Conference Proceedings
Acquisition of the Recurrent Gly101Val Mutation in BCL2 Confers Resistance to Venetoclax in Patients with Progressive Chronic Lymphocytic Leukemia
Piers Blombery, Mary Ann Anderson, Jianan Gong, Rachel Thijssen, Richard W Birkinshaw, Ella Thompson, Charis E Teh, Tamia Nguyen, Zhen Xu, Christoffer Flensburg, Thomas Lew, Ian Majewski, Daniel Gray, David Alan Westerman, Constantine S Tam, John F Seymour, Peter E Czabotar, David Huang, Andrew W Roberts
BLOOD | AMER SOC HEMATOLOGY | Published : 2018
Abstract
Abstract Venetoclax induces high rates of response (~80%), including complete remissions (CR) in patients with heavily pre-treated chronic lymphocytic leukemia (CLL) through inhibition of BCL2. Despite achieving deep and durable responses, most patients will eventually experience disease progression on treatment. The molecular mechanisms that mediate clinical resistance to venetoclax in vivo are largely unknown. From a cohort of 67 relapsed CLL patients (Anderson et al, Blood 2017; 129:3362-3370) treated with venetoclax on three early phase clinical trials, we performed focussed genomic evaluation in those with CLL-type progressions (as opposed to large cell Ric..
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