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

Abstract

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.

Serological Immunoglobulin-Free Light Chain Profile in Myasthenia Gravis Patients

“…Thanks to their short half-life, and in subjects with normal kidney function, their serum levels can be considered as a direct marker of B cell activity, which is otherwise difficult to measure in routine clinical practice. As a matter of fact, the quantitative assay of κ and λ FLCs and the κ / λ ratio is a useful diagnostic tool in plasma cell dyscrasias, such as mixed cryoglobulinemia, multiple myeloma, monoclonal gammopathy of undetermined significance, and amyloidosis [ 5 – 7 ]. In the last few years, elevated concentrations of polyclonal FLCs in the serum and urine have been reported in patients with rheumatoid arthritis (RA), systemic sclerosis (SS), primary Sjogren syndrome (pSS), and systemic lupus erythematosus (SLE) [ 8 – 11 ].…”

The Role of18F-FDG PET/CT in Multiple Myeloma Staging according to IMPeTUs: Comparison of the Durie–Salmon Plus and Other Staging Systems

“…As a clonal hematologic malignancy, multiple myeloma (MM) is characterized by bone marrow plasma cell infiltration and the presence of serum and urine monoclonal immunoglobulins. The prognosis of MM patients is highly variable; therefore, a reliable staging system is extremely important to optimize appropriate treatment as quickly as possible and avoid irreversible organ damage [ 1 ]. The most widely applied staging systems in MM patients include the International Staging System (ISS) and Durie–Salmon staging system (DSS) [ 2 ].…”

The importance of serum immunoglobulin free light chain assessment for predicting outcome in patients with newly diagnosed multiple myeloma in real clinical practice

“…Таким образом, взаимосвязь концентраций СЛЦκ, СЛЦλ и соотношения СЛЦ κ / λ с известными маркерами, [14,18]. Так, по данным J. L. Garcia de Veas Silva и соавт., значение соотношения СЛЦ κ / λ >47 и концентрации СЛЦκ и СЛЦλ у паци ентов с впервые диагностированной ММ коррелиро вало с наличием почечной недостаточности (уровень креатинина >2 мг / дл; р = 0,023), высокой концент рацией β2микроглобулина (>3,5 мг / л; р <0,001) и Мградиента (>3 г / дл; р = 0,007), плазмоклеточной ин фильт рацией костного мозга >20 % (р <0,001) и нали чием литических поражений костей (р = 0,006), а так же с III стадией по классификации ISS (р < 0,001) [15].…”

“…Содержание СЛЦ в сыворотке крови напрямую отражает их секре цию плазматическими клетками и не зависит от со хранности почечной функции [1,12,13]. По данным ряда исследователей, уровни cекреции СЛЦκ и СЛЦλ и измененное соотношение СЛЦ κ / λ коррелируют с параметрами, отражающими объем опухолевой массы (высокими концентрациями креатинина, β2микро глобулина, Мградиента, инфильтрацией костного мозга плазматическими клетками и III стадией по клас сификации ISS), и являются независимыми предик торами снижения общей выживаемости (ОВ) наряду с β2микроглобулином и стадиями по ISS как у паци ентов, лечившихся традиционными химиопрепарата ми, так и у получавших новые лекарственные агенты, что указывает на возможность их использования для оценки прогноза выживаемости, а также для выяв ления больных с высоким риском прогрессирования [14][15][16][17]. Однако на сегодняшний день остаются неко торые разногласия относительно важности оценки сывороточных СЛЦ, до конца не определены порого вые значения концентрации данных показателей для распределения пациентов в группы с разным исходом заболевания.…”

“…Основные исследования по изучению прогнос тической роли СЛЦ при ММ выполнены в Европе и США [15,16,[18][19][20][21][22]. В России прогностическая значимость СЛЦ у пациентов с ММ недостаточно из учена [13,[23][24][25] ввиду малой доступности определе ния данных показателей пациентам с ММ, что явилось основанием для проведения настоящего исследования.…”