Developing novel therapeutic approaches for classical and variant hairy cell leukemia
Omar Abdel-Wahab
MDMemorial Sloan Kettering Cancer Center
Project Term: October 1, 2021 - September 30, 2025
In this proposal, we have combined clinical and research expertise in HCL across Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, the University of Pennsylvania, and Yale University to develop newer targeted therapeutics for every stage and subtype of hairy cell leukemia. Capitalizing on this combined expertise, our proposal stands to significantly advance treatment strategies for hairy cell leukemia through the following aims: to test BRAF inhibition for initial treatment of classical hairy cell leukemia, test new oral inhibitors of the MAP kinase signaling pathway known as ERK inhibitors in both classical and variant hairy cell leukemia, evaluate totally new treatments that degrade BRAF, and develop T-cell immunotherapies for the first time in hairy cell leukemia.
Hairy cell leukemia (HCL) is a blood cancer driven by activation of the MAP kinase signaling pathway. Although chemotherapy results in high initial response rates, HCL is incurable and 40% of patients require repeated courses of chemotherapy which leads to immunosuppression and risk of additional cancers. To this end, it was recently discovered that nearly 100% of patients with classical HCL (HCLc) have a BRAF gene mutation and respond to the oral BRAF inhibitor drug vemurafenib. Despite these advances, some HCL patients develop resistance to vemurafenib and the success rate using vemurafenib for the initial treatment of HCL is unknown. In addition, a rarer form of HCL known as variant HCL (HCLv) lacks the BRAF mutation and HCLv patients are therefore not eligible to receive BRAF inhibitor therapy.
In this proposal, we combine the clinical and research expertise in HCL across Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, the University of Pennsylvania, and Yale University to develop new targeted therapeutics for every stage and subtype of HCL. Capitalizing on this combined expertise, our proposal stands to significantly advance treatment for HCL through the following aims: to test BRAF inhibition for initial treatment of HCLc, test new oral inhibitors of the MAP kinase signaling pathway known as ERK inhibitors in HCLc and HCLv, evaluate totally new treatments that degrade BRAF, and develop T-cell immunotherapies for the first time in HCL.
The Hairy Cell Leukemia Foundation (HCLF) and The Leukemia & Lymphoma Society (LLS) have joined forces to create the HCL2025 program to support targeted research to build a more comprehensive foundational understanding of the molecular basis of hairy cell leukemia (HCL), develop additional therapies, and optimize outcomes for patients with this disease.