Journal article

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

CD DiNardo, IS Tiong, A Quaglieri, S MacRaild, S Loghavi, FC Brown, R Thijssen, G Pomilio, A Ivey, JM Salmon, C Glytsou, SA Fleming, Q Zhang, H Ma, KP Patel, SM Kornblau, Z Xu, CC Chua, Xufeng Chen, P Blombery Show all

Blood | AMER SOC HEMATOLOGY | Published : 2020

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..

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Grants

Awarded by National Health and Medical Research Council of Australia


Awarded by Independent Research Institutes (Infrastructure Support Scheme grant)


Awarded by Cancer Council Victoria


Awarded by Medical Research Future Fund


Awarded by National Cancer Institute, National Institutes of Health cancer center support grant


Funding Acknowledgements

This work was supported in part by grants from the National Health and Medical Research Council of Australia (1162809, 126843, 1113133, and 1113577), Leukemia and Lymphoma Society Specialized Centre of Research (SCOR-CI Strasser), Independent Research Institutes (Infrastructure Support Scheme grant 9000220), the Cancer Council Victoria (grant-in-aid 1124178) (I.J.M.), a Victorian State Government Operational Infrastructure Support grant, and fellowship support from the Victorian Cancer Agency (I.J.M.), the National Health and Medical Research Council of Australia (D.C.S.H., A.W.R.), the Leukemia Lymphoma Society (R.T.), the Felton Bequest (I.J.M.), the andMedical Research Future Fund (1141460) (A.H.W.). Scholarship support was provided by a Melbourne University Research Scholarship (A.Q.). This research is additionally supported in part by National Cancer Institute, National Institutes of Health cancer center support grant P30 CA016672 and the V Foundation Lloyd Family Clinical Scholar Award (C.D.D.).