Serum free light chains and multiple myeloma: Is it time to extend their application?

Markovic, Uroš; Leotta, Valerio; Tibullo, Daniele; Giubbolini, Rachele; Romano, Alessandra; Fabro, Vittorio Del; Parrinello, Nunziatina Laura; Cannizzaro, Maria Teresa; Raimondo, Francesco Di; Conticello, Concetta

doi:10.1002/ccr3.2636

Cited by 5 publications

(4 citation statements)

References 25 publications

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“…FLC ratio can be normal, especially in pre-myeloma stages with low risk of progression, in younger patients, or in those subjects with concomitant increased of uninvolved light-chain levels [ 45 , 46 , 47 ]; however, this condition is not frequent in active MM, as reported in our case series (only 18% of patients, mostly with concomitant increased of uninvolved FLC), also in accordance with previously published studies [ 47 , 48 ]. Conversely, FCL ratio is abnormal in almost all non-secretory myeloma with a sensitivity close to 100% [ 16 , 17 , 18 , 19 ]. In our case series, we confirmed the high diagnostic potential of sFLC ratio for light-chain MM identification, and we also showed that the standardized values were highly correlated with renal failure, especially in light-chain MM.…”

Section: Discussionmentioning

confidence: 99%

“…Free kappa or lambda chain hyperproduction is an indirect index of clonal plasma cell expansion and proliferation [ 13 ]; therefore, serum FLC ratio is an optimal minimally invasive biomarker of the differential diagnosis of benign and malignant plasma cell disorders [ 14 , 15 ]. Indeed, sFLC is a breakthrough biomarker of MM with a sensitivity close to 100% for non-secretory myeloma, as its FLC ratio is always abnormal, even in the absence of M-protein, thus rendering this marker an optimal tool for monitoring oligo- or non-secretory plasma cell disorders [ 16 , 17 , 18 , 19 ]. Moreover, sFLC is used for screening together with protein electrophoresis, immunofixation, and 24 h urine studies [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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Serum Free Light-Chain Ratio at Diagnosis Is Associated with Early Renal Damage in Multiple Myeloma: A Case Series Real-World Study

et al. 2022

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The serum free light-chain (FLC) ratio is a sensitive tool for the differential diagnosis of plasma cell disorders and is biomarker of multiple myeloma (MM) progression from premalignant conditions. Here, we investigate the potential role of FLC ratio at diagnosis in identifying early renal damage in MM patients and other correlations with clinical, laboratory, and molecular findings. A total of 34 MM patients who had undergone autologous stem cell transplantation were included in this retrospective case series study, and FLC quantification was performed with nephelometric assays. In our study, sFLC ratio was significantly associated with light-chain MM and β-2 microglobulin levels, likely indicating a high disease burden at diagnosis, especially in patients without heavy chain M-protein at serum electrophoresis. Moreover, the sFLC ratio was inversely correlated with glomerular filtration rate, possibly identifying early renal damage in MM patients. Our preliminary results confirm the importance of early sFLC evaluation, especially in patients with the light-chain MM type and low disease burden, to minimize the risk of late renal failure.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Serum Free Light-Chain Ratio at Diagnosis Is Associated with Early Renal Damage in Multiple Myeloma: A Case Series Real-World Study

et al. 2022

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“…According to IMWG, biochemical relapse should be treated in high-risk patients—i.e., those with aggressive disease at diagnosis or relapse or adverse cytogenetics and short treatment-free interval, or with a suboptimal response—in order to avoid severe symptomatic disease [ 19 , 20 ]. In a previous work, our group has already suggested extending the application of sFLC to first and subsequent relapse, since it had an anticipatory role in clinical relapse, including cases of aggressive non-secretory or oligo-secretory EMD disease [ 21 ]. This suggestion comes from four clinical cases in which sFLC evaluation preceded clinical aggressive relapse.…”

Section: Discussionmentioning

confidence: 99%

Role of Serum Free Light Chain Assay in Relapsed/Refractory Multiple Myeloma. A Real-Life Unicentric Retrospective Study

Markovic

Romano

Bellofiore

et al. 2021

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Background: In the era of novel drugs a growing number of multiple myeloma (MM) patients are treated until disease progression. Serum free light chain (sFLC) assay is recommended for disease monitoring in oligo-secretory and micromolecular MM. Methods: In this real-life survey, a total of 130 relapsed/refractory MM patients treated at our center with at least three lines were investigated as a retrospective cohort. Results: The median age at diagnosis was 64 years and more than half of patients were male. A total of 24 patients (18%) had oligo-secretory/micromolecular disease at diagnosis. More than 20% of 106 normo-secretory patients had oligo-secretory/micromolecular escape. In order to evaluate potential role of sFLC assay before (“pre”) and after (“post”) every treatment line, involved serum free light chain values (iFLC) less than 138 mg/mL and serum free light chain ratios (FLCr) <25 were identified by using ROC curve analysis. The analysis of the entire cohort throughout four treatment lines demonstrated a statistically significant negative impact on progression-free survival (PFS) for both involved pre-sFLC and its ratio (respectively p = 0.0086 and p = 0.0065). Furthermore, both post-iFLC and post-FLCr greater than the pre-established values had a negative impact on PFS of the study cohort; respectively, p = 0.014 and p = 0.0079. Odds ratio analysis evidenced that patients with both involved post-sFLC greater than 138 mg/mL and post-FLCr above 25 at disease relapse had a higher probability of having clinical relapse (respectively p = 0.026 and p = 0.006). Conclusions: Alterations of sFLC values, namely iFLC and FLCr, both prior to treatment initiation and in the course of therapy at every treatment line, could be of aid in relapse evaluation and treatment outcome. We therefore suggest close periodical monitoring of sFLC assay, independently from secretory status.

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“…Shift from negative to positive urine immune-fixation and Bence Jones proteinuria are predictor markers of progression to active MM. 30 , 32 , 33 Dynamic monitoring of sFLC 34 and M component are helpful to identify evolving SMM type, 35 with an emerging prognostic role. 36 Based on the pioneering work of Dr. Dispenzieri and colleagues who evaluated disease progression in 273 SMM patients at Mayo Clinics, an involved/uninvolved FLC ratio of ≥8 is a significant risk factor for progression, 37 and if sFLC ratio rises to ≥ 100, the 2 year risk of progression approaches 80%, thus to be considered a myelomadefining event in the IMWG guidelines.…”

Section: Initial Diagnostic Work-upmentioning

confidence: 99%

How We Manage Smoldering Multiple Myeloma

et al. 2020

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Smoldering myeloma (SMM) is an asymptomatic stage characterized by bone marrow plasma cells infiltration between 10-60% in absence of myeloma-defining events and organ damage. Until the revision of criteria of MM to require treatment, two main prognostic models, not overlapping each other, were proposed and used differently in Europe and in US. Novel manageable drugs, like lenalidomide and monoclonal antibodies, with high efficacy and limited toxicity, improvement in imaging and prognostication, challenge physicians to offer early treatment to high-risk SMM. Taking advantage from the debates offered by SOHO Italy, in this review we will update the evidence and consequent clinical practices in US and Europe to offer readers a uniform view of clinical approach at diagnosis, follow-up and supportive care in the SMM setting.

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Serum free light chains and multiple myeloma: Is it time to extend their application?

Abstract: In nonsecretory, oligo‐secretory, and light chain multiple myeloma patients, serial sFLC evaluation could precede biochemical and clinical disease progression, even in extramedullary relapse, thus initiating early treatment with novel anti‐MM agents.

Cited by 5 publications

References 25 publications

Serum Free Light-Chain Ratio at Diagnosis Is Associated with Early Renal Damage in Multiple Myeloma: A Case Series Real-World Study

Serum Free Light-Chain Ratio at Diagnosis Is Associated with Early Renal Damage in Multiple Myeloma: A Case Series Real-World Study

Role of Serum Free Light Chain Assay in Relapsed/Refractory Multiple Myeloma. A Real-Life Unicentric Retrospective Study

How We Manage Smoldering Multiple Myeloma

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