What is secondary AML? Is there a difference between secondary AML and therapy related AML? How effective is Vyxeos for people with secondary AML?

What is secondary AML?

Secondary AML is a term that's used to refer primarily to AML that arises from something else. Most often, the most common setting of secondary AML is AML that arises from prior myelodysplastic syndrome. So that's what we often see in cases of secondary AML. Secondary AML can also be considered treatment-related AML in some cases where the AML emerges following prior chemotherapy and/or radiation therapy for a second cancer. It can also be considered secondary AML if it arises from a prior myeloproliferative neoplasm. Now that's not quite as common as when it arises out of MDS or following therapy for other cancers. So those are all the subtypes of secondary AML. But the term secondary AML is becoming a little bit outdated. As we learn more about the molecular features of AML, many of the features of secondary AML are more related to specific genetic abnormalities that are often seen in MDS or myeloproliferative neoplasms, or in the case of therapy-related AML, TP53 mutations.

What is the difference between secondary AML and therapy-related AML?

Well, therapy-related AML is considered a type of secondary AML within the context of other secondary AML subtypes as well, such as secondary AML that comes from MDS or from myeloproliferative neoplasm. So therapy-related AML has traditionally been considered a type of secondary AML.

How are outcomes different for people with primary AML versus secondary AML?

Yeah, traditionally secondary AML is associated with worse outcomes than primary or de novo AML, and that's probably because mostly of the abnormal or adverse genetic features associated with secondary AML, not necessarily just secondary AML by itself. So secondary AML, as I mentioned before, is sort of this conglomerate term for many different types of AML that arise in different settings that often were associated with MDS or myeloproliferative neoplasms. And we know that secondary AML traditionally does more poorly than the de novo AML, but that's not always the case. It depends on primarily the genetic features of the disease and the prior treatment history of the patient as well. So patients that have received prior therapy for, say, myelodysplastic syndrome with drugs like Azacitidine or Decitabine have been clearly shown to have worse outcomes once they develop AML because the drugs for AML just don't work as well. Once a person has already been treated for MDS, which includes many of the same drugs that we actually use for AML.

How effective is Vyxeos for people with secondary AML?

So that is, secondary AML is the primary indication for Vyxeos, and that's the basis that was the basis for its approval by the FDA back in 2017. It’s effective and it induces remission in approximately 50% of patients that receive it as induction therapy. And it is associated with a longer survival than patients who receive induction chemotherapy with 7+3. We found in a phase three study that Vyxeos was able to bridge about one-third of all patients to a transplant, and that the outcomes after transplant in patients who had received Vyxeos as primary induction therapy were better. So that it seems that for some reason that we're not totally clear about, the transplant outcomes are better if patients got Vyxeos as their initial therapy than if they had gotten 7+3.