Pirtobrutinib resulted in an 82.5% objective response rate in patients with Waldenström macroglobulinemia, and the ORR was 81.0% in those who previously received a Bruton’s tyrosine kinase inhibitor. The results were published by M. Lia Palomba, MD, of Memorial Sloan Kettering, and colleagues in The Lancet Haematology.
The researchers used data from the open-label, multicenter, phase I/II BRUIN study, which included patients with relapsed or refractory B-cell malignancies from 29 sites in eight countries. Adult patients with confirmed WM were included. In phase I, they were randomized to receive oral pirtobrutinib at 100 to 300 mg daily in 28-day cycles. The recommended phase 2 dose (RP2D) was determined to be 200 mg daily.
Between August 12, 2019, and March 14, 2022, 778 patients received pirtobrutinib, including 80 with relapsed or refractory WM (median age, 68.5 years; 65% were male). Patients had received a median of three prior lines of therapy, and 79% had previously received a BTK inhibitor. In the WM cohort, 73 patients (91%) received the RP2D.
Responses to treatment included one complete response, eight very good partial responses, 49 partial responses, and eight minor responses. The ORR was 88.2% for patients who were BTK inhibitor-naïve.
Grade 3 or higher treatment-emergent adverse events were reported in 57 patients (71%), most commonly neutropenia or neutrophil count decrease (19%) and anemia (24%). Five deaths were reportedly treatment-related; four patients required treatment-related dose reductions, and 12 patients discontinued pirtobrutinib.
The researchers concluded that pirtobrutinib “might be a promising new therapeutic option for patients with relapsed or refractory WM, particularly in those previously exposed to covalent BTK inhibitors, for whom durable and effective treatments are needed.”
The study was funded by Eli Lilly and Company.
Reference
Palomba ML, Patel MR, Eyre TA, et al. Safety and activity of pirtobrutinib in patients with relapsed or refractory Waldenström macroglobulinaemia: 5-year follow-up of the open-label, multicentre, phase 1/2 BRUIN trial. Lancet Haematol. 2026;13(5):e284-e296. doi:10.1016/S2352-3026(26)00037-2
