Impact of MRD negativity on QoL

With the introduction of quadruplet regimens in the frontline treatment of newly diagnosed multiple myeloma (NDMM), achieving minimal residual disease (MRD) negativity has become an attainable goal for a growing proportion of patients. However, until now, limited evidence has been available regarding the impact of MRD negativity on the quality of life (QoL) in this population.

At the 2025 IMS meeting, Prof Dr Jesús San-Miguel, haematologist at the University of Navarra Clinic, presented a new analysis evaluating the impact of MRD negativity on patients treated in the pivotal PERSEUS and CEPHEUS studies. In these trials, patients were randomized to receive either daratumumab, bortezomib, lenalidomide, and dexamethasone (DVRd) induction/consolidation followed by daratumumab and lenalidomide (DR) maintenance, or the standard regimen of bortezomib, lenalidomide, and dexamethasone (VRd) with lenalidomide (R) maintenance (PERSEUS), or DVRd vs. VRd alone (CEPHEUS).

Across both studies and treatment arms, patients who achieved MRD negativity experienced improved progression-free survival (PFS) compared to those who remained MRD positive. Notably, although the median treatment duration was longer for patients achieving MRD negativity, treatment-emergent adverse events (TEAEs) were consistently less frequent in DVRd-treated MRD-negative patients than in their MRD-positive counterparts.

Importantly, patient-reported outcomes, as measured by the EORTC QLQ-C30 global health status scale, were at least as favourable in MRD-negative patients treated with DVRd compared to those who remained MRD positive, suggesting that deeper responses did not come at the expense of QoL.

In conclusion, this is the first report to demonstrate that NDMM patients who achieve MRD negativity with DVRd not only benefit from longer PFS but also experience a more favourable safety profile (adjusted for treatment exposure) and maintain QoL. This underscores the value of MRD negativity as a meaningful treatment goal in the era of quadruplet frontline therapy.