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

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

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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

The CEPHEUS trial represents a landmark study in transplant-ineligible multiple myeloma treatment, comparing quadruplet therapy (daratumumab, carfilzomib, lenalidomide, dexamethasone) versus triplet regimens. This clinical trial specifically addressed the challenging population of older, more frail patients who cannot undergo stem cell transplantation, examining whether adding a CD38 antibody could improve outcomes without compromising quality of life.

Key results from the CEPHEUS trial demonstrated a significant improvement in minimal residual disease negativity rates, with approximately 60% vs 47% achieving 10^–5 responses when daratumumab was added to the base regimen. The subcutaneous formulation of daratumumab proved particularly beneficial for frail patients, reducing infusion-related adverse effects while maintaining therapeutic efficacy. The trial’s inclusion criteria reflected real-world community populations, including patients with high-risk cytogenetics and multiple comorbidities.

Clinical implications of the CEPHEUS trial suggest that quadruplet therapy can be safely administered to carefully selected transplant-ineligible patients, provided appropriate monitoring and multidisciplinary care support are available. The study reinforces the importance of achieving deep responses in multiple myeloma treatment while balancing functional status considerations. These findings are reshaping treatment paradigms for older myeloma patients, demonstrating that age alone should not preclude intensive therapy when patients can tolerate 4-drug combinations.