The Addition of sFLCR Improves ISS Prognostication in Multiple Myeloma (MM).
Authors: Kyrtsonis Marie-Christine , Vassilakopoulos Theodoros P. , Kafasi Nikolitsa , Maltezas Dimitris , Anagnostopoulos Athanasios , Terpos Evangelos , Elefterakis-Papaiakovou Evangelos , Pouli Anastasia , Repousis Panagiotis , Delimpasi Sossana , Anargyrou Konstantinos , Stefanoudaki Catherine , Michalis Eurydiki , Sachanas Sotirios , Tzenou Tatiana , Masouridis Stavroula , Dimou Maria , Angelopoulou Maria K. , Dimopoulou Maria N. , Siakantaris Marina P. , Dimitriadou Evangelia M. , Kokoris Styliani I. , Kalpadakis Christina , Panayiotidis Panayiotis , Dimopoulos Meletios A. , Pangalis Gerassimos A. 
Published: April 2020

Abstract
We have recently shown that serum free light chain ratio (sFLCR) provides independent prognostic information in patients with newly diagnosed MM (Kyrtsonis et al, Br J Haematol, 137: 240–243, 2007). The aim of the present study was to extend our previous observations in a multicenter setting and to investigate the potential additive effect of sFLCR to the ISS system, in determining the prognosis of patients with MM. We analyzed 214 newly diagnosed MM patients (125 kappa-, 89 lambda-). Serum free light chain levels were measured in sera drawn at diagnosis, using a latex-enhanced immunoassay (The Binding Site, Birmingham, UK). Then, the sFLCR was calculated, accordingly as kappa/lambda or lambda/kappa, depending on the monoclonal light chain type of the patient. Based on our previous study “high” sFLCR was defined as ratios ≥3.57 and ≥45.09 for kappa- and lambda- MM respectively. The median age of the patients was 68 years (33–92), 51% were males, 28%, 30%, and 42% had Durie-Salmon stages I, II, and III, 14% creatinine &gt;2 mg/dl, and 13% had Bence-Jones MM. ISS stage was 1, 2, or 3 in 33%, 33%, and 34% of the patients, 48% had CRP ≥4 mg/l, 18% elevated LDH, 31% hemoglobin &lt;10 g/dl, 32% albumin &lt;3.5 g/dl, and 51% bone marrow infiltration ≥50%. The median sFLCR was 6.00 in the 125 kappa-MM, and 46.43 in the 89 lambda-MM patients. With a median follow-up of 16 months (1–105), 88 MM patients with “low” sFLCR had a 3-year disease specific survival (DSS) of 93±4% vs. 63±6% for 126 patients with “high” sFLCR. The corresponding 5-year DSS rates were 83±7% vs. 43±10% (p=0.0001). In multivariate analysis, “high” sFLCR provided prognostic information independent of the value of ISS, as further reflected by the data presented in the table. LDH levels further contributed in the discrimination of prognosis in multivariate analysis: A subgroup of 19 patients (9% of total) with “high” sFLCR plus ISS=3 plus elevated LDH had a 0% projected DSS at 19 months. sFLCR and the previously described models remained predictive of the outcome, if only patients requiring treatment at diagnosis were analyzed. In conclusion, baseline sFLCR appears to be an easily determined, powerful, independent and very promising novel prognostic factor for survival in patients with newly diagnosed MM. Establishment of the optimal cutoff and prospective validation is needed. Its addition to ISS and LDH can identify subgroups of patients with excellent or very poor outcomes.
DSS According to the Combined sFLCR and ISS System Patient Subgroup Pts (#,%) 3-yr DSS (%) 5-yr DSS (%) p “Low” sFLCR and ISS &lt;3 61 (29) 95 90 Either “High” sFLCR or ISS=3 96 (46) 82 56 &lt;0.0001 “High” sFLCR and ISS=3 50 (24) 37 24