Eckfeldt Looks Towards the Future of AML and MDS Care

Craig Eckfeldt, MD, PhD

As research in acute myeloid leukemia (AML) continues to pick up ground, examining approaches targeting menin and TP53 mutations are top of mind for investigators to push for further progress, according to Craig Eckfeldt, MD, PhD.

The role of minimal residual disease (MRD) testing is also an area of interest in myelodysplastic syndromes (MDS) and AML, with investigators noting in a paper published in International Journal of Molecular Sciences that a combination of phenotypic and molecular techniques appears to be the most reliable way to allow for optimal MRD monitoring.

“The growing number of markers that can be used to evaluate MRD are going to continue to expand both as a tool for evaluating disease but also for clinical decision making [in] improving outcomes and knowing who needs more or less [therapy]. Risk stratification is a big deal and is having a major impact,” Eckfeldt said in an interview with OncLive®.

In the interview, Eckfeldt, an assistant professor of Medicine in the Division of Hematology, Oncology, & Transplantation, at the University of Minnesota and an attending physician at M Health Fairview Cancer Care in Minneapolis, Minnesota, discussed key updates in AML and MDS from a recent OncLive State of the Science Summit™ on hematologic malignancies that he participated in.

OncLive: What are the implications of MRD testing in AML?

Eckfeldt: In many hematologic malignancies [and] cancers more broadly, the ability to detect smaller amounts of MRD is changing the landscape; for acute lymphoblastic leukemia it has played a large role in prognostication and goals for treatment. In AML it’s lagged behind, but now with modern technology [and] the improvement in the multiparameter flow cytometry—and even more so with some of the genetic-based tests [such as] PCR-based testing that can get down to such low levels—[MRD testing has] become an important end point for looking at new approaches.

Also importantly, there’s experience using MRD as a marker prior to transplant [as well as] post-transplant, and [in] helping to determine [treatments] for patients who classically may [have] a favorable risk-type of leukemia. We know that not everybody who has favorable features, even if they achieved the traditional goals of therapies, patients relapse and being able to determine who will be more likely to relapse and may require more intensive treatments or novel approaches has revolutionized [care].

What are some recent key updates to the MDS treatment paradigm?

The improved understanding of the pathophysiology of diseases such as MDS has allowed for the development of therapies that more specifically target the driving factors. For lower risk MDS, agents such as luspatercept-aamt [Reblozyl] have provided a whole new avenue of treatments in a situation where traditional therapies such as erythropoietin may not have been as effective. Molecular markers [that can] guide decision making have been a major advance.

[In] AML some of the work has clearly defined [that] there are some subsets of [patients with] MDS [with] bad prognostic markers. We’ve learned a lot about who’s not going to do well, but there’s a huge need to figure out how we can try to change that trajectory and improve outcomes.

[Additionally], although there are novel therapies that have had a lot of encouraging results [in MDS and AML], the subset of patients [with TP53 mutations] still struggles. There’s interest in figuring out ways to target TP53, [and] hopefully in the coming years there will be new approaches that are going to have more meaningful impacts on patient outcomes.

What emerging agents are notable in relapsed or refractory AML?

There’s been a lot of interest in targeting menin in AML and a lot of the preclinical work over the past 10 to 15 years has been very interesting—it’s nice to see that start to make its way into clinical investigation [with menin inhibitors]. Some early results suggest that this may be one of the next lines of treatment for particular subgroups, [such as in patients in] high risk subgroups of AML who have not had approaches with the impacts that we’ve been looking for.

As we start to get more results from some of these early phase trials, those are going to be some of the most interesting things to see. The preclinical data are very encouraging, but how is that going to translate into clinical practice? There are some encouraging early results, but they’re early, so following those and seeing where that takes the next steps [in treatment] is going to be very exciting.

What key questions need to be answered next in AML?

There’s a lot of room to continue to look at which subgroups are going to benefit the most by targeting particular pathways; whether targeting [multiple mutations or pathways] in combination could be a safe and more effective way to try to [treat patients is under evaluation]. AML may be lagging behind in relation to some of the other hematologic malignancies with immunotherapies, and CAR T-cell therapy and other immunomodulatory or immunotherapy-based approaches [have] a lot of interest. But, unlike some of the lymphoid malignancies and myeloma where those [approaches] have gained more traction, there’s a lot of room for growth. Hopefully we can find ways to take advantage of those approaches to improve the lives of patients with AML.

I was so glad to be able to be part of the State of the Science Summit; with the increasing complexity [of] the new treatments for hematologic malignancies that have revolutionized how we’re approaching these [diseases], it’s evolving rapidly and is more complicated now than before. To be able to get together with my academic colleagues and try to wrestle with some of these questions but also to work with our community physicians to help try to figure out [treatment strategies is important]; teamwork does make the dream work.

We need to be able to work together [and] help educate [each other]; a lot of people can’t be or aren’t being treated in an academic center. Helping to figure out how community physicians work closely with academic centers [and] knowing when to communicate, how to communicate, when to refer patients, and continuing to provide that platform to get the cutting-edge information out there is key. It was a real pleasure to be able to be part of that [conversation].

Reference

Chea M, Rigolot L, Canali A, Vergez F. Minimal residual disease in acute myeloid leukemia: old and new concepts. Int J Mol Sci. 2024;25(4):2150. doi:10.3390/ijms25042150