Serum free Light Chains Profile as Early Biomarker with Predictive Value after autologous Transplant in Multiple Myeloma

Background: Serum free light chain Freelite® assays, is a quantitative method to measure serum free light chain (FLC) concentration, and could be a simple and accurately indicator to predict the early relapse in Multiple Myeloma(MM) patients with apparently complete response. FLC are small proteins that cross easily through the glomeruli pores, entering the proximal tubule, where they are reabsorbed and metabolised. In patients with a low tumour burden, the amount of FLC produced can remain below this reabsorption capacity and so have no detectable in urine. However, serum levels of FLC continue to rise and therefore become a good biomarker to detect an early progression.

Aims of study: To determine the predictive value of serum FLC concentration in MM patients in complete response after autologous stem cell transplant as a early biomarker of relapse.

Patients and Methods: Observational, analytical study performed in 24 MM patients included in an autologous stem cell transplant program during 2002–2006 in one center. All patients received induction therapy with VBCMP/VBAD (×4), follow by G-CSF movilization and collection of CD34+ cells. The infussion of CD34+(mean: 5.39×10⁶/kg; range: 2.24–18.8) was performed after conditioning with high doses of Melphalan. Serum samples were collected on 0, +4, +7, +21, +30, +60 y +90 days and stored frozen at −80°C. Serum FLC were analysed in a nephelometer system following the manufacturer instructions. We have compare the increase of FLC according M-component subtype, number of CD34+ cells administered, time until immune reconstitution, administration of coadyuvant AM3-glycopeptical therapy, infections in early postrasplant period, maintenance therapy and time free relapsed survival. Descriptive statistical analysis, ANOVA comparative test and Kaplan-Meier survival study was performed.

Results: 24 patients, 47.0 % females, mean age 63.2 y (38–72), IgG (46.1%), IgA (15.4%), light chains (23.0%), non secretory (7.7%), time to immune reconstitution 15–17 days, kappa/lambda ratio at baseline 57.0 (CI95% 0.8,20.3), days: +4:37.3(CI95% 0.1,3.2), +7:1.85(CI95% 1,3), +21:2.37 (CI95% 0.4,2.0), +30:0.87 (CI95% 0.2,0.9), +60:0.4 (0.2, 2.1) and +90:1.26 (CI95% 0.3, 2.9). Mean relapsed free survival 27.6 m (CI95% 9,55), OS 59.0 m (CI95% 27,76), 7 patients have dead for progression. At day +21 opposite correlation kappa/lambda ratio and RFS was observed.

Comments: The early increase of free serum kappa/lambda chains ratio could be an useful biomarker to predict RFS and OS in MM patients in complete response after therapy.