EHA 2025 Insights: ADVANCE and PERSEUS Trial Updates on Daratumumab-Based Regimens for Transplant-Eligible Patients With NDMM

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The PERSEUS trial data demonstrate significant advantages of daratumumab-based quadruplet therapy (D-VRd) over standard VRd in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). The study compared standard VRd followed by transplant and lenalidomide maintenance against D-VRd with transplant and daratumumab-lenalidomide maintenance. Results showed superior MRD negativity rates in the daratumumab arm, with sustained MRD negativity at 24 months being doubled in the experimental arm. The trial data reinforce the importance of transplant in achieving optimal depth of response, with MRD negativity rates at 10–5 reaching 68% when combining quadruplet therapy with transplant consolidation. These findings support the continued role of autologous stem cell transplant in appropriate candidates, even in the era of effective quadruplet induction regimens.

Expert analysis reveals 4 distinct quadrants of transplant-eligible NDMM trials, each evaluating different backbone regimens with transplant consolidation. The PERSEUS trial (D-VRd backbone), GMMG HD7 (Isa-VRd backbone), and GMMG-CONCEPT (Isa-KRd backbone) all demonstrate superior outcomes with quadruplet therapy plus transplant. MRD negativity rates consistently reach 68% to 75% across these studies when transplant is included, highlighting the synergistic effect of intensive induction followed by high-dose consolidation. The consistency of results across different anti-CD38 antibodies and backbone regimens provides strong evidence for the quadruplet-transplant approach as the emerging standard of care for fit patients with NDMM.

The evolution toward quadruplet-based induction regimens represents a paradigm shift in NDMM treatment, requiring careful consideration of patient selection and treatment sequencing. Although MRD-guided approaches such as ADVANCE offer personalized treatment strategies, experts emphasize the proven benefit of transplant in achieving maximal depth of response. The sustained MRD negativity data from PERSEUS at 24 months support the long-term benefits of intensive up-front therapy. Clinicians must balance the promise of MRD-guided therapy with established transplant benefits, particularly for standard-risk patients who may derive substantial benefit from treatment intensification. The integration of these approaches into routine practice will require ongoing evaluation of long-term outcomes and careful patient counseling regarding treatment options.