or remained stable from baseline through Cycle 20 ranged from 87.5% to 100.0% for physical function, 82.4% to 94.1% for MCL-related symptoms, 70.6% to 94.1% for fatigue, and 82.2% to 95.0% for GHS/QoL. PRO assessments in the MCL cohort generally remained stable over time. Median time to worsening was not reached for any PRO endpoint in either cohort.

Clinical Implications

According to the study authors, the findings suggest that PROs remained stable throughout pirtobrutinib treatment and that most patients with CLL/SLL and MCL reported stable or improved outcomes during the study. The authors stated that the maintenance and improvement of quality of life are important for patients with CLL/SLL or MCL and that PRO data can help support shared treatment decision-making.

The study authors noted that the small MCL cohort, combined with low rates of data collection at some clinic visits, limited definitive conclusions and meant that MCL findings should not be overinterpreted. They also noted that fewer patients were available for PRO assessment over time as patients discontinued study treatment, limiting interpretation of longer-term PRO outcomes during treatment.

Expert Commentary

“It is imperative that PRO data are collected and disseminated so that patients and their providers can have a complete body of information to inform shared treatment decision making across all therapies available for patient care,” the researchers concluded. “The maintenance and improvement of quality of life is extremely important for patients with CLL or MCL. This study adds to the body of knowledge regarding patient experience while receiving pirtobrutinib, and continues to show the stable and improved outcomes that patients can expect following treatment initiation.”

Reference
Coombs CC, Woyach JA, Brown JR, et al. Patient-reported outcomes among patients with mantle cell lymphoma or chronic lymphocytic leukemia receiving pirtobrutinib in the BRUIN phase 1/2 study: final analysis. Curr Med Res Opin. 2025;41(12):2323-2338. doi:10.1080/03007995.2025.2607542