Multiple myeloma is characterized by recurrent relapses6

While outcomes have improved with the recent availability of targeted agents and combination therapies, most patients with multiple myeloma (MM) inevitably relapse.11,12 With each subsequent line of therapy, the duration and quality of response deteriorates, and the risk of another relapse increases.11,13,14

Overall response rates decrease with subsequent lines of treatment4

Overall response rate with subsequent relapse in multiple myeloma

A Heterogeneic Disease

At the time of diagnosis, the cellular and genetic architecture of multiple myeloma is highly complex and heterogeneous across patients.9,15 Within each patient clonal diversity continuously evolves throughout the treatment continuum.9 Somatic mutations, chromosomal translocations and deletions, and epigenetic modifications accumulate over time within myeloma clones as the disease advances. This evolution may occur through branching pathways, where mutations create different clones that may drive disease evolution and treatment resistance.7 Genetic heterogeneity of these myeloma cells highlight the need for simultaneously targeting multiple mechanisms of disease, including protein degradation.16,17

Myeloma cell heterogeneity can evolve over time9

MGUS, monoclonal gammopathy of undetermined significance; MM, multiple myeloma

Multiple myeloma is heterogenous across patients, with many patients harboring anywhere from three to seven detectable subclones concurrently.9,18 Within each patient, clonal diversity continuously evolves throughout the treatment continuum,9. The emergence of new dominant subclones gives rise to disease progression and resistance.7,16,19