BackgroundThe 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.Materials and Methods180 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.ResultsDuring 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).ConclusionsOur 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.

ObjectivesTo evaluate the Bio-Rad D-100®, an HPLC analyzer for glycated hemoglobin (HbA1c) determination, and to compare its performance with the Menarini HA-8180V® and Sysmex G8®.MethodsMethod comparison was performed according to Clinical and Laboratory Standards Institute (CLSI) EP9-A2 guidelines. We selected 100 samples from the routine laboratory workload and analyzed them in duplicate with the three analyzers. The imprecision study was performed according to CLSI EP5-A2 guidelines for both inter-assay and intra-assay variability. Bias was assessed with external quality control material. To establish linearity, CLSI EP6-A protocol was followed.ResultsMethod comparison (95% confidence intervals in parentheses): D-100 vs G8: Passing-Bablok regression; y=0.973(0.963–0.983)×−0.07(−0.07−0.069); r=0.9989. Bland-Altman mean difference: −0.229%HbA1c (−0.256: −0.202); Relative bias plot: D-100/G8 vs D100-G8 mean ratio=0.971(0.967−0.975). D-100 vs HA-8180V: Passing-Bablok regression; y=0.944(0.932–0.958)×−0.078(0.024−0.173); r=0.9989. Bland-Altman mean difference: −0.363%HbA1c (−0.401: −0.325); Relative bias plot D-100/HA-8180V vs D100-HA-8180V mean ratio=0.955(0.952−0.958). Inter-assay coefficient of variation (CV): 0.81%. Intra-assay CV: 1.04% (low level), and 0.78% (high level). Bias against target value=2.332%. Linearity: r2=0.998 in the concentration range 4.4−13.9%HbA1c. Carry-over: 0.0024%.ConclusionsThe Bio-Rad D-100 shows good correlation with G8 and HA-8180V. There is a small proportional systematic difference (2.7% and 5.6%, respectively) in both comparisons. Inter and intra-assay CVs are both lower than the lowest CV obtained in studies performed with D-100 and other instruments.

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Multiple Myeloma (MM) is a malignancy of B cells characterized by an atypical proliferation of plasma cells. IgD MM has a very low incidence (2% of total MM cases) and it´s characterized by an aggressive course and a worse prognosis than other subtypes. The serum free light chains (sFLC) are very important markers for monitoring patients with MM and other monoclonal gammopathies. When the sFLC are present in low concentrations, it is often difficult to detect them by conventional methods such as serum protein electrophoresis and serum immunofixation. This case is a good example of the utility of sFLC in the monitoring of treatment and relapse of patients with MM. The sFLC determinations detected when chemotherapy applied was not being completely effective and it predicted a relapse before new clinical findings were present. We report the rare case of a patient diagnosed of IgD MM with associated light chain kappa Primary (AL) Amyloidosis and characterized by clinical findings of very bad prognosis (high levels of sFLC kappa at diagnosis, high renal impairment and subsequent development of intracranial plasmacytoma), aggressive course and refractory to several lines of treatment.