Pirtobrutinib shows activity in relapsed and refractory marginal zone lymphoma patients in a Phase 1/2 trialEarly trial shows pirtobrutinib helped some patients with relapsed marginal zone lymphoma

Blood advances Published April 16, 2026 Study authors: Patel Krish, Vose Julie M, Nasta Sunita D, Brown Jennifer R, Maddocks Kami J, Woyach Jennifer A, Sha… PubMed ↗ NCT03740529 ↗ DOI ↗ Editorial oversight: Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

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Key Takeaway

Consider pirtobrutinib for R/R MZL based on early-phase data showing 55.6% ORR and acceptable safety.

This Phase 1/2 clinical trial enrolled 36 patients with relapsed and refractory marginal zone lymphoma. The cohort included 6 patients with extranodal disease, 17 with nodal disease, and 13 with splenic disease. The study assessed pirtobrutinib monotherapy without a concurrent comparator arm. Follow-up duration was 32.4 months (IQR, 28.0-41.3).

The primary outcome was investigator-assessed objective response rate (ORR) by Lugano 2014 criteria. Overall, 20 out of 36 patients achieved an ORR of 55.6% (95% CI, 38.1-72.1). Complete responses were observed in 3 patients (8.3%), while partial responses occurred in 17 patients (47.2%). Among patients with prior cBTKi therapy, the ORR was 53.8% (95% CI, 33.4-73.4).

Secondary outcomes included duration of response, progression-free survival, and overall survival. The median duration of response was 17.8 months (95% CI, 7.4 to nonestimable). Median progression-free survival was 16.6 months (95% CI, 9.0-22.1). Overall survival was nonestimable (95% CI, 29.5-NE). The drug was generally well tolerated. Dose reductions occurred in 4 patients (11.1%), and permanent discontinuation due to treatment-emergent adverse events occurred in 4 patients (11.1%). Serious adverse events were not reported.

Key limitations include the small sample size, the absence of a control group, and the early-phase nature of the trial. Funding and conflicts of interest were not reported. These findings suggest potential efficacy but require validation in larger, randomized settings before changing standard practice.

Researchers evaluated pirtobrutinib in a small group of 36 patients with relapsed or refractory marginal zone lymphoma. The group included patients with extranodal, nodal, and splenic forms of the disease. The study aimed to see how many patients achieved an objective response and to check safety over a follow-up period of about 32 months.

The results showed that 55.6% of patients had an objective response, meaning their tumors shrank significantly. Among those who responded, three patients achieved a complete response, while 17 had a partial response. The average time a response lasted was 17.8 months, and progression-free survival averaged 16.6 months. Overall survival could not be estimated due to the small number of patients.

Safety was generally good, with the drug being well tolerated. However, four patients needed dose reductions and four others stopped treatment due to side effects. Because this is an early-phase trial with a small sample size, these findings should be viewed as preliminary. More research is needed to confirm these benefits and to determine if this treatment should be used widely.

What this means for you:

Early data suggests pirtobrutinib helped some patients with relapsed marginal zone lymphoma, but larger studies are needed.

Study Details

Study typePhase1

Sample sizen = 6

EvidenceLevel 4

Follow-up816.0 mo

PublishedApr 2026

PMID41544219

TrialNCT03740529

View Original Abstract ↓

Marginal zone lymphoma (MZL) is a group of indolent B-cell malignancies with a remitting and relapsing course. For systemic disease, available first-line therapies include anti-CD20 antibody as monotherapy or in combination with chemotherapy (chemoimmunotherapy), with second-line options including covalent Bruton tyrosine kinase inhibitors (cBTKi). However, management of relapsed and refractory (R/R) MZL remains challenging. Pirtobrutinib, a highly selective, noncovalent BTKi has shown promising efficacy and tolerability in poor-prognosis B-cell malignancies following prior therapy, including cBTKi. Here, we report the safety and efficacy of pirtobrutinib in MZL from the phase 1/2 BRUIN study. Endpoints included investigator-assessed objective response rate (ORR) by Lugano 2014 criteria, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Among 36 patients with R/R MZL (extranodal [n = 6]; nodal [n = 17]; splenic [n = 13]), median age was 68 years (range, 22-83) and median prior lines of therapy were 3 (range, 2-10). The ORR was 55.6% (95% confidence interval [CI], 38.1- 72.1), including 3 (8.3%) complete responses and 17 (47.2%) partial responses. Median DOR was 17.8 months (95% CI, 7.4 to nonestimable [NE]), and median PFS was 16.6 months (95% CI, 9.0-22.1). With median follow-up of 32.4 months (IQR, 28.0-41.3), median OS was NE (95% CI, 29.5-NE). The ORR for patients with prior cBTKi therapy was 53.8% (95% CI, 33.4-73.4). Pirtobrutinib was well tolerated with dose reductions in 4 patients (11.1%) and permanent discontinuation due to treatment emergent adverse events in 4 patients (11.1%). Pirtobrutinib showed promising efficacy and safety in patients with heavily pretreated R/R MZL, including prior cBTKi. This trial was registered at www.clinicaltrials.gov as #NCT03740529.

Pirtobrutinib shows activity in relapsed and refractory marginal zone lymphoma patients in a Phase 1/2 trialEarly trial shows pirtobrutinib helped some patients with relapsed marginal zone lymphoma

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