SOHO 2019: Novel Reversible BTK Inhibitor Therapy for Chronic Lymphocytic Leukemia
Posted: Wednesday, September 25, 2019
According to research presented at the 2019 Society of Hematologic Oncology (SOHO) Annual Meeting (Abstract EXABS-CLL-422), reversible Bruton’s tyrosine kinase (BTK) inhibitors are a promising potential therapy for patients with chronic lymphocytic leukemia (CLL). “Reversible inhibitors of BTK represent an exciting therapeutic strategy in [chronic lymphocytic leukemia] and other B-cell malignancies,” concluded Jennifer A. Woyach, MD, of The Ohio State University Comprehensive Cancer Center.
Unlike conventional, irreversible BTK inhibitors, reversible BTK inhibitors do not require interaction with the amino acid C481 due to noncovalent binding. Therefore, their efficacy is not compromised by C481 mutations, making them a potential therapeutic alternative for patients who previously underwent treatment with irreversible BTK inhibitors before experiencing a relapse. Examples of this type of therapy include GDC-0853, a highly selective inhibitor that was successful in preclinical models; ARQ-531, a multitargeted inhibitor that was shown to be effective in samples from patients who were resistant to ibrutinib and that outperformed ibrutinib in mouse models; and vecabrutinib, which inhibits both BTK and interleukin-2–inducible T-cell kinase (ITK).
Of these investigational agents, GDC-0853 is thus far the only one to have accumulated data regarding treatment outcomes, although they are not definitive, Dr. Woyach noted. In that trial, 7 of 14 patients with CLL achieved a complete response, and progression-free survival was 2.5 months. In studies for all of the other reversible BTK inhibitors mentioned previously, the toxicity profile was favorable, and phase I dose escalation was recommended. Optimal therapy implementation has not yet been identified due to the actively growing nature of this area of research.
Disclosure: The study authors’ disclosure information can be found at soho2019.com.
