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

Opinion
Video

Panelists discuss how early relapse in standard-risk patients represents a failure of current risk assessment methods and may require advanced sequencing technologies to identify hidden high-risk features that traditional fluorescence in situ hybridization testing misses.

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.

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