Daratumumab or active observation for asymptomatic biochemical relapse in patients with multiple myeloma.

The progression pattern of multiple myeloma is heterogeneous and often characterised by asymptomatic biochemical progression preceding the onset of organ-related symptoms. It is unknown whether pre-emptive treatment of biochemical progression can affect long-term outcomes. The PREDATOR-BR trial is a randomised, multicentre study that enrolled 92 patients who met criteria for biochemical progression but not the criteria for significant paraprotein relapse (SPR). The participants were assigned to either daratumumab monotherapy or observation. The primary end-point was event-free survival (EFS), defined as the time until clinical relapse, SPR or death from any cause. At the prespecified interim analysis with a median follow-up time of 16.7 months, the median EFS was 28.9 months with daratumumab and 4.0 months in the observation arm (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.14-0.43). The response rate was 61.0% in the treatment arm and 6.8% in the observation arm (p < 0.0001). The 24-month overall survival was 100% in the treatment group and 70.5% in the observation group (HR, 0.04; 95% CI, 0.00-0.34). Treatment was associated with manageable safety and no deterioration in quality of life. These results suggest that early treatment initiation during asymptomatic biochemical relapse of multiple myeloma may delay clinical relapse and prolong patient survival.