Abstract

Background. The prognosis of patients with multiple myeloma (MM) is significantly different depending on the biological characteristics of the tumor substrate, the microenvironment of the bone marrow, as well as factors associated with the patient’s body. Therefore, the search for new reliable and easily identifiable prognostic markers is relevant for the effective management of patients with this disease.The objective of the study was to assess the prognostic value of the study of serum free light chains (FLC) of immunoglobulins κ and λ and their ratio κ / λ FLC in the blood serum of patients with newly diagnosed MM in real clinical practice.Materials and methods. 369 patients with first diagnosed MM (134 men and 235 women) were examined who were hospitalized in the hematology department of the City Clinical Hospital No. 2 Novosibirsk in the period since January 2012 to December 2017. The median age of the patients was 67 (32–82) years. All patients received induction courses of chemotherapy based on bortezomib. The control group consisted of 56 conditionally healthy individuals: 34 women (60.7 %) and 22 (39.3 %) men with a median age of 62 (40–68) years. The concentration of FLC-κ and FLC-λ (mg / L) in blood serum was determined by immunoturbidimetric method on a Hitachi 911 automated biochemical analyzer using the Freelite Human Lambda and Freelite Human Kappa reagent kits (Binding Site, Great Britain).Results. It was found that in patients with MM, the concentration of serum FLC-κ or FLC-λ was statistically significantly higher compared to the control group and varied depending on the type of MM (p <0.001). The diagnostic sensitivity of the quantitative determination of FLC and their ratio for MM was 98.64 %, compared with 94.04 % in a standard immunochemical study. The values of the ratio κ / λ FLC <0.04 or> 65, as well as the concentration of FLC-κ and FLC-λ are higher than the median obtained in the whole group (FLC-κ ≥702 mg / L and FLC-λ ≥493.2 mg / L), correlate with known factors of poor prognosis for MM (with a high concentration of β2‑microglobulin (>3.5 mg / L) (r = 0.461; p <0.001), plasma cell bone marrow infiltration >60 % (r = 0.420; p <0.001), renal failure (creatinine >177 μmol / L) (r = 0.380; p = 0.002), and also with high lactate dehydrogenase activity (>450 U / L) (r = 0.520; p <0.001) and is associated with poor outcomes. The median overall survival in the group of patients with κ / λ FLC <0.04 or >65 was 49 months compared to 76 months in the group with κ / λ FLC 0.04–65 (log-rank p = 0.012).Conclusion. The determination of free FLC in the blood serum of patients with MM can be used to assess the prognosis of their survival. The value of the κ / λ FLC ratio <0.04 or >65 allows us to divide patients with MM into risk groups with significantly different outcomes and can be used to identify patients at high risk who need more aggressive therapy and more detailed monitoring of the response.

Highlights

  • The prognosis of patients with multiple myeloma (MM) is significantly different depending on the biological characteristics of the tumor substrate, the microenvironment of the bone marrow, as well as factors associated with the patient’s body

  • The objective of the study was to assess the prognostic value of the study of serum free light chains (FLC) of immunoglobulins κ and λ and their ratio κ / λ FLC in the blood serum of patients with newly diagnosed MM in real clinical practice

  • The concentration of FLC-κ and FLC-λ in blood serum was determined by immunoturbidimetric method on a Hitachi 911 automated biochemical analyzer using the Freelite Human Lambda and Freelite Human Kappa reagent kits (Binding Site, Great Britain)

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Summary

Background

The prognosis of patients with multiple myeloma (MM) is significantly different depending on the biological characteristics of the tumor substrate, the microenvironment of the bone marrow, as well as factors associated with the patient’s body. The objective of the study was to assess the prognostic value of the study of serum free light chains (FLC) of immunoglobulins κ and λ and their ratio κ / λ FLC in the blood serum of patients with newly diagnosed MM in real clinical practice. I. The importance of serum immunoglobulin free light chain assessment for predicting outcome in patients with newly diagnosed multiple myeloma in real clinical practice. 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. Харак­ теристика пациентов, включенных в исследование (возраст, пол, тип миеломы, стадия по ISS и Durie–Sal­ mon, концентрации β2‐микроглобулина, креатинина, кальция, альбумина, лактатдегидрогеназы (ЛДГ), ге­ моглобина, степень плазмоклеточной инфильтации костного мозга, наличие мягкотканной плазмоцитомы, проводимая терапия), приведена в табл. Соматический статус по шкале Карновского, %: Somatic status on the Karnowski scale, %:

Мягкотканная плазмоцитома Soft tissue plasmacytoma
IgA multiple
Многофакторный анализ Multivariate analysis
Концентрация вовлеченных
Findings
Мужской пол Male gender
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