Suppression of Involved Immunoglobulin Free Light Chain Post Therapy and Survival Outcomes Following Autologous Stem Cell Transplantation for Myeloma

Background:  Depth of response to therapy in multiple myeloma can be predictive of long term clinical outcomes.  Various studies across the spectrum of myeloma patients have indicated the prognostic significance of attaining a complete remission (CR).  Normalization of serum free light chains (FLC) may add to the sensitivity of assessing disease response.  Anecdotally, we have noted that patients in whom the clonal or involved FLC not only normalizes but actually suppresses below the uninvolved FLC seem to have superior outcomes.  We studied whether this depth of FLC suppression was predictive of clinical outcomes in our post-transplant cohort.    

Methods:  Records from 697 patients who underwent an autologous stem cell transplant (ASCT) at our institution from 1/2001-12/2011 were reviewed.   All post-transplant serum FLC values were reviewed.  Patients were considered to have a “suppressed” FLC if the clonal or involved FLC reduced below the value of the uninvolved FLC within 12 months of their transplant.  Duration of suppression was assessed based on follow up serum FLC measurements.  Time to progression (TTP) and overall survival (OS) based on depth of FLC suppression were calculated using Kaplan-Meir analysis.

Results:  All patients were treated with high dose melphalan followed by an ASCT.  Median age at the time of ASCT was 60 years (range 35-76) with median time from diagnosis to ASCT of 7 months (range 2-196 months).  With a median follow up time of 5.9 years, 385 (55%) were alive at time of analysis and 463 (66%) had relapsed.  Median TTP for the entire cohort was 26 months (95% CI; 24-30 months).  246 patients had at least one time when their involved FLC suppressed below the uninvolved FLC after ASCT.  The median TTP was 36 months for patients with a suppressed FLC compared with 19 months (p<0.0001) for the rest. Median OS was 6.5 years vs. 4.7 years for those in whom the involved FLC did and did not suppress once respectively (p=0.0013).  Duration of FLC suppression was significantly associated with superior outcomes.  For those patients whose FLC remained suppressed on at least three consecutive occasions, median TTP was not reached compared with 21 months (p<0.0001).  Similarly, median OS was superior for patients with sustained FLC suppression; median OS not reached vs. 4.9 years for unsuppressed patients (p<0.0001, figure 1).  These observed improvements in clinical outcomes were independent of attainment of a CR.

Conclusions:  Suppression of the involved FLC below the uninvolved FLC is associated with superior TTP and OS in myeloma patients treated with an ASCT.  Beyond the level of suppression, the duration of suppression is also highly associated with superior outcomes independent of attaining a complete response.  Depth of treatment response to ASCT when measured by sustained FLC suppression can identify patients who will experience long term disease control.