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

Relapsed/refractory (R/R) follicular lymphoma (FL) is a chronic disease often requiring multiple lines of therapy. Covalent (c) Bruton tyrosine kinase inhibitor (BTKi) monotherapy has resulted in variable response rates, yet patients invariably experience relapse. While newer therapies such as bispecific antibodies and CAR T cell therapy are available, patient access and eligibility remain challenging. Here, we report the safety and efficacy of pirtobrutinib, a non-covalent (reversible) BTKi, monotherapy in a R/R FL patient cohort from the multicenter phase 1/2 BRUIN study. Key endpoints included investigator-assessed ORR per Lugano 2014 criteria, DoR, PFS, OS, and safety. Among 48 patients with FL, the median age was 64.5 years (range, 37.0-85.0). Patients had received a median of 3 (range, 1-12) prior lines of therapy. The ORR with pirtobrutinib was 50.0% (95% CI, 35.2-64.8), and median DOR was 5.5 months (95% CI, 3.7- NE). Median PFS was 5.8 months (95% CI, 3.8-8.1), and median OS was NE, with a median follow-up of 20.4 months (IQR, 13.7, 27.5). The estimated DOR, PFS, and OS rates at 18 months were 41.0% (95% CI, 20.1-60.9), 32.3% (95% CI, 19.1-46.2), and 78.3% (95% CI, 62.1-88.1), respectively. Pirtobrutinib was well-tolerated with two patients (4.2%) discontinuing treatment due to AEs (one treatment-related) and four patients (8.3%) having dose reductions due to AEs (all treatment-related). Pirtobrutinib showed promising efficacy and was well tolerated in this cohort of heavily pre-treated patients with R/R FL warranting further investigation.