Genomic Heterogeneity Affects the Course of MM

• Most patients with MM have multiple distinct subclonal populations as a result of the expansion of genetically different myeloma cells; this causes intratumoral heterogeneity1

• MM is clonally heterogeneous at diagnosis and throughout treament2

• The genomic heterogeneity of MM contributes to treatment resistance and relapse3

• Wide variety of mutations found within a single patient may result in treatment resistance and refractory disease1,3,4

• Furthermore, subclones continually mutate over time, including after treatment, which may contribute to resistance and result in disease progression1,5

Definitions: What is relapsed/refractory disease and a line of therapy?

• Relapsed: recurrence (reappearance of disease) after a response to therapy

• Refractory: progression despite ongoing therapy

• Progression: change in M protein/light chain values

• Line of therapy: change in treatment due to either progression of disease or unmanageable side effects

• Note: initial (or induction) therapy + stem cell transplant + consolidation/ maintenance therapy = 1 line of therapy