|Table of Contents|

The role of kappa/lambda light chain ratio in evaluating the efficacy of bortezomib in the treatment of patients with multiple myeloma

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2025 02
Page:
255-262
Research Field:
Publishing date:

Info

Title:
The role of kappa/lambda light chain ratio in evaluating the efficacy of bortezomib in the treatment of patients with multiple myeloma
Author(s):
YANG Juanjuan; LI Xiaotong; DAI Suya
Department of Clinical Laboratory,Zhengzhou Central Hospital Affiliated to Zhengzhou University,Henan Zhengzhou 450001,China.
Keywords:
multiple myeloma; serum free light chain; ratio of serum free light chain; bortezomib; therapeutic effect
PACS:
R733.3
DOI:
10.3969/j.issn.1672-4992.2025.02.013
Abstract:
Objective:To investigate the role of kappa/lambda light chain ratio in evaluating the efficacy of bortezomib in the treatment of patients with multiple myeloma (MM).Methods:150 patients with MM of our hospital from February 2020 to May 2023 were selected as subjects,who were treated with bortezomib chemotherapy.The clinical and genetic factors that may affect the efficacy of bortezomib chemotherapy in patients with MM were collected.The curative effects of the two groups after 3 courses of treatment were evaluated,and the patients were divided into two groups:Remission group (partial remission+near complete remission+complete remission) and non-remission group (stable disease+disease progression).The levels of serum free light chain （sFLC）(including κ light chain and λ light chain) in the two groups before treatment and after each course of treatment were detected,and the level of ratio of serum free light chain （rFLC） was calculated （rFLC=κ/λ）.rFLC levels were stratified to analyze the factors affecting the therapeutic effect of bortezomib in MM patients.The dynamic changes of rFLC levels in two groups of MM patients were analyzed and compared by the method of repeated measurement variance.Joint model was used to analyze the relationship between rFLC level and the efficacy of MM patients treated with bortezomib.Longitudinal fluctuation linear mixed effects (LME) model and Cox survival sub-model were constructed,and the two models were combined by correlation coefficient.A restricted cubic spline Logistic regression model was established to analyze the dose-response relationship between rFLC levels and the efficacy of bortezomib in patients with MM.Results:The time effect,intergroup effect and interaction effect of rFLC level between the two groups were statistically significant (P＜0.001).The level of rFLC in both groups decreased significantly after treatment,compared with pre-treatment (P＜0.001).Multivariate variance analysis result showed that the levels of rFLC in the first,second and third course of treatment in the non-remission group were higher than those in the remission group (P＜0.001).The results of Joint model analysis showed that the risk of poor prognosis increased by 5% for every 0.1 increase in rFLC level (P＜0.01).Through the stratified analysis of other factors affecting the curative effect on the level of rFLC,it was found that R-ISS stage and bone marrow plasma cells had a significant positive effect on rFLC level before treatment (P＜0.05).The restricted cubic spline analysis result showed,there was a significant positive correlation between the level of rFLC and the probability of non-remission of bortezomib,especially when the level of rFLC was 0.89,the probability of non-remission of bortezomib increased significantly with the increase of its level.Conclusion:Bortezomib can effectively improve serum levels of sFLC-κ,sFLC-λ and rFLC in MM patients.rFLC level was closely related to the therapeutic effect of bortezomib.R-ISS stage and bone marrow plasma cells had significant positive effects on rFLC level.

References:

［1］ MAURA F,BERGSAGEL PL.Molecular pathogenesis of multiple myeloma:clinical implications［J］.Hematol Oncol Clin North Am,2024,38(2):267-279.
[2] CHEN Q,ZHANG M,ZHENG S,et al.Therapeutic progress in relapsed/refractory multiple myeloma［J］.Ann Hematol,2024,103(6):1833-1841.
[3] TAO J,SRINIVASAN V,YI X,et al.Bone-targeted bortezomib inhibits bortezomib-resistant multiple myeloma in mice by providing higher levels of bortezomib in bone［J］.J Bone Miner Res,2022,37(4):629-642.
[4] SINGH G.Serum and urine protein electrophoresis and serum-free light chain assays in the diagnosis and monitoring of monoclonal gammopathies［J］.J Appl Lab Med,2020,5(6):1358-1371.
[5] BENKERT P,MEIER S,SCHAEDELIN S,et al.Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis:a retrospective modelling and validation study［J］.Lancet Neurol,2022,21(3):246-257.
[6] MEIER S,WILLEMSE EAJ,SCHAEDELIN S,et al.Serum glial fibrillary acidic protein compared with neurofilament light chain as a biomarker for disease progression in multiple sclerosis［J］.JAMA Neurol,2023,80(3):287-297.
[7] 中国医师协会血液科医师分会,中华医学会血液学分会,黄晓军.中国多发性骨髓瘤诊治指南（2022年修订）［J］.中华内科杂志,2022,61(5):480-487. Chinese Medical Doctor Association Hematology Physician Branch,Chinese Society of Hematology,HUANG XJ.Chinese guidelines for diagnosis and treatment of multiple myeloma (revised in 2022) ［J］.Chinese Journal of Internal Medicine,2022,61(5):480-487.
[8] NERVO A,RAGNI A,RETTA F,et al.Bone metastases from differentiated thyroid carcinoma:current knowledge and open issues［J］.J Endocrinol Invest,2021,44(3):403-419.
[9] YAMAMOTO S,EGASHIRA N.Pathological mechanisms of bortezomib-induced peripheral neuropathy［J］.Int J Mol Sci,2021,22(2):e888.
[10] ROZENOVA K,WILLRICH M,SNYDER M,et al.Kappa free light chain drift prompts the need for a new upper limit of normal free light chain ratio to avoid an epidemic of kappa light chain monoclonal gammopathy of indermined significance［J］.J Appl Lab Med,2023,8(4):742-750.
[11] LEE S,LEE SY,KIM S,et al.Differentiating multiple myeloma and osteolytic bone metastases on contrast-enhanced computed tomography scans:the feasibility of radiomics analysis［J］.Diagnostics (Basel),2023,13(4):e755.
[12] TSENG YD.Radiation therapy for painful bone metastases:fractionation,recalcification,and symptom control［J］.Semin Radiat Oncol,2023,33(2):139-147.
[13] LONG T,HU S.18F-FDG PET/CT in clear cell sarcoma with multiple bone metastases［J］.Clin Nucl Med,2022,47(6):566-568.
[14] TAWIAH R,BONDELL H.Multilevel joint frailty model for hierarchically clustered binary and survival data［J］.Stat Med,2023,42(21):3745-3763.
[15] GULLA A,MORELLI E,SAMUR MK,et al.Bortezomib induces anti-multiple myeloma immune response mediated by cGAS/STING pathway activation［J］.Blood Cancer Discov,2021,2(5):468-483.
[16] SINGH G,WHITAKER BM,WU AHB,et al.Serum free light chain quantification testing:comparison of two methods for disease monitoring［J］.J Appl Lab Med,2022,7(6):1290-1301.
[17] DE NOVELLIS D,FONTANA R,CAROBENE A,et al.Serum free light-chain ratio at diagnosis is associated with early renal damage in multiple myeloma:a case series real-world study［J］.Biomedicines,2022,10(7):e1657.
[18] LONG TE,INDRIDASON OS,PALSSON R,et al.Defining new reference intervals for serum free light chains in individuals with chronic kidney disease:results of the istopmm study［J］.Blood Cancer J,2022,12(9):e133.
[19] KISHIDA T.Editorial comment on a case of mediastinal teratoma with malignant transformation into angiosarcoma and relapse with multiple bone metastases that was cured by multidisciplinary treatment［J］.IJU Case Rep,2022,6(2):e96.

Memo

Memo:
-
Last Update: 1900-01-01