R/R is the subset of AML with worse long-term outcomes with standard salvage therapies. The investigation of new targeted therapies (IDH and FLT3) has shown promising results, achieving a better antileukemic efficacy and safety profile in comparison with salvage regimens. In this review, we have analyzed the impact of IDH1mut inhibitors, a new targeted therapy with positive results in R/R AML.

Two IDHmut inhibitors (ivosidenib and enasidenib) have achieved fast approval with Phase I/II clinical trial results in the subgroup of IDH1/2mut R/R AML, pending further studies to demonstrate a significant improvement in survival and/or other long-term outcomes. Nevertheless, with the advent of new targeted therapies, the diagnostic workup of R/R AML will now include a systematic screening for IDH1 mutations, in order to personalize treatments. Ongoing clinical trials are testing the use of IDHmut inhibitors as single agent or in combination with HMAs or intensive chemotherapy as frontline therapy and the role of these inhibitors in post-transplant maintenance.


This study was supported in part by a grant from the “Instituto Carlos III” (PI16/00665).


Dr Pau Montesinos reports grants from Celgene and Daiichi Sankyo during the conduct of the study and is on the advisory board for AGIOS, Celgene and Daiichi Sankyo. The authors report no other conflicts of interest in this work.

Juan Eduardo Megías-Vericat,1 Octavio Ballesta-López,1 Eva Barragán,2,3 Pau Montesinos2,3

1Servicio de Farmacia, Área del Medicamento, Hospital Universitari i Politècnic La Fe, Valencia, Spain; 2Servicio de Hematología y Hemoterapia, Hospital Universitari i Politècnic La Fe, Valencia, Spain; 3CIBERONC, Instituto Carlos III, Madrid, Spain


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Source: Blood and Lymphatic Cancer: Targets and Therapy.
Originally published June 27, 2019.

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