In 2018, the acute myeloid leukaemia treatment landscape expanded notably, with several trials leading to the approval of novel targeted therapies. Furthermore, comprehensive sequencing revealed the effects of co-occurring mutations and gene expression patterns on drug sensitivity, providing hope that future treatments will be increasingly precise and personalized.
The addition of the multikinase inhibitor midostaurin to 7 + 3 chemotherapy for newly diagnosed patients and the use of second-generation fms-related tyrosine kinase 3 (FLT3) inhibitors (such as quizartinib) for those with relapsed and/or refractory (R/R) FLT3-mutant acute myeloid leukaemia (AML) demonstrate improved overall survival (OS) compared with standard-of-care therapy2,3,4.
The oral targeted mutant isocitrate dehydrogenase 1 (IDH1) inhibitor ivosidenib is now approved for the treatment of patients with R/R AML with an IDH1 mutation, as a result of the substantial activity and durable responses seen in a phase I trial5.
In adults with newly diagnosed secondary or therapy-related AML, the liposomal encapsulation of cytarabine plus daunorubicin at a fixed 5:1 molar ratio improved response rates and median OS compared with standard 7 + 3 therapy in a randomized phase III trial6.
The addition of the BCL2-inhibitor venetoclax to lower-intensity AML therapy, such as hypomethylating agents or low-dose cytarabine, for older patients unsuitable for intensive chemotherapy approaches suggests markedly improved patient outcomes; confirmatory randomized trials are ongoing7,9.
Clinical and genomic data from patients with AML, including whole-exome and RNA sequencing, and analysis of ex vivo sensitivity to >100 agents is now freely available and is likely to accelerate and enable future discovery10.
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DiNardo, C. D. et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood https://doi.org/10.1182/blood-2018-08-868752 (2018).
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C.D.D. is supported by The V Foundation for Cancer Research and the MD Anderson Khalifa Clinical Scholar Award.
C.D.D. is a consultant of Abbvie, Agios and Celgene and has received honoraria from Bayer, Jazz, Karyopharm, Medimmune and Syros as an advisory board member. A.E.P. is a consultant for Abbvie, Arog, Astellas and Daiichi Sankyo. Additionally, he has received honoraria from Actinium Pharmaceuticals, Agios, Jazz Pharmaceuticals, NewLink Genetics, Novartis and Takeda as an advisory board member.
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DiNardo, C.D., Perl, A.E. Advances in patient care through increasingly individualized therapy. Nat Rev Clin Oncol 16, 73–74 (2019). https://doi.org/10.1038/s41571-018-0156-2
Glasdegib in combination with low-dose Cytarabine for the outpatient treatment of relapsed or refractory acute myeloid leukemia in unfit patients
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