Advancing First-Line Therapy for Multiple Myeloma: Updates From IsKia and IMROZ Trials

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

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

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EP: 16.Advancing First-Line Therapy for Multiple Myeloma: Updates From IsKia and IMROZ Trials

The IsKia clinical trial demonstrated approximately 10% improvement in minimal residual disease (MRD) negativity rates when added to carfilzomib, lenalidomide, and dexamethasone, with consistent benefits observed at both the 10^–5 and 10^–6 levels. The trial included high-risk patients and those with double-hit genetics, showing ability to narrow the response gap between standard-risk and high-risk populations. Treatment abandonment rates remained similar between groups, indicating acceptable tolerability profiles for the quadruplet regimen.

International Myeloma Society risk stratification is evolving to better identify truly high-risk patients who require different treatment approaches. The refined definition focuses on patients with translocation plus additional abnormalities in 1q or 1p, and those with deletion 17p, representing approximately 15% to 20% of patients rather than the broader 40% previously classified as high risk. This more precise risk stratification aims to identify patients where current standard treatments are inadequate.

The ADMIRAL trial analysis of 1q21 patients demonstrated that approximately 40% of multiple myeloma patients have this abnormality, with clear benefit from isatuximab addition throughout their treatment journey. Patients with 1q abnormalities showed longer progression-free survival, better overall response rates, and increased MRD negativity when receiving continuous anti-CD38 therapy. These findings support the general principle that 4-drug combinations provide superior outcomes compared to 3-drug regimens across most patient populations.