MRD Monitoring May Help Redefine Long-Term Goals in Myeloma Therapy
MRD Testing Guides Multiple Myeloma Treatment Decisions
Updated June 2, 2025
Minimal residual disease (MRD) testing is increasingly importent in managing multiple myeloma, an incurable blood cancer. Experts at the 2025 ASCO Annual Meeting discussed using MRD to tailor treatment strategies for patients. The goal is to use MRD, a key indicator, to determine the best treatment approach.
MRD refers to the small number of cancer cells remaining after treatment, undetectable by standard tests. It’s measured using next-generation flow cytometry (NGF) and next-generation sequencing (NGS) on bone marrow samples. These methods can detect as few as one cancer cell among 100,000 normal cells. research into detecting MRD in peripheral blood is ongoing.
A negative MRD test means no disease is detected, while a positive result indicates remaining cancer cells. Experts suggest using an MRD negativity threshold of less than 10⁻⁵ or 10⁻⁶ to guide treatment. MRD status can inform decisions about reducing or stopping treatment and managing any resurgence.
The International Myeloma Working Group first published international response criteria for multiple myeloma in 2006, then updated them in 2016 to include MRD assessments. The FDA authorized a clonal acidic assay for detecting residual disease in 2018. In 2024, an advisory committee supported using MRD for accelerated approval of new myeloma treatments, defining MRD as 10⁻⁵ at 9 and 12 months.
MRD negativity can help decide about maintenance therapy, transplant, and treatment reduction. Standard-risk patients with MRD negativity tend to have better outcomes.The ATLAS trial showed that patients who were MRD-negative after six cycles of carfilzomib could safely stop treatment while maintaining good results. The trial compared carfilzomib with lenalidomide and dexamethasone in standard-risk patients. Those who stopped carfilzomib did better than those on lenalidomide alone.
“So, we can give time-related courses of therapy, use MRD to guide our decision-making, and still get to a better point than where we started,” said Benjamin Avi Derman, MD, from the University of Chicago.
Lenalidomide, a standard maintenance therapy, presents challenges like side effects and financial burden. Derman noted that lenalidomide maintenance often continues indefinitely, impacting quality of life and perhaps causing second cancers. He added that the drug typically costs $18,000 a month in the U.S.
The MRD to MRD2STOP study evaluated patients who stopped treatment based on MRD status, showing that 68% remained MRD-negative three years later, and 85% were alive without progression. The trial was designed to observe the natural history of MRD changes, finding that some patients who became MRD-positive later returned to MRD-negative.
MRD resurgence, the reappearance of myeloma cells after a period of MRD negativity, is most common three to four years after doublet therapy. However,not all resurgences lead to clinical progression.
Neha korde, MD, from Memorial Sloan kettering Cancer Center, explained that in a Greek discontinuation study, about a third of patients who restarted lenalidomide maintenance after MRD resurgence still progressed clinically, while two-thirds remained asymptomatic.
MRD resurgence after quadruplet therapy appears more concerning, with a shorter time to progression. Achieving MRD negativity post-transplant remains a key milestone, but the possibility of resurgence highlights the need for careful monitoring.
What’s next
MRD assessment is expected to play a larger role in guiding treatment decisions, but more research is needed to determine how MRD status shoudl inform treatment intensity and duration.Incorporating MRD as an endpoint in clinical trials will be essential to validate its clinical utility and drive the growth of less invasive testing methods.