Daratumumab Shows Promise in Treating Multiple Myeloma Relapse

By Alice Smith | MILAN – 2025/06/15 02:20:12

Early use of daratumumab (Darzalex) in multiple myeloma patients experiencing minimal residual disease (MRD) relapse extends the time before the disease progresses and can restore MRD negativity in many patients. These findings come from the PREDATOR-MRD trial (NCT03697655), which were presented at the 2025 European Hematology Association Congress.

After a median follow-up of 17.9 months (range, 2.6-33.3), the median event-free survival (EFS) wasn’t reached in the treatment arm but was 9.5 months with observation alone (HR,0.20; 95% CI, 0.05-0.76; P = .0097). Significant paraprotein relapse (SPR) or clinical relapse occurred in 12 patients, with 3 receiving daratumumab and 9 in the observation arm.

Notably, 75% of patients re-achieved MRD negativity. During cycle 3,patients 1 to 7 were MRD negative,and patients 8 through 12 were MRD positive. in cycle 10, 4 patients were MRD negative, 7 were not assessed, and 1 had progressive disease. By cycle 17, 3 patients were MRD negative, 5 were not assessed, 2 had progressive disease, and 1 had a timepoint that was not reached.

Expert Insights on MRD Monitoring

“MRD monitoring every 4 months allows detection of MRD relapse before any biochemical progression in 75% of patients,” said krzysztof jamroziak, MD, PhD, from the Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, during the presentation.

“MRD monitoring every 4 months allows detection of MRD relapse before any biochemical progression in 75% of patients.”

dr. Jamroziak added, “PREDATOR-MRD results can serve as proof of concept for larger trials with novel MRD assessment techniques and therapies.”

The study included adults with multiple myeloma who had completed one or two prior lines of therapy and achieved a complete response (CR) with MRD negativity. These patients were monitored for MRD reappearance over 24 months,with assessments every 4 months.

Patients who were MRD positive without SPR or clinical progression were randomly assigned 1:1 to receive daratumumab at 16 mg/kg intravenously or 1800 mg subcutaneously weekly for 8 weeks, twice weekly for 16 weeks, and monthly for 48 weeks or until SPR or clinical progression. The observation arm involved regular study visits every 4 weeks.

The primary endpoints were EFS and time from randomization to SPR, clinical relapse, or death. Secondary endpoints included time from MRD reappearance to SPR or clinical relapse in the control arm, efficacy of daratumumab in the treatment arm, safety, and quality of life. The exploratory endpoint was the MRD-negativity rate in the daratumumab arm on day 1 of cycle 3.

Among the 54 patients in the MRD reappearance observation phase, 61.1% were female, the median age was 59 years (range, 45-70), and 53.7% had an ECOG performance status of 0. international Staging System (ISS) scores included I (35.2%), II (20.4%), III (22.2%), and missing (21.1%).A total of 51.8% of patients had an MRD positivity rate, 4 patients had concurrent SPR and were excluded, 3 patients had positive immunofixation electrophoresis (IFE), and 21 patients had a pure MRD recurrence. The median time to MRD recurrence was 20.8 months (95% CI, 12.4-23.8).

In the randomized treatment (n = 12) and observation (n = 12) arms, 66.7% vs 66.7%, respectively, were female, the median ages were 57 years (range, 44-68) vs 63 years (range, 47-70), and most had an ECOG performance status of 1 (33.3% vs 75.0%). ISS scores included I (25.0% vs 33.3%), II (25.0% vs 33.3%), and III (33.3% vs 25.0%). The cytogenetic profile included standard risk (41.7% vs 25.0%) or high-risk (25.0% vs 16.7%). The number of prior lines of treatment was 1 in each arm, the median time from diagnosis to randomization was 36.3 months vs 34.9 months, and the median time from last treatment to randomization was 26.9 months vs 24.5 months.

Safety and Adverse Effects

in the treatment arm, no patients experienced grade 3 or higher adverse effects.All hematologic AEs included anemia (8.3%), lymphopenia (8.3%), and neutropenia (8.3%). No hematologic AEs occurred in the observation arm.

The most common non-hematologic aes included upper respiratory tract infection (50.0% vs 0.0%), urinary tract infection (16.7% vs 8.3%), other infection (25.0% vs 25.0%), musculoskeletal pain (41.7% vs 8.3%), and polyneuropathy (25.0% vs 0.0%).

Daratumumab had no significant effect on the Global Health Score (P = .59).