New drugs for acute myeloid leukemia inspired by genomics and when to use them

Abstract

We are several years into the "postdiscovery" era in acute myeloid leukemia (AML) thanks to extensive work involving the sequencing of genomes and exomes of countless patients, which has led to routine comprehensive targeted sequencing in clinical care. The ability to unlock the molecular underpinnings of each patient's disease was supposed to usher in a new treatment era in which each patient was assigned, based on her mutational profile, a personalized cocktail of targeted therapies that would snuff the disease into submission with minimal toxicity. Whether we have fully realized the promise of personalized therapy in AML is unclear. Here, I review those new drugs that have been inspired by genomics, discuss others that might be possible and their potential roles, and consider whether the ability to target genomic mutations in a personalized manner constitutes the future of AML therapeutics or is representative of an era that has already passed.

Figure 1.

Timeline of 10 years of genomic profiling in AML patients accompanied by major breakthroughs in genomically inspired targeted therapies. IDH1 and IDH2 are the only genes to have major drug development advancements in the era since the first AML genome was sequenced. Blue lines represent drug development milestones, and red lines represent genomic advances.