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

https://doi.org/10.17650/1818-8346-2020-15-3-38-50

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.

About the Authors

N. V. Skvortsova
Novosibirsk State Medical University, Ministry of Health of Russia
Russian Federation
52 Krasnyy Prospekt, 630091 Novosibirsk, Russia


I. B. Kovynev
Novosibirsk State Medical University, Ministry of Health of Russia
Russian Federation
52 Krasnyy Prospekt, 630091 Novosibirsk, Russia


K. V. Halzov
Novosibirsk State Medical University, Ministry of Health of Russia
Russian Federation
52 Krasnyy Prospekt, 630091 Novosibirsk, Russia


T. I. Pospelova
Novosibirsk State Medical University, Ministry of Health of Russia
Russian Federation
52 Krasnyy Prospekt, 630091 Novosibirsk, Russia


References

1. Rajkumar S.V. Multiple myeloma: 2016 update on diagnosis, risk-stratification, and management. Am J Hematol 2016; 91(7):719–34. DOI: 10.1002/ajh.24402.

2. Kleber M., Ihorst G., Udi J. et al. Prognostic risk factor evaluation in patients with relapsed or refractory multiple myeloma receiving lenalidomide treatment: analysis of renal function by eGFR and of additional comorbidities by comorbidity appraisal. Clin Lymphoma Myeloma Leuk 2012;12(1):38–48. DOI: 10.1016/j.clml.2011.09.216.

3. Kyle R.A., Rajkumar S.V. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia. Macmillan Publishers Limited 2014;28(4):980. DOI: 10.1038/leu.2008.291.

4. Plummer C., Driessen C., Szabo Z., Mateos M.V. Management of cardiovascular risk in patients with multiple myeloma. Blood Cancer 2019:9(3):26. DOI: 10.1038/s41408-019-0183-y.

5. Paiva B., Martinez-Lopez J., Vidriales M.B. et al. Comparison of immunofixation, serum free light chain, and immunophenotyping for response evaluation and prognostication in multiple myeloma. J Clin Oncol 2011;29(12):1627–33. DOI: 10.1200/ JCO.2010.33.1967.

6. Iwama K.I., Chihara D., Tsuda K. et al. Normalization of free light chain kappa/lambda ratio is a robust prognostic indicator of favorable outcome in patients with multiple myeloma. Eur J Haematol 2013;90(2):134–41. DOI: 10.1111/ejh.12050.

7. Kapoor P., Kumar S.K., Dispenzieri A. et al. Importance of achieving stringent complete response after autologous stemcell transplantation in multiple myeloma. J Clin Oncol 2013;31(36):4529–35. DOI: 10.1200/JCO.2013.49.0086.

8. Radocha J., Pour L., Pika T. et al. Multicentered patient-based evidence of the role of free light chain ratio normalization in multiple myeloma disease relapse. Eur J Haematol 2015;96(2):119–27. DOI: 10.1111/ejh.12556.

9. Willrich M.A., Katzmann J.A. Laboratory testing requirements for diagnosis and follow-up of multiple myeloma and related plasma cell dyscrasias. Clin Chem Lab Med 2016;54(6):907–19. DOI: 10.1515/cclm-2015-0580.

10. Dispenzieri A., Kyle R., Merlini G. et al. Myeloma Working Group. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia 2009;23(2):215–24. DOI: 10.1038/leu.2008.307.

11. Dispenzieri A., Kyle R.A., Katzmann J.A. et al. Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma. Blood 2008;111(2):785–9. DOI: 10.1182/blood-2007-08-108357.

12. Rajkumar S.V., Kyle R.A., Therneau T.M. et al. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood 2005;106(3):812–7. DOI: 10.1182/blood-2005-03-1038.

13. Lyubimova N.V., Timofeev Yu.S., Votyakova O.M. et al. Free immunoglobulin light chains in the diagnosis and prognosis of multiple myeloma. Al’manakh klinicheskoy meditsiny = Almanac of Clinical Medicine 2017;45(2):102–8. (In Russ.).

14. Xu Y., Sui W., Deng S. et al. Further stratification of patients with multiple myeloma by International Staging System in combination with ratio of serum free light chains. Leuk Lymphoma 2013;54(1):123–32. DOI: 10.3109/10428194.2012.704033.

15. Garcıa de Veas Silva J.L., Bermudo Guitarte C., Menendez Valladares P. et al. Prognostic value of serum free light chains measurements in multiple myeloma patients. PLoS One 2016;11(11):e0166841. DOI: 10.1371/journal.pone.0166841.

16. Kumar S., Zhang L., Dispenzieri A. et al. Relationship between elevated immunoglobulin free light chain and the presence of IgH translocations in multiple myeloma. Leukemia 2010;24(8):1498–505. DOI: 10.1038/leu.2010.128

17. Jekarl D.W., Min C.K., Kwon A. et al. Impact of genetic abnormalities on the prognoses and clinical parameters of patients with multiple myeloma. Ann Lab Med 2013;33(4):248–54. DOI: 10.3343/alm.2013.33.4.248.

18. Kyrtsonis M.C., Vassilakopoulos T.P., Kafasi N. et al. Prognostic value of serum free light chain ratio at diagnosis in multiple myeloma. Br J Haematol 2007;137(3):240–3. DOI: 10.1111/j.1365-2141.2007.06561.x.

19. Snozek C.L.H., Katzmann J.A., Kyle R.A. et al. Prognostic value of the serum free light chain ratio in newly diagnosed myeloma: proposed incorporation into the international staging system. Leukemia 2008;22(10):1933–7. DOI: 10.1038/leu.2008.171.

20. Van Rhee F., Bolejack V., Hollmig K. et al. High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis. Blood 2007;110(3):827–32. DOI: 10.1182/blood-2007-01-067728.

21. Sthaneshwar P., Nadarajan V., Maniam J.A.S. et al. Serum free light chains: diagnostic and prognostic value in multiple myeloma. Clin Chem Lab Med 2009;47(9):1101–7. DOI: 10.1515/ CCLM.2009.260.

22. Alhaj Moustafa M., Rajkumar S.V., Dispenzieri A. et al. Utility of serum free light chain measurements in multiple myeloma patients not achieving complete response to therapy. Leukemia 2015;29(10): 2033–8. DOI: 10.1038/leu.2015.118.

23. Golenkov A.K., Trifonova E.V., Kataeva E.V. et al. Analysis of free light chains of serum immunoglobulins in evaluating the effectiveness of chemotherapy for multiple myeloma with an intact measurable paraprotein. Gematologiya i transfuziologiy = Hematology and Transfusiology 2019;64(1):7–15. (In Russ.).

24. Votyakova O.M., Lyubimova N.V., Turko T.A. et al. Clinical significance of the study of free light chains of immunoglobulins in multiple myeloma. Vestnik RONTS im. Blokhina RAMN = Bulletin of the N.N. Blokhin Russian Oncology Center Russian Academy of Medical Sciences 2010;21(4):16–21. (In Russ.).

25. Golenkov A.K., Mitina T.A., Lutskaya T.D. et al. Clinical significance of serum immunoglobulin free light chain analysis in multiple myeloma with a different response to chemotherapy. Klinicheskaya onkologiya = Clinical Oncology 2007;6(3):71–5. (In Russ.).

26. Rajkumar S.V., Dimopoulos M.A., Palumbo A. et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014;15:e538–48. DOI: 10.1016/S1470-2045(14)70442-5.

27. Greipp P.R., Miguel J.S., Durie B.G. et al. International staging system for multiple myeloma. J Clin Oncol 2005;23(15):3412–20. DOI: 10.1200/jco.2005.04.242.

28. Durie B.G., Salmon S.E. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, respons to treatment, and survival. Cancer 1975;36(3):842–54. DOI: 10.1002/1097-0142(197509)36:3<842::aid-cncr2820360303>3.0.co;2-u.

29. Mendeleeva L.P., Votyakova O.M., Pokrovskaya O.S. et al. National clinical guidelines for the diagnosis and treatment of multiple myeloma. Gematologiya i transfuziologiy = Hematology and Transfusiology 2016;61(1, Suppl.2):1–24. (In Russ.).


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For citations:


Skvortsova N.V., Kovynev I.B., Halzov K.V., Pospelova T.I. The importance of serum immunoglobulin free light chain assessment for predicting outcome in patients with newly diagnosed multiple myeloma in real clinical practice. Oncohematology. 2020;15(3):38-50. (In Russ.) https://doi.org/10.17650/1818-8346-2020-15-3-38-50

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