Pirtobrutinib Demonstrates Promising Efficacy, Safety Among Patients With B-Cell Malignancies With Richter Transformation

According to an analysis of the Richter transformation subgroup from the phase 1/2 BRUIN study, pirtobrutinib demonstrates encouraging safety and activity among patients with relapsed/refractory (R/R) B-cell malignancies with Richter transformation.

“Pirtobrutinib has shown promising efficacy and tolerability in patients with relapsed or refractory B-cell malignancies, including those who progress on covalent Bruton tyrosine kinase (BTK) inhibitors,” stated lead study author William Wierda, MD, MD Anderson Cancer Center, Houston, Texas, and colleagues.

This research included adult patients (aged ≥ 18 years) with histologically confirmed Richter transformation, an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2, and no limit of previous therapies, with patients receiving first-line treatment added in a protocol amendment. Investigators noted the primary end point of phase 1 of the BRUIN trial, which has been previously reported, was to establish the recommended phase 2 dose for pirtobrutinib monotherapy. The phase 2 primary end point was overall response rate (ORR).

Between December 26, 2019, and July 22, 2022, 82 patients were enrolled; 5 of whom were enrolled during phase 1 and 77 during phase 2. It was noted that all but 1 participant received a starting dose of pirtobrutinib 200 mg once a day as the recommended phase 2 dose. The remaining patient received 150 mg pirtobrutinib once a day, which was not increased to 200 mg. Additionally, 74 (90%) of 82 patients received at least 1 previous Richter transformation-directed therapy, and most patients (61 [74%] of 82) had received previous covalent BTK inhibitor therapy for chronic lymphocytic leukemia (CLL) or Richter transformation.

Analysis results demonstrated an overall response rate of 50% (95% [confidence interval] CI, 38.7 to 61.3). Furthermore, 11 (13%) of 82 patients had a complete response and 30 (37%) of 82 patients had a partial response. Study authors mentioned that 8 patients with ongoing response electively discontinued pirtobrutinib to undergo stem-cell transplantation. Safety data recorded that the most common grade 3 or worse adverse event was neutropenia (n=19), with 0 treatment-related deaths.

“Pirtobrutinib shows promising safety and activity among patients with Richter transformation, most of whom received previous Richter transformation-directed therapy, including covalent BTK inhibitors,” concluded Dr Wierda and colleagues.

“These data suggest that further investigation is warranted of pirtobrutinib as a treatment option for patients with relapsed or refractory Richter transformation after treatment with a covalent BTK inhibitor,” they added.

Source:

Wierda W, Shah N, Cheah C, et al. Pirtobrutinib, a highly selective, non-covalent (reversible) BTK inhibitor in patients with B-cell malignancies: analysis of the Richter transformation subgroup from the multicentre, open-label, phase 1/2 BRUIN study. The Lanc Hem. Published online July 18, 2024. doi: 10.1016/S2352-3026(24)00172-8