Considering MRD Before HSCT for Patients With Acute Myeloid Leukemia

In a debate at the 2023 Great Debates & Updates in Hematologic Malignancies conference in New York, New York, Richard Stone, MD, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, discussed the role of measurable/minimal residual disease (MRD) when considering hematopoietic stem cell transplantation (HSCT) for patients with acute myeloid leukemia (AML.)

The topic of debate was “MRD+ patients with AML should proceed with HSCT,” and Stone argued that they should not. The opposing side was argued by Andrew Artz, MD, MS, City of Hope, Duarte, California. 

Transcript:
 
Hello, my name is Richard Stone and I'm a leukemia doctor at Dana-Farber Cancer Institute in Boston, Massachusetts. I'm pleased to be here today at Great Debates to talk about the role of measurable residual disease, or minimal residual disease, often termed MRD, in AML. I'll be debating Dr. Artz about whether or not one should transplant a patient who has MRD after initial therapy.

Let me give you a little background on this. This is a very controversial topic in our field. Historically, we've given initial therapy to patients with AML called induction therapy, the purpose of which is to reduce the leukemia burden from about 1012 cells at diagnosis, down to about 10^9 cells at the time of remission. That's still a lot of cells, but at 10^9 cells, a bone marrow test and a blood test might be completely normal, under the microscope, that is to say.

But of course, we have many more sensitive techniques to detect residual leukemic cells, which we know are present. We've known that for years because if you stopped the treatment of a patient after 1 cycle or 2 cycles of chemo, the disease will invariably relapse, whereas if you give more cycles of chemo or a transplant, you have a chance to cure the patient. 

So, now we can tell who's a good responder. That is to say, we can't detect their disease by flow cytometry, NGS [next-generation sequencing] or PCR [polymerase chain reaction] if they have a mutation that can be looked at in that fashion. And we can also be very happy if the patient is negative by the current technologies. They have a low, but not zero, chance to relapse.

One thing we definitely know is that it's always better to be MRD-negative by any of these techniques, or hopefully all of them, than be MRD-positive. So if you're presented with a patient who gets 1 or usually 2 cycles of chemo, either 2 induction cycles or 1 induction cycle and 1 consolidation cycle, and they still have detectable disease by one of these techniques, what do you do? 

My contention is that they should be treated with additional therapy prior to a transplant, before going through a transplant, because we know the outcomes when you go into a transplant with MRD-positive disease are not good at all. 

So, I would like to improve the outcomes, [to] prevent relapse after the transplant. Who wants to go through a transplant and then relapse after the transplant? That's horrible. My point will be that we need to erase the MRD with some new therapy. 

Now, of course, the problem is, that will be justifiably raised by my opponent in the debate, is that [in treating] AML, we don't yet have a good what I would call an “MRD eraser.” We do have that in ALL—it's called blinatumomab. Blinatumomab is now routinely used in MRD, and for that matter, MRD-positive, and for that matter, MRD-negative disease.

We're hoping to get something like that in AML, but I'd like to look to the near-term future and believe we'll have such an MRD eraser which should be used. Right now, we can use things like azacitidine and venetoclax to try to do this imperfectly, albeit that's true, but we can still try and get a patient in a better shape before they go to a transplant. And of course, it's also true that we don't know if erasing the MRD is going to affect the benefit. We hope it will. But it's the most we can do with the patients right now. 

And that's why I'm going to be arguing that we should do something if MRD is present after initial chemotherapy. Thanks so much for listening.

Source: 

Stone, R. Debate - MRD+ patients with AML should proceed with HSCT - No. Presented at Great Debates & Updates in Hematologic Malignancies Conference; April 13-15, 2023; New York, NY.