Key Takeaways From CEPHEUS: Subgroup Analysis

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

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EP: 14.Key Takeaways From CEPHEUS: Subgroup Analysis

The CEPHEUS trial subgroup analysis specifically examined quadruplet versus triplet therapy outcomes in transplant-ineligible multiple myeloma patients, demonstrating approximately 12% improvement in minimal residual disease negativity rates at the 10–5 level. This analysis included high-risk genetic and functionally high-risk patients, showing preserved clinical performance and acceptable safety profiles even in challenging patient populations. The subcutaneous daratumumab formulation proved particularly beneficial for patients with transportation limitations and those requiring manageable adverse effect profiles.

Clinical significance of the CEPHEUS subgroup analysis reinforces the confidence in quadruplet therapy for less fit patients, including those with high-risk genetics or functional limitations. The trial data confirmed that adding CD38 antibody therapy provides meaningful clinical benefit across diverse patient populations while maintaining acceptable toxicity profiles. Safety analyses showed no alarming differences between treatment groups, even when focusing on higher-risk patient subsets.

The CEPHEUS findings support broader implementation of quadruplet therapy in transplant-ineligible patients, with particular emphasis on the value of subcutaneous administration for improving treatment accessibility and patient convenience. The subgroup analysis provides evidence-based support for treating challenging patient populations with intensive regimens when appropriate supportive care is available. These results contribute to the growing body of evidence supporting four-drug combinations as standard of care for appropriate multiple myeloma patients regardless of transplant eligibility.