MRD End Point Brings “Positive Change” to Multiple Myeloma Research

In April 2024, The FDA’s Oncologic Drugs Advisory Committee (ODAC) voted in favor of minimal residual disease (MRD) negativity as an end point to support the accelerated approval of novel treatment regimens for patients with multiple myeloma. More than 2 years following this decision, experts in the multiple myeloma field are continuing to adopt new strategies of investigational drug development to give patients access to new therapies as soon as possible.

Muhammad U. Mushtaq, MD, spoke with CancerNetwork^® about how this regulatory decision has influenced his work in multiple myeloma as well as efforts from those across the field. He noted that challenges persist in optimally sequencing newly available cellular therapies, especially among certain patient subgroups who experience worse outcomes.

The availability of MRD as a surrogate end point for longer-term survival, Mushtaq said, is a “positive change” that eliminates a need for 5 to 10 years of additional follow-up for mature data to influence treatment decision-making. The ODAC’s vote in favor of MRD has led Mushtaq and other investigators to incorporate it as a surrogate end point for many future trials.

Mushtaq is an associate professor of medicine in the Division of Hematologic Malignancies and Cellular Therapeutics of the Department of Medicine at the University of Kansas Medical Center.

Transcript:

This will influence a lot of the maintenance studies and sequencing studies. A lot of myeloma drug development has focused on development of newer drugs recently, and we have had great drugs approved in recent years, including CAR T-cell therapies and T-cell–engaging therapies. We lack guidance on how to best sequence those. What is the right place to use different drugs that are now available to treat myeloma? [Considering] the myeloma burden, extramedullary disease, or functionally high-risk—that’s essentially defined as progressing within 2 years of primary treatment—or high-risk myeloma per IMWG criteria, there are specific subsets of [patients with] myeloma who still do poorly. Do we need to do differently in those patients?

MRD negativity gives us a surrogate end point, especially at 2 years. Two years of sustained MRD negativity or 2-year PFS will eventually into survival benefit, and we don’t have to wait 5 to 10 years [for a] read out to change treatments. It is a positive change. Many of the future research and clinical trial investigations, including my own [and] investigator-initiated trials, are now looking at 2-year or 1-year sustained MRD negativity as a surrogate end point.

Reference

April 12, 2024 Meeting of the Oncologic Drugs Advisory Committee (ODAC). Streamed live April 12, 2024. Accessed April 20, 2026. https://tinyurl.com/2tbe3f4k