Advances in patient care through increasingly individualized therapy

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.

Key advances

• 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 therapy^2,3,4.

• 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 ongoing^7,9.

• 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.