PERSEUS and ADVANCE Updates: Evolving Approaches to MRD-Driven Myeloma Care

EP: 1.Treatment Approaches and Goals: Transplant-Eligible vs. Transplant-Ineligible Patients

EP: 2.The Role of ASCT in Frontline Myeloma: Comparative Risks and Benefits with Other Standard Treatment Approaches

EP: 3.Evaluating First-Line Treatment Options: Quadruplet vs Triplet Regimens and NCCN Guidelines

EP: 4.The Role of MRD Status in Post-ASCT Treatment Decisions and Clinical Integration

EP: 5.Tailoring Maintenance Therapy by Patient Risk: Lenalidomide Alone vs Combination Approaches

EP: 6.Balancing Timing of ASCT: Insights on Delayed Transplantation and Long-Term Treatment Outcomes

EP: 7.Managing Early Relapse in Transplant-Eligible MM and the Influence of Clonal Evolution

EP: 8.Advancing Frontline Therapy in Transplant-Eligible Myeloma and Emerging Trends in Smoldering Myeloma Management

EP: 9.Evolving Treatment Strategies in Transplant-Ineligible NDMM: Expert Insights From CEPHEUS, IMROZ and BENEFIT

EP: 10.Navigating First-Line Therapy Guidelines and Treatment Considerations in High-Risk Cytogenetics

EP: 11.Balancing Deeper Response and MRD Negativity With Toxicity Risks in Clinical Decision-Making

EP: 12.Therapy Selection and Management Strategies for Transplant-Ineligible Older Patients

EP: 13.Expert Perspectives on Balancing QOL, Convenience, and Depth of Treatment Response

EP: 14.Key Takeaways From CEPHEUS: Subgroup Analysis

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EP: 15.PERSEUS and ADVANCE Updates: Evolving Approaches to MRD-Driven Myeloma Care

The PERSEUS trial subgroup analysis revealed that patients achieving minimal residual disease (MRD) negativity consistently demonstrated superior long-term outcomes, with the concept of “rich get richer” applying across different response depths and time points. A key innovation in PERSEUS was the emphasis on sustained MRD negativity and treatment de-escalation, with daratumumab maintenance discontinued at 2 years for patients maintaining MRD negative status. This approach provides a framework for achieving treatment-free intervals even within continuous therapy models.

The advanced trial studying carfilzomib, lenalidomide, and dexamethasone with or without daratumumab showed a 2.5-fold increase in MRD negativity rates at 10^–5 level with the 4-drug regimen. This trial allowed for optional transplantation based on patient response, representing a flexible treatment approach that accommodates individual patient circumstances and preferences while maintaining high efficacy standards.

Comparative modeling between PERSEUS and CEPHEUS trials suggests significantly different progression-free survival outcomes (PFS), with transplant-containing regimens potentially offering 17- to 20-year median PFS compared to approximately half that duration for non-transplant approaches. These findings highlight the continued importance of autologous stem cell transplantation in appropriate patients while supporting intensive therapy for those unable to undergo transplantation. The data emphasizes the need for careful patient selection and individualized treatment planning.