scholarly journals Day 21 serum Free Light Chain (FLC) levels as a predictor of response to therapy in symptomatic multiple myeloma

2021 ◽  
Vol 3 (1) ◽  
pp. 110-118
Author(s):  
Sabina Langer ◽  
◽  
Lakshmi Mythilli Mulam ◽  
Keyword(s):  
Multiple Myeloma ◽  
Induction Chemotherapy ◽  
Light Chain ◽  
Curve Analysis ◽  
Free Light Chain ◽  
Response To Therapy ◽  
Newly Diagnosed ◽  
Roc Curve Analysis ◽  
Serum Free Light Chain ◽  
Good Partial Response

Introduction: Serum Free Light Chain (sFLC) assay has a major role in the screening, diagnosis and monitoring in patients with Multiple Myeloma (MM). Measuring involved Free Light Chain (iFLC) has a proven advantage due to the short half-life compared to that of M-protein, thus useful as a prognostic tool for the assessment of response to therapy. It is established that achieving VGPR (very good partial response) or better after induction chemotherapy is associated with better OS (overall survival) and PFS (progression free survival) in myeloma patients. Few studies have shown that early reduction in iFLC during treatment is associated with achievement of VGPR or better. Objective: To study the predictive value of reduction of involved free light chain level on Day 21 of chemotherapy for achievement of VGPR after 4 cycles of induction chemotherapy. Methods: We conducted a prospective observational study in twenty eight patients of newly diagnosed Multiple Myeloma with iFLC ≥ 100mg/L. Serum FLC assay was done at baseline and on day 21 of therapy. All patients were followed up till the end of induction therapy for response assessment based on the IMWG criteria. Receiver Operator Characteristic (ROC) curve analysis was done to determine the cut off value of percent reduction in day 21 iFLC for achievement of VGPR or better. Results: After the induction chemotherapy, out of 28 patients, 13 patients achieved CR, 8 patients achieved VGPR, 4 patients achieved PR and 2 patients had stable disease (≥ VGPR = 21 patients, < VGPR = 6 patients). One patient expired after 2nd cycle of chemotherapy. The mean per cent reduction in day 21 iFLC level as compared to baseline was 91.5% and 57.1% in patients achieving ≥ VGPR and < VGPR (P < 0.0001), respectively. No other baseline parameter was found to be significantly different between the 2 groups. ROC curve analysis demonstrated a cut off of 84% reduction in iFLC value on day 21 (AUC of 0.937) had a sensitivity of 85.7% and a specificity of 100% in predicting the achievement of VGPR after four cycles of induction chemotherapy. Conclusion: Monitoring iFLC levels on Day 21 can be used as an important tool for early identification of responders/non responders to myeloma therapy. We recommend serum FLC assay to be done on day 21 as a real time assessment of treatment response in newly diagnosed myeloma patients. Key words- Multiple Myeloma, involved Free Light Chain (iFLC), Very Good Partial Response (VGPR)

Serum Free Light Chain Predict Overall Survival and Response to Therapy in Patients with Newly Diagnosed Multiple Myeloma

2018 ◽  
Vol 64 (04/2018) ◽  
Author(s):  
Yanis Meddour ◽  
Momahed Rahali ◽  
Salah Belakehal ◽  
Fatma Ardjoun ◽  
Samia Chaib ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Light Chain ◽  
Free Light Chain ◽  
Response To Therapy ◽  
Newly Diagnosed ◽  
Serum Free ◽  
Serum Free Light Chain

Use of the Serum Free Light Chain Assay in Assessment of Response to Therapy in Multiple Myeloma: Validation of Recently Proposed Response Criteria in a Prospective Clinical Trial of Lenalidomide Plus Dexamethasone for Newly Diagnosed Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3479-3479 ◽  
Author(s):  
Shaji Kumar ◽  
Morie A. Gertz ◽  
Suzanne R. Hayman ◽  
Martha Q. Lacy ◽  
Angela Dispenzieri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Free Light Chain ◽  
Response To Therapy ◽  
Response Criteria ◽  
Primary Amyloidosis ◽  
Newly Diagnosed ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
The Difference

Abstract Background: The serum free light chain (FLC) assay is increasingly used to monitor patients (pts) with oligo-secretory or non-secretory multiple myeloma (MM) and pts with primary amyloidosis lacking measurable monoclonal protein in the serum or urine. Criteria to use this assay to assess response to therapy have recently been proposed (Rajkumar SV, Kyle RA. Best Pr Clin Haematol2005;18:585–601) but have not been validated. The goal of this study was to validate the response criteria for the FLC assay in a prospective trial of lenalidomide plus dexamethasone in newly diagnosed MM. Methods: 34 pts were enrolled in the trial; 27 pts who had serial FLC assessments were studied. FLC estimation was carried out using the serum FLC assay (FreeliteH, The Binding Site Limited, UK) performed on a Dade-Behring Nephelometer. Pts with κ /λ FLC ratio &lt;0.26 were defined as having monoclonal λ FLC and those with ratios &gt;1.65 as having a monoclonal κ FLC. The monoclonal light chain isotype was considered the “involved” FLC isotype, and the opposite light chain type as the “uninvolved” FLC type. Partial response (PR) required an abnormal baseline FLC ratio and any one of the two following criteria: 1) a 50% decrease in the level of the involved FLC plus a 50% decrease (or normalization) in the ratio of involved/uninvolved FLC or 2) 50% decrease in the difference between involved and uninvolved FLC levels. Complete response (CR) required normalization of FLC ratio and negative serum and urine immunofixation. Response at 4 months or earlier by the Bladé criteria was compared to FLC response criteria from the same evaluation. Results: Three pts had normal FLC levels and ratio and were not included in the analysis. 23 of the remaining 24 achieved a PR or better by Bladé criteria. A 50% decrease in the level of the involved FLC plus a 50% decrease (or normalization) in the ratio of involved/uninvolved FLC correctly classified 20 of the 22 responding pts (sensitivity 91%); 2 pts could not be evaluated since baseline FLC ratio could not be calculated. On the other hand, a 50% decrease in the mathematical difference between involved and uninvolved FLC levels correctly classified all 24 responding pts (sensitivity 100%). The one non-responding pt by Blade criteria was correctly classified by both FLC criteria. All pts were correctly classified by both criteria when only those with a baseline “involved” FLC level of at least ≥10mg/dL (≥100mg/L) were considered (15 pts). Conclusions: This study demonstrates that the serum FLC assay can be used to assess response to therapy. A 50% decrease in the difference between “involved” and “uninvolved” FLC levels will suffice as FLC criteria for PR, eliminating the need for the alternative criteria based on the involved FLC level and the ratio. We recommend that this FLC response criteria be used only in pts not having measurable levels of serum and /or urine M protein.The FLC response criteria will now enable most patients with oligo-secretory and non-secretory MM to enter trials for which they are currently ineligible due to “lack of measurable serum or urine M protein.” This study is limited by the lack of adequate non-responders to calculate specificity and lack pts who progressed to validate progression criteria and needs further validation.

scholarly journals 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 ◽  
Vol 110 (3) ◽  
pp. 827-832 ◽  
Author(s):  
Frits van Rhee ◽  
Vanessa Bolejack ◽  
Klaus Hollmig ◽  
Mauricio Pineda-Roman ◽  
Elias Anaissie ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Prognostic Significance ◽  
Complete Response ◽  
High Serum ◽  
Free Light Chain ◽  
Response To Therapy ◽  
Rapid Reduction ◽  
Serum Free ◽  
Serum Free Light Chain

Abstract Serum-free light chain (SFLC) levels are useful for diagnosing nonsecretory myeloma and monitoring response in light-chain–only disease, especially in the presence of renal failure. As part of a tandem autotransplantation trial for newly diagnosed multiple myeloma, SFLC levels were measured at baseline, within 7 days of starting the first cycle, and before both the second induction cycle and the first transplantation. SFLC baseline levels higher than 75 mg/dL (top tertile) identified 33% of 301 patients with higher near-complete response rate (n-CR) to induction therapy (37% vs 20%, P = .002) yet inferior 24-month overall survival (OS: 76% vs 91%, P < .001) and event-free survival (EFS: 73% vs 90%, P < .001), retaining independent prognostic significance for both EFS (HR = 2.40, P = .008) and OS (HR = 2.43, P = .016). Baseline SFLC higher than 75 mg/dL was associated with light-chain–only secretion (P < .001), creatinine level 176.8 μM (2 mg/dL) or higher (P < .001), beta-2-microglobulin 297.5 nM/L (3.5 mg/L) or higher (P < .001), lactate dehydrogenase 190 U/L or higher (P < .001), and bone marrow plasmacytosis higher than 30% (P = .003). Additional independent adverse implications were conferred by top-tertile SFLC reductions before cycle 2 (OS: HR = 2.97, P = .003; EFS: HR = 2.56, P = .003) and before transplantation (OS: HR = 3.31, P = .001; EFS: HR = 2.65, P = .003). Unlike baseline and follow-up analyses of serum and urine M-proteins, high SFLC levels at baseline—reflecting more aggressive disease—and steeper reductions after therapy identified patients with inferior survival.

scholarly journals The importance of bone marrow examination in determining complete response to therapy in patients with multiple myeloma

Blood ◽  
2009 ◽  
Vol 114 (13) ◽  
pp. 2617-2618 ◽  
Author(s):  
Cheng E. Chee ◽  
Shaji Kumar ◽  
Dirk R. Larson ◽  
Robert A. Kyle ◽  
Angela Dispenzieri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Light Chain ◽  
Plasma Cells ◽  
Complete Response ◽  
Free Light Chain ◽  
Response To Therapy ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Serum And Urine

Abstract The current definition of complete response in multiple myeloma includes a requirement for a bone marrow (BM) examination showing less than 5% plasma cells in addition to negative serum and urine immunofixation. There have been suggestions to eliminate the need for BM examinations when defining complete response. We evaluated 92 patients with multiple myeloma who achieved negative immunofixation in the serum and urine after therapy and found that 14% had BM plasma cells more than or equal to 5%. Adding a requirement for normalization of the serum-free light chain ratio to negative immunofixation studies did not negate the need for BM studies; 10% with a normal serum-free light chain ratio had BM plasma cells more than or equal to 5%. We also found that, on achieving immunofixation-negative status, patients with less than 5% plasma cells in the BM had improved overall survival compared with those with 5% or more BM plasma cells (6.2 years vs 2.3 years, respectively; P = .01).

scholarly journals Evaluating Prognostic Value of Patients with Newly Diagnosed Multiple Myeloma By Serum Free Light Chain κ/λ Ratio in Combination with LDH

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5623-5623
Author(s):  
Chengcheng Fu ◽  
Panfeng Wang ◽  
Feiran Gong ◽  
Jiazi Zhou ◽  
Ying Yao ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Insufficiency ◽  
Light Chain ◽  
Poor Prognosis ◽  
Progression Free Survival ◽  
Free Light Chain ◽  
Newly Diagnosed ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
The Difference

Abstract Objective The data were analyzed for the roles of the measurement of serum free light chain (sFLC) and LDH in the prognosis of newly diagnosed multiple myeloma(NDMM) patients. Methods The clinical data was retrospectively analyzed for 96 newly diagnosed multiple myeloma(NDMM) patients at hematology department of the first affiliated hospital of Soochow's University from September 28,2012 to December 30,2105. The levels of serum free light chain and LDH were measured and the κ/λ ratios were calculated, so we could analyze the roles of sFLC and LDH in the prognosis of newly diagnosed multiple myeloma (NDMM) patients. Results Among the patients withλlight-chain MM, theλlight-chain levels showed a significant positive correlation with serum creatinine, β2-mg and numbers of bone marrow plasma cells and it was negatively associated with levels of serum total protein. At the same time, the patients with k light-chain MM, the k light-chain levels was not showed statistically correlation with those levels above. The morbidity of renal insufficiency in theλlight-chain MM groups was 25.5%(13/51), it was 6.7%(3/45) in the k light-chain MM groups. The morbidity of renal insufficiency was more higher in theλlight-chain MM groups(P=0.009). The follow-up duration ranged from 5.0~59.3 months (mean 19 months). The median progression-free survival (PFS) was 15.1 months for the high free light chain ratio group(sFLCR≥100 or ≤0.01) and 29.1 months for the low free light chain ratio group (0.01) sFLCR<100<, respectively. And the difference was statistically significant (P<0.001).The mean of overall survival(OS) between the high free light chain ratio group and the low free light chain ratio group was 45.9 monthes and 47.5 monthes, respectively. And the difference was statistically significant (P=0.0047). Log-rank univariate analysis showed that elevated LDH levels and obvious abnormally sFLCR were independent prognostic factors of MM patients. Cox multi-factor analysis discovered that the LDH levels was the only poor-prognosis factor. The sFLCR (≥100 or ≤0.01) and LDH≧225U/L could serve as two risk factors. The patients who had one or more risk factor had poor prognosis than the patients who had none of them. The median progression-free survival(PFS) between the two groups were 15.1 months versus 29.1 months,respectively(P=0.001).The mean of overall survival(OS) between the two groups were 44.5 months versus 49.4 months, respectively(P=0.01). And the difference was statistically significant. Conclusions The λ light-chain can more easily lead to the renal insufficiency than the k light-chain. The patients with λ light-chain MM have higher morbidity of renal insufficiency than the patients with k light-chain MM. The baseline LDH levels is the poor-prognosis factor for MM patients. We recommend combine the serum free light chain ratio with the LDH levels to evaluate the prognosis of MM patients. The patients who have either the sFLCR (≥100 or ≤0.01) or LDH≧225U/L at the time of diagnosis have poor prognosis than the patients who have none of them. Disclosures No relevant conflicts of interest to declare.

scholarly journals Utility of serum free light chain measurements in multiple myeloma patients not achieving complete response to therapy

Leukemia ◽  
2015 ◽  
Vol 29 (10) ◽  
pp. 2033-2038 ◽  
Author(s):  
M Alhaj Moustafa ◽  
S V Rajkumar ◽  
A Dispenzieri ◽  
M A Gertz ◽  
M Q Lacy ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Complete Response ◽  
Free Light Chain ◽  
Response To Therapy ◽  
Serum Free ◽  
Serum Free Light Chain
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