Pirtobrutinib, a Highly Selective, Non-covalent (Reversible) BTKi in R/R Marginal Zone Lymphoma: Phase 1/2 BRUIN Study.

Patel, K.; Vose, JM.; Nasta, SD.; Brown, JR.; Maddocks, KJ.; Woyach, JA.; Shah, NN.; Fakhri, B.; Tessoulin, B.; Ma, S.; Jagadeesh, D.; Lech-Maranda, E.; Coombs, CC.; Patel, MR.; Rhodes, JM.; Ujjani, CS.; Hoffmann, MS.; Cheah, CY.; Munir, T.; Lewis, DJ.; Scarfo, L.; Eyre, TA.; Alencar, AJ.; Cohen, JB.; Zelenetz, AD.; Tsai, DE.; Li, M.; Bian, Y.; Abada, PB.; Balbas, M.; Zinzani, PLL.

Pirtobrutinib, a Highly Selective, Non-covalent (Reversible) BTKi in R/R Marginal Zone Lymphoma: Phase 1/2 BRUIN Study.

All Authors

Patel, K.

Vose, JM.

Nasta, SD.

Brown, JR.

Maddocks, KJ.

Woyach, JA.

Shah, NN.

Fakhri, B.

Tessoulin, B.

Ma, S.

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LTHT Author

Munir, Talha

LTHT Department

Oncology
Haematology

Publication Date

2026

Item Type

Journal Article

Abstract

Marginal zone lymphoma (MZL) is a group of indolent B-cell malignancies that have a natural history that follows a remitting and relapsing course. 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 covalent (c) Bruton tyrosine kinase inhibitors (BTKi). However, management of relapsed and refractory (R/R) MZL remains a challenge. Pirtobrutinib, a highly selective, non-covalent BTKi has shown promising efficacy and tolerability in patients with poor-prognosis B-cell malignancies following prior therapy, including cBTKi. Here we report the safety and efficacy of pirtobrutinib in patients with MZL from the phase 1/2 BRUIN study. Endpoints included investigator assessed ORR by Lugano 2014 criteria, DOR, PFS, OS, and safety. Among 36 R/R MZL patients (EMZL: n=6; NMZL: n=17; SMZL: n=13), median age was 68 years (range, 22-83) and median prior lines of therapy were 3 (range, 2-10) including anti-CD-20 antibody (100%), chemotherapy (86%) and cBTKi therapy (72%). 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-non-estimable [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 TEAEs in 4 (11.1%). Pirtobrutinib showed promising efficacy and safety in patients with heavily pre-treated R/R MZL, including prior cBTKi. NCT03740529. Copyright © 2026 American Society of Hematology.