The following is a summary of “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,” published in the September 2024 issue of Hematology by Wierda et al.

Researchers conducted a retrospective study to report the safety and activity of pirtobrutinib monotherapy in a subgroup of patients with Richter transformation from the multicentre, open-label, phase 1/2 BRUIN study.

They included adult patients (aged ≥18 years) with histologically confirmed Richter transformation, an Eastern Cooperative Oncology Group performance status score of 0–2, and no limit of previous therapies, with patients receiving first-line treatment added in a protocol amendment (version 9.0, December 15, 2021). Pirtobrutinib 200 mg was administered orally once a day in 28-day cycles. In phase 1 of the BRUIN trial, the primary endpoint was determining the recommended phase 2 dose of pirtobrutinib monotherapy. The phase 2 primary endpoint was the overall response rate. Safety and activity were utilized in all patients who received at least 1 dose of pirtobrutinib.

The results showed that from December 26, 2019, to July 22, 2022, there were 82 patients, 5 in phase 1 and 77 in phase 2. All but 1 received a starting dose of 200 mg of pirtobrutinib daily. The remaining patient received 150 mg of pirtobrutinib daily, which was not escalated to 200 mg. The median age of patients was 67 years (IQR 59–72). 55 (67%) of 82 patients were male and 27 (33%) were female. Most patients were White (65 [79%] of 82)—about 74 (90%) of 82 patients received at least 1 previous Richter transformation-directed therapy. Most patients (61 [74%] of 82) had received previous covalent Bruton tyrosine kinase (BTK) inhibitor therapy for chronic lymphocytic leukemia (CLL) or Richter transformation. The response rate was 50.0%; 11 patients had a complete response, and 30 had a partial response, where 8 patients stopped treatment for stem-cell transplantation. Neutropenia was the most common severe AE, with no treatment-related deaths.

Investigators concluded that Pirtobrutinib showed promising safety and efficacy in treating Richter transformation, even in patients previously treated with covalent BTK inhibitors, suggesting its potential as a valuable treatment option.

Source: thelancet.com/journals/lanhae/article/PIIS2352-3026(24)00172-8/abstract