EHA 2021 | Evolution of the AML treatment paradigm

We’re living in an era where treatment paradigms are evolving and changing after many years of stagnation. This is primarily due to two things, better diagnostics, better genomic analysis, and better understanding of prognostic features, and also the emergence of new agents, which have been approved over the last two or three years, starting with gemtuzumab, also three inhibitors, such as midostaurin and gilteritinib, and other agents such as vyxeos, EPX and also more recently venetoclax.

So, this has transformed the landscape. Some of these agents have now become standard of care, but really the upfront diagnostics is crucial, not only cytogenetics, which has been an important diagnostic feature for many years, but also genomic data, which particularly where this can inform early treatment decisions. Some are actionable or very early, so that if, for example, if the patient has a FLT3 inhibitor, a FLT3 mutation, you need to know this within a few days of presentation so that you can access and start appropriate therapy. But some are more important in later decision-making, following achievement or remission, when emerging genomic data from that patient can alter your post-remission management, particularly trying to help the decision about whether a patient should go to transplant in first remission or not. So, the two factors really are improved diagnostics and a greater understanding of prognosis, and the emergence of new agents, which have been incorporated into standard chemotherapy for patients.

And perhaps the greatest benefit emerging is those patients that have been classically called “elderly, unfit”, which we generally mean patients normally over the age of 60, that have co-morbidities or previous illnesses, which might preclude them from intensive therapy. This could be co-existent lung or heart disease, or perhaps extreme age and frailty, and some of these patients, the outcome for these patients has historically been poor. But this is obviously evolving and we’re seeing the application of newer agents, such as venetoclax and IDH inhibitors, and combinations of these, which have transformed the landscape, and we can now offer meaningful treatments to a group of patients for whom there was really very little therapeutic options in the past.