Evaluation of Correlation between Serum Free Light-Chain Assay and Bone Marrow Study in Multiple Myeloma Patients
Background: Multiple myeloma is a hematologic malignancy manifested by the secretion of abnormal immunoglobulin. Different methods have been described for diagnosis and patient response to management. Serum free light-chain assay is recently approved in the diagnosis of multiple myeloma patients.
This study aimed to evaluate the diagnostic accuracy of serum free light-chain assay and its agreement to bone marrow findings.
Materials and Methods: Forty-six patients with the diagnosis of multiple myeloma were enrolled in the study. The patients were grouped into newly diagnosed cases (22 patients,47.8%) and known cases who were under treatment (24 patients,52.2%). Bone marrow study was done and percentage and clonal status of plasma cells were evaluated by a combination of immunohistochemistry and flow cytometry. Free light-chain assay was done in all patients and sensitivity, specificity, positive predictive value, and negative predictive value were analyzed.
Results: Thirty of 46 patients showed monoclonal plasma cell infiltration and 16 patients showed polyclonal plasma cell infiltration based on bone marrow findings. An abnormal κ/λ ratio was seen in 15(68.18%) of new cases and 16(66.6%) of known cases. Sensitivity, specificity, PPV and NPV for κ⁄λ ratio were 72.73%, 46.15%, 71%, and 50%, respectively.
Conclusion: In conclusion, due to high false positive and false negative results, the presence of an abnormal serum FLC ratio was not equal to the presence of monoclonal gammopathy, and observation of a normal ratio does not exclude the presence of monoclonal gammopathy.
2.Rafae A, Malik MN, Zar MA, et al. An Overview of Light Chain Multiple Myeloma: Clinical Characteristics and Rarities, Management Strategies, and Disease Monitoring. Cureus. 2018;10(8): e3148.
3. Protein Testing in Patients with Multiple Myeloma: A Review of Clinical Effectiveness and Guidelines [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2015 Jan 9. PMID: 25632494.
4.Sham Z, Yazmin S, Thambiah SC, et al. Light chain multiple myeloma: an evaluation of its biochemical investigations. Malays J Pathol. 2017;39(3):311-315.
5.Willrich MA, Katzmann JA. 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.
6. Aita MHC, Arantes LC, Aita BC, et al. Comparison between immunofixation and electrophoresis for the early detection of relapsed multiple myeloma. J Bras Patol Med Lab. 2015;51(6):359-68.
7. Gertz MA, Greipp PR (Eds). Hematologic malignancies: multiple myeloma and related plasma cell disorders, 1st edn.Springer-Verlag Berlin Heidelberg:Germany,2004.
8. El Naggar AA, El-Naggar M, Mokhamer EH, et al. Prognostic value of serum free light chain in multiple myeloma. Egypt J Immunol. 2015;22(1):69-78.
9. Jenner EL, Evans JAR, Harding SJ. Serum free light chain (FLC) analysis: a guiding light in monoclonal gammopathy management. JALM. 2017;2(1):98-106.
10. Kumar SK, Dispenzieri A, Lacy MQ, et al. Changes in serum-free light chain rather than intact monoclonal immunoglobulin levels predicts outcome following therapy in primary amyloidosis. Am J Hematol. 2011;86(3):251–5.
11.Tosi P, Tomassetti S, Merli A, et al. Serum free light-chain assay for the detection and monitoring of multiple myeloma and related conditions. Ther Adv Hematol. 2013;4(1):37-41.
12.Manzanera GM, Izquierdo JFSM, de Matos AO. Immunophenotyping of plasma cells in multiple myeloma. Methods Mol Med. 2005;113:5-24.
13.Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol . 2016;17(8):e328-e346.
14. Sthaneshwar P, Nadarajan V, Maniam JA, et al. Serum free light chains: diagnostic and prognostic value in multiple myeloma. Clin Chem Lab Med. 2009;47(9):1101-7.
15. Kubicki T, Dytfeld D, Baszczuk A, et al. Clinical usefulness of serum free light chains measurement in patients with multiple myeloma: comparative analysis of two different tests. Postepy Hig Med Dosw (Online) . 2017;71(0):40-46.
16. Nowrousian MR, Brandhorst D, Sammet C, et al. Serum free light chain analysis and urine immunofixation electrophoresis in patients with multiple myeloma. Clin Cancer Res . 2005;11(24 Pt 1):8706-14.
17.Yang Y, Han X, Zheng G, et al. Comparison of two serum freelite chain assay for the diagnosis of primary plasma cell malignant proliferative disease. Health Sci Rep. 2019; 2(4): e113.
18. Tosi P, Tomassetti S, Merli A, et al. Serum freelite chain assay for the detection and monitoring of multiple myeloma and related conditions. Ther Adv Hematol. 2013; 4(1): 37–41.
19. Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538-48.
20. Singh G. Serum Free Light Chain Assay and κ/λ Ratio Performance in Patients without Monoclonal Gammopathies: High False-Positive Rate. Am J Clin Pathol. 2016; 146(2):207-14.
21. Bhole MV, Sadler R, Ramasamy K. Serum-free light-chain assay: clinical utility and limitations. Ann Clin Biochem. 2014;51(Pt 5):528-42.
22.Singh G. Serum free light chain assay and κ/λ ratio: performance in patients with monoclonal gammopathy-high false negative rate for κ/λ ratio. J Clin Med Res . 2017;9(1):46-57.
23.Singhal S, Vickrey E, Krishnamurthy J, et al. The relationship between the serum free light chain assay and serum immunofixation electrophoresis, and the definition of concordant and discordant free light chain ratios. Blood. 2009;114(1):38-9.
24. Jurczyszyn A, Ochrem B. Abnormal serum free light chain ratio does not always indicate monoclonal gammopathy. Pol Arch Med Wewn. 2015;125(7-8):502-4.
25. Bradwell AR, Carr-Smith HD, Mead GP, et al. Serum test for assessment of patients with Bence Jones myeloma. Lancet. 2003;361(9356):489-91.
26. Mead GP, Carr-Smith HD, Drayson MT, et al. Serum free light chains for monitoring multiple myeloma. Br J Haematol. 2004;126(3):348-54.
|Issue||Vol 15 No 3 (2021)|
|Multiple myeloma; Serum free light-chain; Bone marrow|
|Rights and permissions|
|This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.|