Prognostic Value of Serum Free Light Chains Measurements in Multiple Myeloma Patients

The outcome for patients with Multiple Myeloma (MM) is highly variable, therefore, the existence of robust and easy to determine prognostic markers is extremely important for an efficient management of these patients. Presently, there is a debate about the role of the serum free light chains (sFLC) in the prognosis of MM patients both at diagnosis and after treatment. The aim of this study is to evaluate in a cohort of newly diagnosed MM patients from the Southern area of Spain, the prognostic value of sFLC both at baseline and after treatment.

180 patients with a median age of 69 years were followed-up for a median time of 35 (18-61) months. The sFLC ratio (sFLCR) was calculated using the monoclonal sFLC as numerator. Patients were divided in two groups according to a sFLCR cut-off based on ROC analysis. The primary endpoints were the Overall Survival (OS) and the Progression-free Survival (PFS). Additionally, thirty-six MM patients treated with novel agents (Bortezomib/Dexamethasone) that achieved Complete Response (CR) or stringent CR (sCR) before autologous stem cell transplantation were studied to assess the impact of sCR in Disease Free Survival (DFS) and OS.

During follow-up there were 72 disease-related deaths. The 5-years OS for the whole group was 51%. However, separate analysis of patients with sFLCR above (group "high") or below (groups "low") the cut-off value of 47 shows an OS of 23% and 73%, respectively (HR = 5.03, 95%CI 2.99-8.50, p<0.001). In addition, analysis by ISS stage, showed that the presence of high sFLCR was always significantly associated with a worse OS. Multivariate analysis identified sFLCR (HR = 4.42, 95%CI 2.57-7.60, p<0.001) and beta-2-microglobulin (B2M) (HR = 3.04, 95%IC 1.75-5.31, p<0.001) as independent risk factors for adverse outcome. A new risk stratification model based on sFLCR≥47 and B2M>3.5 mg/L provided a statistically more significant result for this cohort when compared with the conventional ISS system. The HR for the new model were 2.84 (95% CI, 1.39-5.79, p = 0.004) for patients in stage 2 and 15.39 (95% CI, 6.35-37.33, p<0.001) for those in stage 3. Finally, in the group of patients reaching CR (19/36) or sCR (17/36) after induction, the median DFS for CR patients was 29 months, and NR for sCR patients (HR = 3.73; 95% CI 1.15-12.13, p = 0.03). Importantly, achieving sCR also translated into a significantly longer OS (5y-OS: sCR-89% versus CR-49%; p = 0.003; OS: sCR-NR versus CR-52 months).

Our findings confirm the observations that the sFLCR has a major role in the survival of MM patients. A cut-off of sFLCR≥47 was shown to have an independent prognostic value at diagnosis, and a proposed "New Staging System" allows an accurate and simple method to risk stratify MM patients. Furthermore, because achievement of sCR was shown to represent a response state deeper than conventional CR resulting in greater OS and DFS, our study supports the continuity of sFLC ratio as part of the response criteria for MM patients.