BRUIN phase I/II results: Pirtobrutinib in R/R MZL

The phase I/II BRUIN study (NCT03740529) evaluated pirtobrutinib, a highly selective, non-covalent (reversible) Bruton tyrosine kinase inhibitor (BTKi), in patients with relapsed/refractory (R/R) B-cell malignancies. Results from the relapsed/refractory (R/R) marginal zone lymphoma (MZL) cohort (N = 36) were published in Blood Advances by Patel et al. Endpoints included investigator-assessed overall response rate (ORR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety.

Key data: The ORR was 55.6% (95% confidence interval [CI], 38.1–72.1), including complete responses and partial responses in 8.3% and 47.2% of patients, respectively. With a median follow-up time of 25.8 months, the median DoR was 17.8 months (95% CI, 7.4–non-estimable [NE]). Median PFS was 16.6 months (95% CI, 9.0–22.1), with a median follow-up of 27.7 months. The 24-month OS rate was 77.0% (95% CI, 59.3–87.8). Treatment-emergent adverse events (TEAEs) were reported by 97.2% of patients. The most common Grade ≥3 TEAEs were neutropenia / decreased neutrophil count (33.3%), anemia (16.7%), infections (13.9%), and decreased platelet count (11.1%).

Key learning: Pirtobrutinib demonstrated efficacy and a manageable safety profile in heavily pretreated patients with R/R MZL, representing a potential therapeutic option in this difficult-to-treat population.