MRD Recurrence Shown to Precede Biochemical Relapse in Multiple Myeloma

Treating early recurrence of minimal residual disease (MRD) with daratumumab (Darzalex) may offer preferable outcomes and better treatment tolerance vs observation in patients with multiple myeloma who were previously treated with 1 or 2 prior lines of therapy and achieved a complete response (CR) with MRD-negativity on their most recent line of treatment, according to Krzysztof Jamroziak, MD, PhD.

Jamroziak, hematologic oncologist at the Hematology, Transplantology and Internal Medicine Clinic and deputy head of the Clinic for the General Hematology Department of the Medical University of Warsaw at the Institute of Hematology and Transfusion Medicine in Warsaw, Poland, discussed how findings from the phase 2 PREDATOR-MRD study (NCT03697655) support MRD recurrence as a prognostic marker when treating patients with relapsed/refractory multiple myeloma.

He began by highlighting the need for subsequent phase 3 trials to validate the concept of preemptive treatment for early relapse, highlighting a benefit among those who received early daratumumab vs those who underwent observation following initial MRD recurrence. Jamroziak further expressed that MRD recurrence was shown to precede biochemical relapse, with a median time to relapse of 9.5 months in the observation arm. He concluded, given the findings, that earlier treatment may benefit patients more than observation, given a lower disease burden and improved treatment tolerance.

Findings from the phase 2 PREDATOR-MRD trial he presented at the European Hematology Association (EHA) 2025 Congress revealed that the primary end point of event-free survival (EFS) favored 12 patients who had undergone treatment with daratumumab at 16 mg/kg intravenously or 1800 mg subcutaneously vs 12 patients who had undergone observation. The median EFS was not reached (NR, 95%, NR-NR) with daratumumab vs 9.5 months (95% CI, 5.0-NR) with observation.

Transcript:

[Treating] early relapse is important. [Whether it is] biochemical relapse, [or] the previous step, MRD recurrence, it needs to be proven that it is beneficial for patients. [The phase 2 PREDATOR-MRD] study is the first of this construction. It needs to be followed by bigger phase 3 studies proving this concept.

It was proven in the study that MRD recurrence precedes biochemical relapse, and the time for that in the control arm is 9.5 months. It is probably better to treat earlier because the extent of diseases is lower and treatment tolerance is better, and maybe we can end up with MRD-driven shorter treatment. But it needs to be proven for novel therapies.

Reference

Jamroziak K, Kubicki T, Dytfeld D, et al. Daratumumab or observation for minimal residual disease reappearance in multiple myeloma: results from the PREDATOR-MRD randomized trial. Abstract presented at: European Hematology Association 2025 Congress; June 12-15, 2025; Milan, Italy. Abstract S204.