For a recent PW podcast episode, Matthias Stelljes, MD, of the Department of Medicine-Hematology and
Oncology, University of Muenster, spoke about the randomized Phase 3 ASAP Trial for the management of
relapsed/refractory acute myeloid leukemia (AML) using intensive chemotherapy in advance of allogeneic
hematopoietic stem cell transplantation (allo-HCT).

Should intensive chemotherapy prior to allo-HCT be used in relapsed/refractory AML?

Until now, in patients with refractory disease, intensive chemotherapy
prior to allo-HCT was not considered a standard treatment option. Most of the international centers, as
well as those in the US, would suggest going for another HCT in the case of regular disease control or
better hematological remission. What we are now seeing is that patients with active AML who receive
intensive chemotherapy prior to allo-HCT have a fair chance of getting into remission and staying in
remission for a reasonable time.

Another important message is that, in patients with induction failure or
relapse disease, it is not necessary to perform salvage therapy. However, patients who have relapsed are just one-third
of the entire study population, so salvage therapy can be quite effective. We had a conversion rate with
high-dose chemotherapy of around 50%, but this did not translate into better overall survival for the
entire study population.

What were some of the limitations to this study?

The main limitation is that
when you try to adapt our study to the broader patient population, you need the capacity to perform a
blood transplant as soon as possible. Therefore, you need to have a donor available as soon as a transplant
becomes necessary. In Germany, when we have a patient with newly diagnosed leukemia, a donor search is
conducted at primary diagnosis. We don’t wait until we start thinking about performing a transplant. This
is standard for all patients with leukemia and allows us to perform a transplant as soon as possible. But
this is not the case in many other countries.

What future research is needed?

More randomized trials are needed to test novel agents and novel salvage regimens and compare them with direct transplant. We need to see if novel therapies are better than direct transplant.

What unmet needs remain in AML?

The unmet need is, clearly, that we must improve our treatments to enable more patients with AML to receive a successful transplant.

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