Model of Darwinian evolution in MM assessed by the type of paraprotein secreted: 1 clone is able to produce a complete antibody, whereas the other secretes only a FLC. Chemotherapy is differentially active against the different clones, as different as the impact of other evolutionary bottlenecks such as microenvironment or competition for the stem cell niche. The different selective pressures applied will determine which of the clone(s) will survive and give rise to the relapse. The different clonal composition at relapse will ultimately impact on the different sensitivities to subsequent treatments and therefore on survival. L, light chain only secreting plasma cells; Relapse type 1, relapse characterized by both free light chains and intact immunoglobulin secreting plasma cells; Relapse type 2, relapse characterized only by free light chains secreting plasma cells; Relapse type 3, relapse characterized only by intact immunoglobulin secreting plasma cells; Y, intact immunoglobulin secreting plasma cell.