Dr Abdelhakim Discusses NGS To Detect MRD Before HSCT in AML

Haitham Abdelhakim, MD, University of Kansas Medical Center, discusses a meta-analysis on using next-generation sequencing (NGS) to detect measurable residual disease (MRD) in patients with acute myeloid leukemia (AML) undergoing hematopoietic stem cell transplantation (HSCT); the data of which were presented at the virtual 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

Transcript

Hi, my name is Haitham Abdelhakim. I'm a bone marrow transplant and leukemia physician at the University of Kansas Medical Center in Kansas City, Kansas.

AML is an aggressive kind of cancer. Many of the patients have to undergo an allogeneic hematopoietic stem cell transplant to, hopefully, achieve a cure.

However, many of these patients can still relapse after this intensive treatment. It's of paramount importance to identify patients who can relapse after this kind of transplant, so we can know better what to do for them. That can help the discussion before going through this intensive treatment for risks and benefit for these patients.

There are classical risk factors for relapse after hematopoietic stem cell transplant for patients with AML. Mainly, cytogenetic risks and some molecular risks. I did find a MRD which is beyond classic complete remission has emerged as an independent factor for relapse after the transplant for patients with AML.

The problem is there is heterogeneity in the methodology to detect MRD. Those are our PCR. They're our flow cytometry methods and targeted next-generation sequencing, or NGS, which will be focusing on within our study.

We utilize this specific methodology, the NGS, because it has advantages over the multiparametric flow cytometry in PCR. It can be more sensitive because it looks at different multiple gene variants at the same time at good depths that help us identify the patient with MRD.

This has emerged in several studies as a risk factor for relapse either after induction diagnosis or after HSCT. We pursued looking at these kinds of studies in a meta-analysis form because most of these studies didn't include a large number of patients.

In our study, we searched the literature for old studies that included MRD before allogeneic HSCT for patients with AML and its effect on relapse and other outcomes after the transplant.

We have identified 6 studies that were able to have all the inclusion criteria that we predetermined with a total of more than 700 patients. We think that gives us good data about the association of outcomes post-transplant for patients with AML and the presence of MRD.

As not surprising, we were able to show that there is significant hazard ratio (HR) for relapse of the disease after the transplant for patients who had MRD by NGS only. That was a hazard ratio of 2.5.

That wasn't only associated with an increased risk for relapse, but it was associated with leukemia-free survival, and also, worse overall survival (OS) with a HR of 1.6. That was independent of the classical cytogenetic risk, and also, the conditioning chemotherapy or chemoradiation the patient received prior to the transplant.

NGS is being used more and more in many centers in the US and around the world as a method for risk stratification at the start of their treatment and at diagnosis. I think one thing we can look for is repeating these studies to look at how deep this remission is for the patients who are in remission that can help us identify a group of patients who is high risk for relapse independent of their classic cytogenetic risks.

That can help in discussion with patients prior to undergoing such an intensive therapy as an allogeneic HSCT, so they know the risks and the benefits of going through this.

Second, it can help guide clinical trials in the future for designing certain intensity for the stem cell transplant conditioning or other ways to get relapse where the patient was a high risk of relapse, which is undergoing.

The way we want to expand on this research is that any clinical trial that we design or help in designing, that we look at the NGS as a powerful tool for depicting MRD for patients with AML for transplant and help answer questions like, do the patient with negative MRD read a highest intensity of condition for transplant?

That's one question. A second question is, for a patient with positive MRD, what else can we do for this specific group of patients to mitigate the risk of relapse?