Towards precision medicine for AML

Hartmut Döhner*, Andrew H. Wei, Bob Löwenberg

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

176 Citations (Scopus)

Abstract

With rapid advances in sequencing technologies, tremendous progress has been made in understanding the molecular pathogenesis of acute myeloid leukaemia (AML), thus revealing enormous genetic and clonal heterogeneity, and paving the way for precision medicine approaches. The successful development of precision medicine for patients with AML has been exemplified by the introduction of targeted FLT3, IDH1/IDH2 and BCL-2 inhibitors. When used as single agents, these inhibitors display moderate antileukaemic activity. However, augmented clinical activity has been demonstrated when they are administered in combination with drugs with broader mechanisms of action targeting epigenetic and/or other oncogenic signalling pathways or with conventional cytotoxic agents. The development of immunotherapies has been hampered by the expression of antigens that are expressed by both leukaemic and non-malignant haematopoietic progenitor cells; nonetheless, a diverse range of immunotherapies are now entering clinical development. This myriad of emerging agents also creates challenges, such as how to safely combine agents with different mechanisms of action, the need to circumvent primary and secondary resistance, and new challenges in future clinical trial design. In this Review, we discuss the current state of precision medicine for AML, including both the potential to improve patient outcomes and the related challenges.

Original languageEnglish
Pages (from-to)577-590
Number of pages14
JournalNature Reviews Clinical Oncology
Volume18
Issue number9
DOIs
Publication statusPublished - Sept 2021

Bibliographical note

Funding Information:
H.D. has acted as an advisor for AbbVie, Agios, Amgen, Astellas, Astex Pharmaceuticals, AstraZeneca, Bristol Myers Squibb, Celgene, GEMoaB, Helsinn, Janssen, Jazz Pharmaceuticals, Novartis, Oxford Biomedica and Roche, and has received research funding from Agios, Amgen, Astellas, Bristol Myers Squibb, Celgene, Jazz Pharmaceuticals, Novartis and Pfizer. A.W. has acted as an advisor for AbbVie, Agios, Amgen, Bristol Myers Squibb, Gilead, Janssen, Macrogenics, Novartis, Pfizer, Roche and Servier, has received research funding from AbbVie, Amgen, Astra Zeneca, Bristol Myers Squibb, Novartis and Servier, serves on speakers bureaus for AbbVie, Celgene and Novartis, and receives royalty payments from the Walter and Eliza Hall Institute of Medical Research related to venetoclax. B.L. has acted as an advisor for AbbVie, AIMM Therapeutics, Astellas, Catamaran Bio Inc., Bristol Myers Squibb, Celgene, Clear Creek Bio, F. Hoffmann La Roche, GEMoaB, Kronos Bio Inc and Oxford Biomedica, and holds shares in Frame Pharmaceuticals.

Funding Information:
The work of H.D is supported in part by the Deutsche Forschungsgemeinschaft (DFG; Collaborative Research Center 1074), DFG grant DO 436/7-1, and a grant by the Bundesministerium für Bildung und Forschung (BMBF; DRAMA 01KT1603).

Publisher Copyright:
© 2021, Springer Nature Limited.

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