Identification of Structurally Novel BTK Mutations That Drive Resistance to BTK Inhibitors in CLL and Non-Hodgkin Lymphomas

SUMMARY

• Non-Hodgkin’s lymphoma is among the most common types of cancer in the US consisting of a diverse group of lymphocytic malignancies. Most of these malignancies are B-cell of which chronic lymphocytic leukemia (CLL) is one of them.
• CLL is a demanding disease for patients and early treatment methods have not been effective. Treatment is only prescribed after the disease has progressed and bothersome symptoms appear.
• Ibrutinib (ibr) is a Bruton tyrosine kinase (BTK) inhibitor that has demonstrated high response rates in relapsed/refractory CLL. However, many patients continue the progression of leukemia or Richter transformations even with ibr treatment.
• The faculty inventor has identified structurally novel BTK mutations that drive resistance to BTK inhibitors in CLL and other non-Hodgkin lymphomas. These BTK mutations are crucial biomarkers leading to patient management decisions.
• This invention lends further insight into the diverse mechanisms of ibr resistance and has important implications for the development of next-generation early detection treatments for CLL.

ADVANTAGES

ADVANTAGES

• Early detection of low-abundance resistance mutation
• Insight into the diversity of ibr resistance

APPLICATIONS

• BTK mutations as biomarkers for mutation detection in relapsed patients, and for patient management decisions
• Prevention and treatment of ibrutinib resistance in patients with CLL and other types of non-Hodgkin lymphoma (NHL)
• Development of next-generation BTK inhibitors

PUBLICATIONS

• ­Sharma S, Galanina N, Guo A, Lee J, Kadri S, Van Slambrouck C, Long B, Wang W, Ming M, Furtado LV, Segal JP, Stock W, Venkataraman G, Tang WJ, Lu P, Wang YL. Identification of a structurally novel BTK mutation that drives ibrutinib resistance in CLL. Oncotarget. 2016 Oct 18;7(42):68833-68841. doi: 10.18632/oncotarget.11932. PMID: 27626698; PMCID: PMC5356593.

• US11118233B2