Researchers continue to refine and improve targeted drug therapies that have changed the most common form of adult leukemia – from an incurable to a chronic condition. New data published in the New England Journal of Medicine offers another treatment option for patients who have stopped responding to the first and second-generation drugs.

Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia. While chemoimmunotherapy remains an important option for a subset of patients with CLL, over the past decade, the global standard of care has gradually moved towards targeted therapies such as covalent (c) Bruton tyrosine kinase inhibitor (BTKi) and the BCL2 inhibitor which block the protein essential for CLL-cell survival and spread throughout the body.

Over the course of treatment, some patients with CLL, and also small lymphocytic lymphoma (SLL), will develop resistance to BTKi treatment, resulting in poor outcomes. Therefore, new therapeutic options are needed for these patients.

In the study co-led by The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James), researchers examined whether Pirtobrutinib, a highly selective and reversible BTKi, would re-establish BTK inhibition in patients with CLL and SLL who have become resistant to the first and second generation covalent inhibitors—ibrutinib, and acalabrutinib and zanubrutinib.

In this study of 247 patients with CLL and SLL, researchers showed that pirtobrutinib was safe and effective in a population of patients who had received intensive prior treatments with other BTK inhibitors. Results also showed progression-free survival with the 12-month and 18-month overall survival rates among all BTKi pretreated patients at 86 percent and 81 percent, respectively.

“Pirtobrutinib is currently approved for mantle cell lymphoma, but it represents a new potential therapy option for patients who have become resistant to BTKi and/or BCL2 inhibitors where there are few, if any, standard therapy options,” said the study’s co-first author Jennifer Woyach, MD, a hematologist with the OSUCCC – James and co-leader of the OSUCCC – James Leukemia Research Program and D. Warren Brown ,Professor of Leukemia Research.

“Our study also shows that continued targeting of BTK, even after therapeutic strategies using the first- and second-generation covalent inhibitors, is effective,” said Woyach, also a professor of hematology in the Ohio State College of Medicine. “Many patients with CLL and SLL will be treated chronically with BTKi, and the long-term safety of pirtobrutinib still remains to be defined.”

Study participants were ages 36 to 88, and the number of prior therapies the patients received ranged from one to 11. In addition to prior BTKi therapy, patients had also received prior anti-CD20 antibody, chemotherapy, BCL2 inhibitor, PI3K inhibitor, CAR-T-cell therapy and allogenic stem cell transplantation.

Financial support for this study comes from Loxo@Lilly, the oncology unit of Eli Lilly and Company.

To learn more about CLL research and patient cancer care at the OSUCCC – James, visit cancer.osu.edu/cll.

(SRU/NEWSWISE)