Sustained Suppression of Involved Free Light Chain Predicts Long Term Outcomes in Multiple Myeloma after Allogeneic Hematopoietic Stem Cell Transplantation: A Multi-Institutional Study

Background: Allogeneic stem cell transplantation (alloSCT) for multiple myeloma (MM) can offer prolonged remission and may have curative potential. Overproduction of the disease specific clonal serum free light chains by malignant plasma cells (involved free light chain, iFLC) is a marker of disease activity. Underproduction of the uninvolved serum free light chain (uFLC, from non-malignant plasma cells) is a marker of MM mediated immune suppression. Early prediction of relapse after allogeneic SCT remains a challenge, and is important for prognostic and therapeutic purposes. We hypothesized that sustained iFLC suppression at 12 months post-alloSCT would be associated with improved survival.

Methods: The primary cohort was 50 consecutive patients treated with allogeneic SCT from two institutions. This was selected from a total of 60 patients with patients excluded for death (n=6) or relapse (n=4) prior to one year. Data was collected retrospectively 2005-2010 and then prospectively from 2010-2012. Baseline and follow-up serum FLC (at 3 month intervals) were correlated with overall survival (OS). Patients were considered to have a “suppressed” FLC if the serum iFLC was reduced below the uninvolved FLC at 12 months post-alloSCT. OS was measured from 12 months post-alloSCT using Kaplan-Meier plots and the 2 groups were compared using log-rank test. A step-wise backward cox-proportional hazards model was used adjusting for age, CD34⁺ stem cell dose, conditioning regimen (myeloablative vs. reduced intensity), graft versus host disease prior to one year, disease risk by FISH (standard vs. high risk), International Staging System (standard risk vs. high risk) and disease status prior to SCT (complete remission vs. no complete remission).

Results: Median follow-up time was 40.0 months from transplant (12-95.6 months). Longer duration of iFLC suppression was associated with superior outcomes. Patients without sustained iFLC suppression at one year post-SCT had worse OS (p=0.03, Figure 1). The 2-y OS in the sustained iFLC suppression cohort (95% [95% CI 86-NA]) was significantly superior to the non-sustained iFLC suppression cohort (70% [95% CI 57-99]) (P=0.03, Figure 1). By univariate analysis, there were no baseline characteristic differences. By multivariate analysis, lack of iFLC suppression at 1-year post-alloSCT was associated with significantly increased mortality (HR 7.01, 95% CI 1.21-40.8, p=0.03). Patients with iFLC recovery prior to one year had increased relapse risk compared to sustained iFLC suppression (HR 10.4, 95% CI 2.95-36.6, p=0.0003).

Conclusions: Sustained serum iFLC suppression at one year relative to the uFLC is a predictive marker of outcomes following alloSCT for MM. Early recovery of iFLC may be an indicator of disease progression following alloSCT, thus identifying patients who may benefit from preemptive interventions to prevent post-transplant relapse.