The Bottom Line:
Pirtobrutinib continues to demonstrate promising and durable efficacy in heavily pre-treated patients with relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), who have been previously treated with a covalent Bruton tyrosine kinase (BTK) inhibitor. Pirtobrutinib may be an important option to extend the benefit of BTK inhibition among patients who progressed on previous BTK inhibitors.
Who Performed the Research and Where Was it Presented:
Dr. Jennifer Woyach from the Ohio State University and colleagues presented the results at the American Society for Hematology Annual Meeting in 2022.
Background:
Pirtobrutunib is a reversible (non-covalent) BTK inhibitor. This means that it binds specifically to BTK, but it binds reversibly, in a different way than irreversible (covalent) BTK inhibitors such as ibrutinib, acalabrutinib, and zanubrutinib. Because it does in the same way to BTK as the three approved BTK inhibitors, when BTK mutations occur where those three bind, pirtobrutinib remains able to turn off BTK when the irreversible binders are no longer effective.
In this interview, Dr. Brian Hill, Director of the Lymphoid Malignancies Program and a Staff Physician at the Cleveland Clinic Taussig Cancer Institute, interviewed Dr. Jennifer Woyach, co-director of the Leukemia Research Program at the James Cancer Center of the Ohio State University in Columbus, OH. They discussed updated results from the BRUIN study that specifically looked at pirtobrutinib’s efficacy in patients with CLL / SLL who had previously been treated with a covalent BTK inhibitor.
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 / SLL. This analysis specifically looked at patients with CLL / SLL who had previously been treated with a covalent BTK inhibitor.
Results:
- In total, 276 pts with CLL / SLL had received a prior BTK inhibitor, and the median number of prior therapies was three.
- Most patients (75%) discontinued prior BTK inhibitor therapy due to disease progression.
- These patients were heavily pre-treated: 89% had been treated with an anti-CD20 antibody, 80% had been treated with chemotherapy, 44% had been treated with a BCL2 inhibitor, 24% had been treated with a PI3K inhibitor, 6% had received CAR-T cell therapy.
- The median progression-free survival was 19.4 months, and the estimated progression-free survival rates were 68% at 12 months and 54% at 18 months.
- Pirtobrutinib was very well-tolerated, and only 2% of patients discontinued due to a treatment-related adverse event.
Conclusions:
Pirtobrutinib continues to demonstrate promising and durable efficacy in heavily pre-treated patients with relapsed/refractory CLL / SLL previously treated with a covalent BTK inhibitor. Pirtobrutinib may be an important option to extend the benefit of BTK inhibition among patients who progressed on previous BTK inhibitors.
Now that it has been approved in mantle cell lymphoma, there is reason to expect it will be available “off-label” for CLL / SLL.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Efficacy of Pirtobrutinib in Covalent BTK-Inhibitor Pre-Treated Relapsed / Refractory CLL / SLL: Additional Patients and Extended Follow-up from the Phase 1/2 BRUIN Study
Take care of yourself first.
Ann Liu, PhD
