ASH 2025 Pirtobrutinib shows superior effect in untreated CLL/SLL

MedNet.nl: Pirtobrutinib significantly improves progression-free survival (PFS) in previously untreated patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) compared with standard chemoimmunotherapy. This is evident from the initial results of the phase 3 BRUIN CLL-313 study, which were announced in a late-breaking abstract.

Pirtobrutinib is a selective, non-covalent Bruton tyrosine kinase inhibitor (BTKI) that has previously shown promising results in patients with relapsed/refractory CLL/SLL. BRUIN CLL-313 is the first randomized phase 3 trial to directly compare pirtobrutinib with standard treatment in previously untreated patients, including older patients who may only be able to receive one line of therapy.

In this global trial, 282 patients with untreated CLL/SLL without del(17p) were randomized 1:1 to pirtobrutinib monotherapy (200 mg once daily) or six cycles of bendamustine plus rituximab (BR). Crossover to pirtobrutinib was allowed upon progression in the BR group.

After a median follow-up of 28.1 months, pirtobrutinib demonstrated significantly improved PFS compared with BR (HR=0.199; p<0.0001). The median duration of treatment was 32.3 months for pirtobrutinib versus 5.6 months for BR. The PFS rate at 24 months was 93.4% for pirtobrutinib versus 70.7% for BR. The benefit was consistently observed in all prespecified subgroups, including patients with mutated IGHV (HR=0.293) and unmutated IGHV (HR=0.172). Overall survival favored pirtobrutinib (HR=0.257; p=0.0261), despite a crossover rate of 52.9% of BR patients after progression.

Pirtobrutinib was well tolerated, with a lower rate of serious adverse events (grade ≥3) than BR (40.0 vs 67.4%). Discontinuation of treatment due to adverse events was rare (4.3 vs 15.2%). Atrial fibrillation or atrial flutter occurred in 1.4% of the pirtobrutinib arm (only one of whom was older than 75 years). No treatment-related deaths were reported.

Jurczak W, Kwiatek M, Czyz J, et al. Pirtobrutinib vs bendamustine plus rituximab (BR) in patients with CLL/SLL: First results from a randomized phase III study Examining a non-covalent BTK inhibitor in untreated patients. ASH Annual Meeting & Exhibition, abstract LBA-3.

This article was originally published in Dutch on MedNet.nl