- A global study co-authored by Providence researchers shows promise for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma.
- A phase 1-2 trial evaluated the efficacy and safety of the oral medication Pirtobrutinib for patients with CLL/SLL.
- The research, published in the New England Journal of Medicine, showed efficacy in patients with heavily pre-treated CLL/SLL, giving hope to those whose options were quite limited after the failure of some existing treatments.
The cancers chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) can be incredibly challenging to treat, especially when existing therapies fail or cause significant side effects. A recent study co-authored by Dr. Krish Patel of the Providence Swedish Cancer Institute and published in the New England Journal of Medicine offers renewed hope for some patients with CLL/SLL. The research highlights the potential of a drug called Pirtobrutinib, particularly for patients who have exhausted several other common treatment options.
Why new CLL and SLL treatment options are needed
Over the past decade, the introduction of medications known as covalent Bruton’s tyrosine kinase (BTK) inhibitors has substantially improved outcomes for patients with CLL/SLL. However, these treatments are not curative, and many patients discontinue them due to progression of their CLL/SLL or side effects. As a result, there is a critical need for additional therapeutic options.
Recognizing this challenge, Dr. Krish Patel collaborated with researchers in 10 countries to conduct a phase 1-2 trial to evaluate the efficacy and safety of Pirtobrutinib, a noncovalent (reversible) Bruton’s tyrosine kinase (BTK) inhibitor, in patients with relapsed or treatment-resistant b-cell cancers such as CLL and SLL.
Phase 1-2 trial shows promising results
The phase 1-2 trial (the BRUIN trial) involved 317 patients diagnosed with CLL or SLL, including 247 who had previously received a covalent BTK inhibitor. Patients were enrolled from sites in 10 countries between March 2019 and July 2022. The primary objective was to assess the overall response (partial response or better) using independent review, with secondary endpoints focusing on progression-free survival and safety.
The researchers reported compelling efficacy results among patients who had previously received a covalent BTK inhibitor, thereby offering renewed hope to those with limited treatment options. Throughout the trial, the most commonly observed adverse events included infections, bleeding, and neutropenia, which is an abnormally low count of a type of white blood cell.
“Patients with CLL/SLL who experience progression of their disease on covalent BTK inhibitors, unfortunately, may have limited options for further therapy," explains Dr. Patel. "Targeting BTK has proven a crucial strategy in the treatment of CLL/SLL, and in the BRUIN trial, we demonstrate that we can continue to effectively target BTK with Pirtobrutinib, a non-covalent BTK inhibitor, even when existing BTK inhibitors are no longer effective. Pirtobrutinib will potentially offer many patients with CLL/SLL the potential for further improved outcomes."
This research sheds light on the potential of Pirtobrutinib as a viable treatment option for patients with CLL and SLL who have exhausted previous therapies. The findings highlight the importance of ongoing research and collaboration within the scientific community to identify new approaches to combat aggressive forms of leukemia and were highlighted in a NEJM editorial outlining the science behind this study.
While further studies and clinical trials are needed to solidify these findings, these discoveries offer renewed optimism to those affected by this challenging disease and its manifestations.