Early Treatment with Daratumumab After MRD Relapse May Delay Multiple Myeloma Progression

Minimal residual disease (MRD) is when a small number of myeloma cells remain in the body after treatment. Measuring MRD is a way to predict how well a treatment for multiple myeloma worked.  MRD positivity can indicate that the myeloma may progress in the future, even before symptoms or lab changes appear. If a person who previously tested negative for MRD becomes MRD positive and there are no other signs of cancer, it is called MRD relapse. 

At the 2025 European Hematology Association conference, researchers presented findings from the PREDATOR-MRD clinical trial. This study tested starting daratumumab (Darzalex Faspro, Janssen) at the time of MRD relapse to understand if this could delay disease progression. In this article, you will learn how the study was designed, the main results, and what these findings may mean for patients and their care decisions.

We had the privilege of interviewing Dr. Krzysztof Jamroziak, lead author and presenter of this study. 

The PREDATOR-MRD trial 

The study enrolled patients with multiple myeloma who had completed one or two prior treatments. All participants had achieved MRD-negative complete remission and were not on maintenance therapy. They were regularly tested for MRD every four months for up to two years.

If MRD reappeared but there were no signs of symptomatic relapse or a significant increase in myeloma protein levels, patients were randomly assigned to receive early treatment with daratumumab or observation. 

• Daratumumab treatment group. Participants in this group received daratumumab weekly for 8 weeks, then every two weeks for 8 doses, and then monthly until disease progression or for up to 18 months.
• Observation group. Participants in this group continued MRD monitoring without starting therapy.

The main measure of success was event-free survival (EFS). EFS is the amount of the time from randomization to progression, significant lab relapse, or death.

Key study findings

Between April 2019 and March 2023, 54 patients were monitored for MRD relapse. MRD reappeared in 29 patients after a median of 11.3 months. Of these, 24 patients went on to either receive daratumumab (12 patients) or continue observation (12 patients). In the daratumumab group, median EFS was not yet reached. This means that more than half of patients in this group had not experienced cancer progression, significant lab relapse, or death. In the observation group, the median EFS was 9.5 months. There was an 80% reduction in the risk of an event with daratumumab compared to observation alone. 

In 58.3% of patients receiving daratumumab, MRD negativity was restored after just two months of treatment. 

Mild to moderate adverse events occurred in 67% of patients receiving daratumumab compared to 25% in the observation group. The most common were infections (58% with daratumumab vs 16% with observation) and pain (33% vs 8%). 

 Addressing relapse before it happens 

These findings suggest that starting treatment with daratumumab at MRD relapse, before symptoms develop, may extend the time before progression and restore MRD negativity in some patients. This strategy could provide a way to address myeloma recurrence earlier, but more research is needed to understand long-term benefits and risks.

Patients should discuss MRD monitoring and potential early intervention strategies with their care team. Decisions about starting treatment at MRD relapse depend on individual disease features, overall health, and preferences.

Read more about recent daratumumab updates with this article: Improved Outcomes with Daratumumab Quadruplet Therapy in Newly Diagnosed Multiple Myeloma 

Want to be a part of the myeloma community? Learn more about HealthTree Cure Teams, where volunteers help others and participate in accelerating research to find a cure. 

Get involved with HealthTree, the platform that powers lifesaving research. 

Get Involved

Source: 

DARATUMUMAB OR OBSERVATION FOR MINIMAL RESIDUAL DISEASE REAPPERANCE IN MULTIPLE MYELOMA: RESULTS FROM THE PREDATOR-MRD RANDOMIZED TRIAL