PROs Remain Consistent During Pirtobrutinib Treatment for CLL/MCL

Treatment with pirtobrutinib (Jaypirca) led to consistent and stable patient-reported outcomes (PROs) over the course of therapy in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) or mantle cell lymphoma (MCL), according to a final analysis of the phase 1/2 BRUIN trial (NCT03740529).¹

Findings published in Current Medical Research and Opinion demonstrated that at a median follow-up of 46.5 months (IQR, 35.5-54.7) for patients with CLL/SLL (n = 263), improvement or stability in PROs from baseline to cycle 31 ranged from 83.1% to 94.1% for physical function, 88.0% to 94.7% for disease-related symptoms, 82.3% to 90.5% for fatigue, and 85.6% to 92.0% for global health status/quality of life (GHS/QOL). For evaluable patients with nonblastoid MCL (n = 124) at a median follow-up of 39.7 months (IQR, 27.8-45.0), PRO improvement or stability from baseline to cycle 20 was reported at ranges of 87.5% to 100.0% for physical function, 82.4% to 94.1% for disease-related symptoms, 70.6% to 94.1% for fatigue, and 82.2% to 95.0% for GHS/QOL.

“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,” lead study author Catherine C. Coombs, MD, and colleagues wrote in the publication of the data. “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.”

Coombs is an associate professor in the Division of Hematology-Oncology of the Department of Medicine at the University of California, Irvine School of Medicine.

What data were previously reported from the BRUIN trial?

In December 2023, the FDA granted accelerated approval to pirtobrutinib for the treatment of adult patients with CLL/SLL who have received at least 2 prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a BCL2 inhibitor, based on data from BRUIN.² Findings supporting the accelerated approval showed that evaluable patients treated with the noncovalent BTK inhibitor (n = 108) experienced an overall response rate (ORR) of 72% (95% CI, 63%-80%) and a median duration of response (DOR) of 12.2 months (95% CI, 9.3-14.7). Notably, in December 2025, the regulatory agency granted traditional approval to the agent for the treatment of patients with relapsed/refractory CLL/SLL who have been previously treated with a BTK inhibitor, based on data from the phase 3 BRUIN-CLL-321 trial (NCT04666038).³

Pirtobrutinib also holds accelerated approval for the treatment of patients with relapsed/refractory MCL after at least 2 lines of systemic therapy, including a BTK inhibitor.⁴ This regulatory decision was backed by data from BRUIN, which showed that evaluable patients (n = 120) achieved an ORR of 50% (95% CI, 41%-59%), including a complete response rate of 13%, and a median DOR of 8.3 months (95% CI, 5.7-not evaluable).

What was the design of BRUIN and the PRO analysis?

The open-label, multicenter BRUIN trial investigated pirtobrutinib monotherapy in patients with B-cell malignancies, including those with CLL/SLL who had received at least 2 prior lines of therapy and those with nonblastoid MCL who had received prior BTK inhibitor–based therapy.⁵

PRO end points were assessed via the EORTC QLQ-C30 (EORTC QLG Core Questionnaire). Patients completed PRO assessments at each study site visit, starting with the baseline evaluation on day 1 of cycle 1, with subsequent completions occurring in approximately 28-day intervals.¹

At the January 2025 data cutoff for the final PRO analysis, 39 of 263 patients with CLL/SLL remained on treatment with pirtobrutinib. Reasons for discontinuation included progressive disease (n = 141), adverse effects (AEs; n = 32), investigator decision (n = 8), concurrent illness (n = 6), patient withdrawal (n = 5), other (n = 13), study terminated (n = 1), and death (n = 18). In the CLL/SLL cohort, baseline mean PRO scores were 80.8 (SD, 19.5) for physical function, 24.7 (SD, 18.4) for CLL/SLL-related symptoms, 33.4 (SD, 24.7) for fatigue, and 61.6 (SD, 23.2) for GHS/QOL.

Among 124 patients with MCL, 9 remained on treatment at data cutoff. Discontinuation reasons comprised progressive disease (n = 81), AEs (n = 17), investigator decision (n = 4), patient withdrawal (n = 2), other (n = 3), and death (n = 8). Baseline mean PRO scores for the MCL group were 83.6 (SD, 18.0) for physical function, 21.2 (SD, 17.7) for MCL-related symptoms, 29.4 (SD, 23.3) for fatigue, and 62.6 (SD, 23.4) for GHS/QOL.

What additional outcomes were reported in the final PRO analysis?

Investigators reported no clear pattern in tumor response or in the proportion of patients with PRO improvements at the time of response or during treatment, due to small sample sizes of patients with stable or progressive disease.

The median time to worsening was not reached for all PRO end points due to low rates of death and worsening PROs. In the CLL/SLL group, data showed censoring rates of 76.9% for physical function, 78.8% for disease-related symptoms, 73.0% for fatigue, and 78.1% for GHS/QOL. For patients with MCL, censoring rates were 88.7% for physical function, 87.6% for disease-related symptoms, 85.7% for fatigue, and 84.0% for GHS/QOL.

References

1. 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
2. FDA grants accelerated approval to pirtobrutinib for chronic lymphocytic leukemia and small lymphocytic lymphoma. FDA. December 7, 2023. Accessed April 6, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pirtobrutinib-chronic-lymphocytic-leukemia-and-small-lymphocytic
3. FDA grants traditional approval to pirtobrutinib for chronic lymphocytic leukemia and small lymphocytic lymphoma. FDA. December 3, 2025. Accessed April 6, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-traditional-approval-pirtobrutinib-chronic-lymphocytic-leukemia-and-small-lymphocytic
4. FDA grants accelerated approval to pirtobrutinib for relapsed or refractory mantle cell lymphoma. FDA. January 27, 2023. Accessed April 6, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pirtobrutinib-relapsed-or-refractory-mantle-cell-lymphoma
5. A study of oral LOXO-305 in patients with previously treated CLL/​SLL or NHL. ClinicalTrials.gov. Updated January 27, 2026. Accessed April 6, 2026. https://clinicaltrials.gov/study/NCT03740529?viewType=Card&id=NCT03740529&rank=1