Early Immunoglobulin Free Light Chain (FLC) Response Post Autologous Peripheral Blood Stem Cell Transplant Predicts for Hematologic Complete Response in Patients with Multiple Myeloma.

Background: FLC is a valuable diagnostic tool to monitor response in patients with AL and oligosecretory MM. It is also prognostic in patients with MGUS. Its value in patients with non-oligosecretory myeloma has not been defined. Because of the short half-life of free-light chains, an early drop in free-light chain might be predictive for long term outcome post PBSCT.

Methods: Between 8/1/03 and 12/10/04, 45 patients with multiple myeloma and abnormal FLC ratios (less than 02.6 or greater 1.65), who were undergoing PBSCT consented to have waste serum from routine post-transplant daily blood draws collected and frozen for future FLC analysis. The immunoglobulin FLC assay (Binding Site, U.K.) was run on samples collected from day +1 until patients were dismissed from our transplant center. Hematologic response was coded according to standard IBMTR criteria at approximately 3 months status post transplant (BJH 1998). Two types of immunoglobulin FLC response were coded: 50% reduction (FLC50) and 90% reduction (FLC90) of the difference of the involved and uninvolved FLC (Leukemia 2006). Two time periods of FLC response were analyzed: early (day 7); and delayed (day 19, range 13 to 24). Endpoints analyzed were overall response (>=PR), complete response rate (CR), progression free survival (PFS), and overall survival (OS).

Results: The median age of the myeloma group was 59 years, and 53% were male. Thirty-three patients were monoclonal kappa, and 12 lambda. Forty-two percent were transplanted in response/plateau, 22% were primary refractory, and 36% relapsed disease. The overall hematologic response rate was 93% with a CR rate of 33%. Twenty-five patients have relapsed at a median of 14.2 months. Twelve patients have died, and median overall survival for the group has not been reached at a median follow-up of 24.6 months. Forty-nine and 58 percent of patients had early and delayed FLC90, respectively. Early FLC90, but not delayed FLC90, predicted for complete response (p<0.001). Neither early nor delayed FLC90 predicted for either PFS or OS. In addition, 89% and 96% of patients had an early and delayed FLC50, respectively. FLC50 at either time point did not predict for overall response, CR, PFS, or OS.

Conclusion: Immunoglobulin free light chain responses are seen within the first weeks post high dose chemotherapy with peripheral blood stem cell transplant. A 90% reduction in FLC seen within the first seven days predicts for complete response. However, this does not yet translate into prolonged PFS or OS, but with longer follow-up separation of the survival curves may be seen.