Program DHC-Virtual
20 - 21 January 2021
Clinical Abstracts session 4
Two decades of targeted therapies in acute myeloid leukemia
21 January
11:54 12:06
D.G.J. Cucchi

Two decades of targeted therapies in acute myeloid leukemia

David Cucchi (1), Tobias Polak (2), Gert Ossenkoppele (1), Carin Uyl - De Groot (2), Jacqueline Cloos (1), Sonja Zweegman (1), Jeroen Janssen (1)
(1) Cancer Center Amsterdam, Amsterdam UMC, Location VUmc, Hematology, Amsterdam, (2) Erasmus University Rotterdam, Erasmus School of Health Policy & Management, Rotterdam
No potential conflicts of interest

Precision medicine is gaining importance in the treatment of acute myeloid leukemia (AML). A comprehensive overview of all trials, targets and targeted drugs investigated over the past two decades in perspective of their clinical effects is lacking. Here, we provide an overview of all targeted therapies investigated in the past two decades in phase II and III trials, their primary endpoints and the resulting clinical benefit in AML. 


We systematically identified all phase II and phase III trials investigating targeted therapies in AML using and MEDLINE between January 2000 and September 2020. Clinical benefit was assessed using ESMO-Magnitude of Clinical Benefit Scale v1.1. We used the manufacturer’s data and trial information to assess whether drugs were primarily designed to treat AML or were repurposed. Success rates were assessed based on progression of distinct drugs from phase II to phase III to FDA-approval. Primary endpoints were assessed using records.


Between January 2000 and September 2020, a total of 397 phase II trials were registered in, investigating 167 agents and 96 targets. Of the 167 agents investigated in phase II, 28 were steered towards phase III, after three phase II trials on average. Repurposed drugs were less likely to advance in clinical development than drugs developed specifically for AML. Composite response endpoints were the most prevalent primary endpoints in phase II. Of the eight FDA-approved targeted drugs, none had investigated quality of life at time of approval, and three out of eight have yet to show benefit in overall survival. 


Despite all efforts, returns on targeted therapy research remain lean for AML patients. Future trials should therefore not solely focus on targeted drugs and foremost study endpoints that improve patient well-being.