Benefits of HSCT for Patients With AML With MRD After Initial Therapy

In a debate at the 2023 Great Debates & Updates in Hematologic Malignancies meeting in New York, New York, Andrew Artz, MD, MS, City of Hope, Duarte, California, highlighted the benefits of hematopoietic stem cell transplantation (HSCT) among patients with acute myeloid leukemia (AML) with measurable residual disease (MRD) after initial therapy. 

The topic of debate was “MRD+ patients with AML should proceed with HSCT,” and Artz argued that they should. Artz debated this topic with Richard Stone, MD, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. 

Transcript: 

Well, thank you for the opportunity to go over the debate we had today. My name is Andy Artz from the City of Hope. I'm a Professor of Hematology and Stem Cell Transplant. I debated Dr Richard Stone, who's a professor at the Dana-Farber Cancer Institute. We can go over a few of the key points we discussed today. 

There was some agreement between Dr. Stone and I, and first was the challenge of measuring MRD, or measurable residual disease. There are a lot of different assays, and it's important to know the assay that we're studying, because there are differential impacts on outcome depending on how we assess MRD.

It's clearly established that MRD positivity after induction, for most patients, leads to higher rates of relapse and poor outcomes without transplant, and sometimes in the setting of transplant. There's some exceptions to that, especially the chip type mutations, DNMT3A, TET2, and ASXL1 may not necessarily confer the same high risk of relapse when MRD-positive just for those genes. 

And then comes the most difficult question: should an AML patient who has MRD positivity pursue transplant? We have the caveat that the patient would have to be immediately ready for transplant, have a donor, and be a candidate. And that isn't always the case. 

But most of the time, for patients who are MRD-positive that we think there is a higher risk of relapse based on that disease, if they can pursue transplant, we will try to pursue transplant— knowing that even then we don't entirely mitigate the higher relapse risk with MRD.

We both showed data that suggests that at least for some patients who are MRD-positive, particularly the NPM1-positive younger patients, higher intensity regimens may mitigate, to some extent, the higher relapse risk that would be seen if they were offered reduced intensity transplant regimens. 

A lot of our patients, though, are older, and can only handle reduced-intensity regimens. Both of us struggle with the value of MRD and our older patients after considering the baseline genetic risks, because higher genetic risk patients, in and of themselves, define in some ways the relapse risk after transplant. Thus, higher-risk patients at baseline have higher relapse risk, and MRD—it's not as clear how much it adds to risk stratification.

There's some emerging data that a melphalan-based reduced intensity regimen, so a little more intensive regimen, may be a way to reduce relapse risk over other reduced intensity regimens, but that's entirely retrospective. 

I think the conclusion is that we don't have definitive data. We try to pursue transplant for MRD-positive patients in the large part, but we all agree that we need better assays, and we need better studies to understand how better to manage these patients. So, I want to thank you for the chance to discuss our topic. 

Source:

Artz, A. Debate - MRD+ patients with AML should proceed with HSCT - Yes. Presented at Great Debates & Updates in Hematologic Malignancies Conference; April 13-15, 2023; New York, NY.