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. These therapies 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.
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 allogeneic stem cell transplantation.