Should MRD-Based Decision-Making be Utilized in Multiple Myeloma Treatment Strategies?

At the 2024 Great Debates & Updates in Hematologic Malignancies in New York, New York, Joshua Richter, MD, Tisch Cancer Institute, Icahn School of Medicine - Mount Sinai, New York, explores the role of minimal residual disease (MRD) in multiple myeloma (MM) treatment strategies, addressing whether it should be used to make clinical decisions for patients. 

Transcript:

Hello, my name is Dr. Joshua Richter. I'm an associate professor of medicine at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, and the director of myeloma at The Blavatnik Family Chelsea Medical Center at Mount Sinai. 

My presentation at this year's Great Debates [& Updates in Hematologic Malignancies meeting] is regarding the role of minimal residual disease testing and [whether]it [is] ready for primetime use in clinical decision-making. 

With the advent of modern therapies in myeloma, we've been able to achieve remissions we never thought previously possible, able to get patients down beyond the standard measurements of complete remission down to what we call minimal residual disease negative using either next-gen[eration] sequencing or next-gen[eration] sequencing flow cytometry, we're able to rule out the presence of any cancer cells in 1x 10-5 or even 1x 10-6. Really deep remissions.

The question is, are we ready to start using these values to make decisions? As in, if you go to negative or maintain negative, can we stop your therapy? If you go from negative to positive, should we change or resume therapy? Although the state is very interesting, at the current time, we have no data to stand on to use this to make clinical decisions. All that we know at the current time is that if you take two groups of patients, match them [by] age, race, [and] disease, give them identical treatment, and group A achieves MRD negativity, and group B does not. Then, you take the average duration of remuneration. It will be [on] average longer in the group that's MRD negative than those who achieve only MRD positivity. 

Beyond that, we can't say a whole lot more. We have many patients [who] never achieve MRD positivity who continue to do amazing because even though you didn't eradicate their entire disease, what they're left with has what we call a [monoclonal gammopathy of undetermined significance] (MGUS)-like phenotype and sits there for years if not longer.

We have patients who achieve MRD negativity and relapse unfortunately within a short period of time. We begin to understand that there are significantly higher rates of extramedullary disease, and we have patients [who] can still have bulk tumor but when you do a bone marrow biopsy you find no disease and those patients may behave worse than many others. 

Furthermore, we recognize that MRD testing is only one small part of the evaluation of a myeloma patient. We need to look into your risk stratification. Do you have high-risk cytogenetics [or] standard-risk cytogenetics? What does your immune profile look like? What does the microenvironment look like? And so on and so forth. Essentially, it's part of a bigger piece, a bigger puzzle, that MRD is only playing a small role in.

So, although this is fascinating data and there are many great trials ongoing, including the dramatic study, SWOG 1803, led by Dr. Amrita Krishnan (Amrita Krishnan, MD, City of Hope, Duarte, California), that will one day hope to guide us in the maintenance phase of upfront myeloma using MRD to help stratify. At the current time in 2024, we do not have the data to stand on to make true clinical decisions based on MRD status alone. 

Source: 

Richter, J. Debate - MRD Should Guide Therapy - NO. Presented at the Great Debates and Updates in Hematologic Malignancies Meeting; April 5-6, 2024; New York, New York.