Serum free light chain changes offer a more accurate assessment of response to therapy than urine Bence Jones protein excretion measurements in multiple myeloma

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.

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

Blood ◽

10.1182/blood-2009-01-198788 ◽

2009 ◽

Vol 114 (13) ◽

pp. 2617-2618 ◽

Cited By ~ 30

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).

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

Clinical Laboratory ◽

10.7754/clin.lab.2017.171040 ◽

2018 ◽

Vol 64 (04/2018) ◽

Cited By ~ 3

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

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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 ◽

10.1182/blood.v106.11.3479.3479 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3479-3479 ◽

Cited By ~ 1

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 <0.26 were defined as having monoclonal λ FLC and those with ratios >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.

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