The changing landscape of AML

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Published: 20 Jun 2019
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Prof Torsten Haferlach - MLL Münchner Leukämielabor GmbH, Munich, Germany

Prof Torsten Haferlach speaks to ecancer at the 2019 European Hematology Association (EHA) Annual Meeting about the changing landscape of AML.

He provides some examples of new drugs for specific patients, and advises physicians to treat AML as many different diseases which need to be individually examined.

ecancer's filming has been kindly supported by Amgen through the ecancer Global Foundation. ecancer is editorially independent and there is no influence over content.

 

The landscape of AML is changing rapidly right now; this is for several reasons. First of all, we learnt much more about the molecular and the genetic background of AML in the last ten to even five years only and, second, there are already some new drugs available, they have FDA approval or EMA approval and there are many more drugs coming. This together makes a big change for patients suffering from AML from the diagnostic point of view and also from the treatments that can be applied. Let’s call it more and more precision medicine.

What are some of these precision medicines?

We face now the situation if we pick up at diagnosis some specific mutations or expression of some genes that can be used for specific treatments. For example, one is FLT3-ITD or FLT3-TKD, these are changes in the respective gene you can pick up by sequencing. There are now drugs already approved in first line treatment like midostaurin or in the relapsed situation that can be applied to patients with AML and that are completely focussing on the respective marker that has been changed in the leukaemia cell.

In addition, we see drugs that we know already and now can be used again like gemtuzumab ozogamicin that address a specific surface antibody on the surface of the AML cells, CD33. Further, there are very, very important changes in the landscape of, for example, BCL2 inhibitors where we see drugs like venetoclax that can already be used in the US for patients that have older age and have an AML with a normal karyotype or a standard cytogenetic profile and not FLT3 mutated in first line. These are huge changes because over the last forty years we normally use so-called 3 7, this is Ara-C and daunorubicin. In addition to that we can now use these drugs like midostaurin or GO or instead of it we can now use venetoclax. This is a very big change for the diagnostic approach but also for the thinking of the doctors to which treatment we refer the patients.

The new drugs will be covered in the session by [??] and there are some additional information on genes and there will be some new ideas how to measure them better in the future. But so far our gold standards are the morphology, the cytogenetics, a molecular genetic panel to address the genes of interest for diagnosis, for prognosis and for specific treatment. We use more and more now information on the NGS level that means we investigate genes with next generation sequencing to get even more information about the prognostic impact of these genes and the respective treatment relevance.

What is your message to clinicians following the EHA meeting?

The most important thing is we more and more realise that AML is not one AML but it’s dividing up into, let’s say, even more than a hundred different parts of this disease, AML. That is important, not only because the patient is 20 or 80 but it is important because they have specific cytogenetic changes, they have specific molecular genetic changes. This all together makes a very big difference. We have to have in mind that from the up-front information at diagnosis there are AML patients that can be cured today without chemotherapy but with ATRA and arsenic in 95%. There are other AML patients from the up-front knowledge of the diagnosis, the cure rate is only 10-15% including allogenic transplantation. So this huge gap between this AML and the other AML is now getting to be closed and we try to lift up especially the high risk patients to an intermediate group by understanding better why they are high risk and by addressing these structures in the leukemic cells that we can over-read with new drugs to make them more intermediate risk.

One important thing that also comes more and more into this field is the measurement of minimal residual disease, or measurable residual disease we call it, that means we follow-up those patients on the basis of the molecular markers we picked up at diagnosis and we see how the treatment works and if we are facing a beginning relapse. Then we can intervene much earlier than, as we waited before, until the blast count is up again.

So all these things together make a really big change in the world of AML today but that also means that we need to investigate all these markers, these genes, these chromosomes before we think about the best treatment to be applied and follow up with MRD.