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Acute myeloid leukemia

Two decades of targeted therapies in acute myeloid leukemia

Leukemia volume 35, pages 651–660 (2021)Cite this article

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Abstract

Precision medicine is gaining importance in the treatment of acute myeloid leukemia (AML). Objectively reviewing past and current knowledge aids guiding future research. Therefore, we provide a complete overview of all phase II and phase III trials investigating targeted therapies in AML and their primary endpoints over the past two decades in perspective of their clinical benefit. We assessed whether drugs were primarily designed to treat AML or were repurposed and how successful they were based on progression of distinct drugs from phase II to phase III to FDA-approval. Between January 2000 and September 2020, 167 agents with 96 targets were investigated in 397 phase II trials. Twenty-eight agents were steered towards phase III, after three phase II trials on average. Repurposed drugs less often advanced in clinical development than drugs primarily developed for AML. Composite responses were the most prevalent primary endpoints in phase II. Of the eight FDA-approved drugs, none investigated quality of life at time of approval, and three out of eight have yet to show benefit in overall survival. Returns on targeted therapy research remain lean for AML patients. Future trials should not overlook non-targeted agents and foremost study endpoints proven to predict patient well-being.

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Fig. 1: Search strategy.
Fig. 2: Targets and targeted agents in phase II and II clinical trials.
Fig. 3: Primary outcomes in phase II and III clinical trials.

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Acknowledgements

The authors thank Noor Gieles for extensive proof reading.

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Author notes

  1. These authors contributed equally: David G. J. Cucchi, Tobias B. Polak

Authors and Affiliations

  1. Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands

    David G. J. Cucchi, Gert J. Ossenkoppele, Jacqueline Cloos, Sonja Zweegman & Jeroen J. W. M. Janssen

  2. Erasmus School of Health Policy and Management, Erasmus University Rotterdam, Rotterdam, The Netherlands

    Tobias B. Polak & Carin A. Uyl–De Groot

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Cucchi, D.G.J., Polak, T.B., Ossenkoppele, G.J. et al. Two decades of targeted therapies in acute myeloid leukemia. Leukemia 35, 651–660 (2021). https://doi.org/10.1038/s41375-021-01164-x

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