The Bottom Line:
The latest results from the BRUIN study show that when patients with Richter’s transformation were treated with pirtobrutinib, about half of the patients responded to treatment. Additionally, pirtobrutinib was well-tolerated with low discontinuation rates due to drug-related toxicity.
Who Performed the Research and Where Was it Presented:
Dr. Nirav Shah from Medical College of Wisconsin and colleagues presented the results at the American Society for Hematology Annual Meeting in 2022.
Background:
Richter’s transformation (a.k.a. Richter’s syndrome) is a rare complication of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), where the cancer cells transform into a much more aggressive lymphoma. It currently has no approved therapies and is associated with an extremely poor prognosis.
In this interview, our own Dr. Brian Koffman interviewed Dr. Nirav Shah, Associate Professor of Medicine at Medical College of Wisconsin, focusing on hematological malignancies. They discussed the latest results from a clinical trial of pirtobrutinib, a new reversible Bruton tyrosine kinase (BTK) inhibitor, for treating Richter’s transformation.
Methods and Participants:
The BRUIN study is a phase 1/2 clinical trial testing pirtobrutinib in patients with previously treated B-cell malignancies, including those with CLL and Richter’s transformation. While the study initially only enrolled patients with previously treated Richter’s transformation, it was later amended to include patients with untreated Richter’s transformation. Thus far, over 80 patients with Richter’s transformation have been treated in this study, which is huge because Richter’s transformation is relatively rare.
Results:
- Pirtobrutinib is a highly selective, non-covalent (reversible) BTK inhibitor, which inhibits both wildtype and C481-mutant BTK.
- Safety was evaluated in the BRUIN study of over 700 patients, and there were very few serious side effects (grade 3 or higher).
- The most common adverse events were fatigue (26%), diarrhea (22%), low white blood cell counts (20%), and bruising (19%).
- The side effects of pirtobrutinib were different from previous covalent BTK inhibitors such as ibrutinib and acalabrutinib, and there were very low rates of atrial fibrillation (1%) and bleeding (2%).
- Only 2% of patients discontinued treatment due to an adverse event.
- In patients with Richter’s transformation, the overall response rate was 52%, and a small subset of patients achieved complete remission.
- For some patients, pirtobrutinib provided a bridge to pursue curative-intent therapy such as allogeneic stem cell transplant.
- The median survival time after starting treatment was 13 months.
Conclusions:
In this study, when patients with Richter’s transformation were treated with pirtobrutinib, about half of the patients responded to treatment. This is a promising result in a very hard-to-treat group of patients. While pirtobrutinib is probably not a curative, it may help stabilize the disease, improve quality of life, and potentially serve as a bridge to other therapies. Additionally, pirtobrutinib was well-tolerated with low discontinuation rates due to drug-related toxicity.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Efficacy of Pirtobrutinib, a Highly Selective, Non-Covalent (Reversible) BTK Inhibitor in Richter Transformation: Results from the Phase 1/2 BRUIN Study
Take care of yourself first.
Ann Liu, PhD
