MRD Assessment Advances Risk Stratification and Treatment Decision-Making in Multiple Myeloma

Clinical Summary: 

• Joshua Richter, MD, examines the evolving role of measurable residual disease (MRD) assessment in multiple myeloma, including its prognostic value, integration into clinical trials, and potential to guide treatment intensification and discontinuation.
• Sustained MRD negativity is strongly associated with improved long-term outcomes, although prospective evidence remains insufficient to support routine treatment modification based solely on MRD status. 
• These findings highlight the importance of integrating MRD assessment with cytogenetics, functional imaging, and patient characteristics to refine risk stratification and support individualized treatment decisions as ongoing trials evaluate MRD-guided treatment strategies. 

Joshua Richter, MD, Ichan School of Medicine at Mount Sinai and Tisch Cancer Institute, New York, New York, discusses the evolving role of measurable residual disease (MRD) assessment in multiple myeloma and its implications for prognosis, treatment selection, and disease monitoring following his presentation at the Lymphoma Leukemia & Myeloma Congress in New York, New York. 

Dr Richter reviews evidence linking sustained MRD negativity with improved long-term outcomes and the growing role of MRD as a surrogate end point in clinical trials and regulatory decisions. He also discusses the limitations of using MRD status alone to guide treatment intensification or discontinuation, highlighting ongoing studies evaluating MRD-directed maintenance strategies and the importance of comprehensive risk assessment in personalizing multiple myeloma care.

Transcript: 

Hi, 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 here in New York and I'm really excited to be at the 2026 Lymphoma, Leukemia & Myeloma meeting, where I had the privilege of debating Ola Landgren about the subject of minimal residual disease (MRD) and what the role is of this type of technology in the clinical management of our patients with multiple myeloma.

We recognize that throughout the years we've discovered that the depth of remission correlates to the durability. MRD negativity, in particular sustained MRD negativity, when it's done 12 or 24 months apart, is really the biggest predictor of prognostic outcome. What has really been amazing is that because outcomes in myeloma have become so prolonged, both in terms of OS and PFS, the FDA has now allowed accelerated approval based on MRD rates. We just saw the approval of iberdomide from the EXCALIBER study based on MRD negativity rates. 

Dr Landgren presented amazing data from a variety of studies showing that the achievement of MRD negativity leads to better outcomes, leads to earlier drug approvals, and has become an integral tool in the management of day-to-day treatment of myeloma patients. 

I had the opposing side, and my standpoint was that although these data are amazing, we don't yet have the prospective data to look at a patient in front of us who's gone from MRD positive to negative and say, "that's good enough to stop your treatment," or gone from MRD negative to positive, and “that's enough to start or intensify your treatment”. 

In reality, although this type of concept has been proven in other diseases such as acute lymphoid leukemia (ALL) with some of the antibody therapy like blinatumomab, in myeloma some of the studies that have sought to intensify therapy based off lack of depth of response, have only led to increased depth of response, increased toxicity, but no clear improvement in outcome of either PFS or OS.

Ultimately what Dr Landgren and I completely agreed on is that MRD is an important facet of the overall assessment of our myeloma patients. We need to use risk stratification, patient age, comorbidities, cytogenetics, along with MRD and functional imaging to better assess where our patients are at and use MRD as a piece of the puzzle to figure out who may be cured and who we can stop therapy on. We also need to look at who may be showing early signs of MRD recurrence and who we may need to intervene early before they have evidence of clinical recurrence of disease.

Overall, really excited to see the next few years of studies, such as the DRAMMATIC study from Arita Krishnan, which will help use MRD to guide when we can stop therapy in the maintenance setting of myeloma, and ultimately using MRD metrics to figure out who is ultimately cured of the disease.