Managing Early Relapse in Transplant-Eligible MM and the Influence of Clonal Evolution

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

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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

This segment examines the challenges of early relapse in patients initially presenting with standard-risk multiple myeloma disease and discusses the role of clonal evolution in this context. Early relapse often represents a failure in current risk assessment capabilities at diagnosis, highlighting limitations in traditional fluorescence in situ hybridization (FISH) technologies. The discussion advocates for transitioning to more comprehensive sequencing technologies that can provide detailed genetic information and potentially identify subtle high-risk features missed by conventional testing methods.

Functionally high-risk patients—those without high-risk genetics at diagnosis who relapse within 3 years of transplant—present particularly challenging clinical scenarios requiring departure from standard treatment algorithms. Specific examples include patients with IGL translocations presenting with hyperdiploid genetics that appear favorable but actually confer high-risk characteristics and relative insensitivity to immunomodulatory agents. These subtle genetic features can only be detected through advanced sequencing technologies rather than standard FISH testing.

The management of early-relapse patients extends beyond genetic considerations to include extramedullary disease and circulating plasma cells as important prognostic factors. Despite advances in achieving MRD-negative responses and improved progression-free survival, early relapse patients continue to surprise both patients and physicians. The panel expresses enthusiasm for immunotherapy approaches, including bispecific antibodies, trispecific antibodies, and CAR T-cell therapies, as these novel modalities may effectively target disease that differs from typical myeloma through alternative mechanisms of action.