TREATMENTS FOR PEOPLE with multiple myeloma, a type of blood cancer that occurs in the plasma cells of the bone, have extended many patients’ lives. But even in cases where people have a complete response—showing no signs of cancer on imaging or in blood and urine tests—the cancer can return. That’s because multiple myeloma is incurable, and most people with the disease go through cycles of remissions and relapse, followed by rounds of treatment to keep the cancer at bay.

Patients who have a complete response may still have cancer cells in the bone marrow. These isolated cancer cells—called minimal residual disease (MRD)—typically do not cause symptoms, but they are an indicator of future disease relapse. Over the past decade, researchers have developed sensitive ways to detect MRD using tests such as next-generation genetic sequencing from bone marrow samples. After treatment, a person who shows no evidence of MRD—called MRD negativity—typically experiences longer overall survival and more durable remissions than people who show signs of MRD.

In April 2024, 12 experts who were part of the Oncologic Drugs Advisory Committee (ODAC), a panel that evaluates data concerning the safety and effectiveness of drugs for the Food and Drug Administration (FDA), voted unanimously in favor of using MRD testing to determine if a drug being evaluated to treat multiple myeloma should receive FDA accelerated approval.

The FDA already uses measures called surrogate endpoints as criteria to grant accelerated approval for drugs. Surrogate endpoints are measures likely to predict a clinical outcome before there is enough data to confirm established endpoints, such as improved overall survival or quality of life.

For multiple myeloma and many other types of cancer, existing treatments can lead to patients living many years, which lengthens the time it takes to collect data for overall survival outcomes. In these cases, many drugs are assessed using a surrogate endpoint, such as progression-free survival (PFS), which is the time a person lives without cancer progressing. Using MRD negativity to measure treatment effectiveness in a clinical trial could help speed up the approvals further. (Drugs that receive accelerated approval from the FDA still need to undergo confirmatory trials using measures such as overall survival.)

Collaborating with patient advocates and researchers, hematologist-oncologist C. Ola Landgren of the University of Miami Sylvester Comprehensive Cancer Center presented data to ODAC, which led the committee to recommend using MRD negativity as an endpoint for accelerated approval for multiple myeloma drugs. While the FDA has yet to release updated guidance on allowing use of MRD testing, Landgren is encouraged by ODAC’s decision.

He recently spoke with Cancer Today about his efforts to develop standards to measure and assess MRD and how the endpoint could make a difference in bringing new multiple myeloma therapies to patients sooner.

CT: How did the idea to use MRD testing to measure treatment response in patients with multiple myeloma evolve?

LANDGREN: In 2009, I was at the National Cancer Institute of the National Institutes of Health conducting multiple myeloma clinical trials. The drugs we were testing were getting better, and more patients were going into remission for longer periods of time. I saw a need to drill down, beyond just measuring a patient’s response to therapy, to find a more sensitive measure of their disease. I wondered, in the future, how many patients in what we call a “complete response” would remain in remission and how many would relapse? I was also thinking about a future when the majority of patients would respond to treatment, and how we would define a cure. We collaborated with hematologist-oncologists around the world, the FDA and multiple myeloma patient groups to develop a sensitive measure of MRD and defined standards where the presence of MRD means the detection of one cancer cell within 100,000 normal cells.

CT: How did you develop these measures?

LANDGREN: It took 15 years of working with colleagues and compiling the large datasets from different groups and companies that developed multiple myeloma drugs to incorporate MRD testing as a measure of response in multiple myeloma clinical trials. This year, we published an analysis of data from phase II and phase III clinical trials in a peer-reviewed journal. Our large dataset showed us that if a multiple myeloma patient is MRD negative at 12 months after completion of therapy, then that translates into a significantly longer progression-free survival several years later. For more than 10 years, PFS has been used as a regulatory endpoint for full approval by the FDA. Our data shows that MRD negativity is highly predictive of PFS, and, therefore, MRD can be used as an early endpoint for accelerated approval in multiple myeloma.

CT: Does this recommendation by ODAC mean that clinical trials can use MRD as an endpoint and the FDA would have to consider MRD data for accelerated approval?

LANDGREN: The ODAC vote is a recommendation for the FDA to implement MRD testing in multiple myeloma trials, and the FDA typically follows ODAC’s recommendations. There is no precedent for using MRD as an endpoint for accelerated approval. We have been told that the FDA is currently working to implement the ODAC vote by providing written guidance on the use of MRD testing in multiple myeloma trials. Until then, I believe that a company needs to have an agreement with the FDA on using MRD testing as an approvable endpoint in its clinical trial.

CT: If the FDA accepts ODAC’s recommendation to use MRD as an endpoint, what does it mean for patients?

LANDGREN: Today, most multiple myeloma patients who receive modern combination therapy, as part of a clinical trial or not, will achieve a complete response. In my clinic, I see many patients who were diagnosed with multiple myeloma over 10 to 15 years ago and are still doing well. Overall, the myeloma field has come a long way. But there is clearly an unmet clinical need. Unfortunately, we do not yet have an established cure for multiple myeloma, and the majority of patients will eventually relapse. Some patients have adverse disease biology, which makes the disease come back sooner. MRD as an early endpoint for accelerated approval in multiple myeloma will help develop drugs much faster.

This interview has been edited and condensed for clarity.