Aberrant Immunoglobulin Variations as Indicators of Eventual Clonal Changes in Symptomatic Multiple Myeloma Patients' Course

We studied aberrant changes (A-IgC) in the production of monoclonal intact immunoglobulin (M-Ig) or serum free light chains (sFLC) during symptomatic MM patients’ relapse and we evaluated their frequency and the associated disease characteristics. Patients and Methods: 234 symptomatic MM patients, with available follow-up M-Ig and sFLC measurements, were retrospectively studied. Light chain escape (LCE) was defined as sFLC increase with stable or falling M-Ig, M-Ig escape (MCE) as decreasing sFLC with increasing M-Ig, de-differentiation (DD) as clinical relapse with normal or decreased MIg and sFLC and Clonal Domination (CD) as normalization of formerly increased IgG, IgA or FLC in relapsing patients presenting increase of another monoclonal component. Results: A-IgC was observed in 18% of patients, LCE in 8%, MCE in 3%, DD in 2% and CD in 5%; The median time from diagnosis to A-IgC was 48.5, 35.5, 31 and 46 months for LCE, MCE, DD and CD respectively. Median survival from A-IgC to last follow-up or death was 2.6, 3.3 and 6.3 months respectively for LCE, MCE and DD versus 31.1 months for CD patients (p=0.0002). Patients received a median of 3 treatment lines, including novel agents and/or ASCT, prior to A-IgC. In conclusion, LCE, MCE and DD are late events in the course of MM, observed in heavily pre-treated patients, associated with a very aggressive disease with shortened survival thereafter, probably due to the emergence of new resistant clones or to the dominance of pre-existing minor ones.