Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML

DiNardo, Courtney D.; Tiong, Ing Soo; Quaglieri, Anna; MacRaild, Sarah; Loghavi, Sanam; Brown, Fiona C.; Thijssen, Rachel; Pomilio, Giovanna; Ivey, Adam; Salmon, Jessica M.; Glytsou, Christina; Fleming, Shaun; Zhang, Q.; Ma, Huaxian; Patel, Keyur P.; Kornblau, Steven M.; Xu, Zhen; Chua, Chong Chyn; Chen, Xufeng; Blombery, Piers; Flensburg, Christoffer; Cummings, Nik; Aifantis, Iannis; Kantarjian, Hagop M.; Huang, David C.S.; Roberts, Andrew W.; Majewski, Ian J.; Konopleva, Marina; Wei, Andrew H.

doi:10.1182/blood.2019003988

articleBloodJan 14, 2020BRONZE OA

Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML

CDCourtney D. DiNardo ISIng Soo Tiong AQAnna Quaglieri SMSarah MacRaild SLSanam Loghavi

The University of Texas MD Anderson Cancer Center · The Alfred Hospital · +8 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

The BCL-2 inhibitor venetoclax combined with hypomethylating agents or low-dose cytarabine represents an important new therapy for older or unfit patients with acute myeloid leukemia (AML). We analyzed 81 patients receiving these venetoclax-based combinations to identify molecular correlates of durable remission, response followed by relapse (adaptive resistance), or refractory disease (primary resistance). High response rates and durable remissions were typically associated with NPM1 or IDH2 mutations, with prolonged molecular remissions prevalent for NPM1 mutations. Primary and adaptive resistance to venetoclax-based combinations was most commonly characterized by acquisition or enrichment of clones…

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Topics & keywords

Topics

Keywords

Venetoclax
NPM1
Cytarabine
Oncology
Azacitidine
Myeloid leukemia
Medicine
Alemtuzumab

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