Pirtobrutinib Demonstrates Durable Clinical Activity in Relapsed or Refractory Marginal Zone Lymphoma
Clinical Summary:
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Design/Population: This phase 1/2 BRUIN analysis evaluated pirtobrutinib in heavily pretreated patients with relapsed or refractory marginal zone lymphoma, most of whom had previously received anti-CD20 therapy, chemotherapy, and covalent Bruton tyrosine kinase inhibitors (BTKis).
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Key Outcomes: Pirtobrutinib achieved an objective response rate of 55.6%, with durable responses and a median progression-free survival of 16.6 months. Clinical activity was maintained among patients previously treated with covalent BTK inhibitors, and the safety profile was consistent with previous reports.
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Clinical Relevance: These findings support pirtobrutinib as a potential treatment option for patients with relapsed or refractory marginal zone lymphoma, including those previously treated with covalent BTK inhibitors, and warrant continued evaluation of noncovalent BTK inhibition in this setting.
Results from the phase 1/2 BRUIN study demonstrated that pirtobrutinib, a highly selective, noncovalent Bruton tyrosine kinase inhibitor (BTKi), produced durable clinical activity with a manageable safety profile in heavily pretreated patients with relapsed or refractory marginal zone lymphoma, including those previously treated with covalent BTKis.
“For systemic disease, available first-line therapies include anti-CD20 antibody as monotherapy with or in combination with chemotherapy (chemoimmunotherapy), with second-line options such as [cBTKIs]...however, management of relapsed and refractory [disease] remains a challenge,” stated Krish Patel, MD, Sarah Cannon Research Institute, Nashville, Tennessee, and coauthors.
In this study, 36 patients with extranodal (n = 6), nodal (n = 17), or splenic (n = 13) marginal zone lymphoma received pirtobrutinib after extensive prior therapy. All patients had previously received anti-CD20 therapy, 86% had received chemotherapy, and 72% had been treated with a cBTKi. The primary end point was objective response rate (ORR). Key secondary end points included duration of response, progression-free survival (PFS), overall survival (OS), and safety.
The ORR was 55.6%, including 3 complete responses and 17 partial responses. Among patients previously treated with a cBTKi, the ORR was 53.8%. Median duration of response was 17.8 months, and median PFS was 16.6 months. After a median follow-up of 32.4 months, median OS had not been reached.
Dose reductions occurred in 11.1% of patients, and treatment-related adverse events led to permanent treatment discontinuation in 11.1% of patients. The overall safety profile was consistent with previous experience with pirtobrutinib.
These findings support pirtobrutinib as a promising therapeutic option for patients with relapsed or refractory marginal zone lymphoma, particularly in those with prior cBTKi exposure.
Source:
Patel K, Vose JM, Nasta SD, et al. Pirtobrutinib, a highly selective, non-covalent (reversible) BTKi in R/R marginal zone lymphoma: Phase 1/2 BRUIN study. Blood Adv. Published online: January 16, 2026. doi: 10.1182/bloodadvances.2025017489
