Conference Proceedings

High Clonal Complexity of Resistance Mechanisms Occurring at Progression after Single-Agent Targeted Therapy Strategies in Chronic Lymphocytic Leukemia

Ella R Thompson, Tamia Nguyen, Yamuna Kankanige, Mary Ann Anderson, Sasanka M Handunnetti, Rachel Thijssen, Paul Sung-Hao Yeh, Constantine S Tam, John F Seymour, Andrew W Roberts, David Alan Westerman, Piers Blombery

BLOOD | AMER SOC HEMATOLOGY | Published : 2020

Abstract

Progression of chronic lymphocytic leukemia (CLL) on venetoclax (VEN) and BTK inhibitors (BTKi) is associated with acquired genomic variants in BCL2/MCL1/BCL2L1 and BTK/PLCG2, respectively, in some patients. We aimed to assess the clonal structure and evolution of resistance in patients (pts) with progressive disease treated with single agent VEN or BTKi (or both as sequential monotherapies) using next generation sequencing (NGS) and single cell sequencing. Seven pts with CLL and 1 with mantle cell lymphoma (MCL) with disease progression on VEN, ibrutinib (IBR) or zanubrutinib (ZANU) were identified from patients treated at our institutions. Pts were selected on the basis of m..

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