Performance of Free Light Chain Assays in Clinical Practice.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 757-757 ◽  
Author(s):  
Jerry A. Katzmann ◽  
Angela Dispenzieri ◽  
Roshini S. Abraham ◽  
Robert A. Kyle
Keyword(s):  
Multiple Myeloma ◽  
Clinical Practice ◽  
Light Chain ◽  
Test Performance ◽  
Plasma Cells ◽  
Clinical Laboratory ◽  
Lymphoproliferative Disease ◽  
Free Light Chain ◽  
Al Amyloidosis ◽  
Light Chain Deposition Disease

The quantitative assay for free light chains (FLC) is a recently introduced commercial product (FREELITETM, The Binding Site, Ltd.) that has been reported to be sensitive and specific for detecting and monitoring free light chain diseases such as primary systemic amyloidosis (AL), light chain deposition disease (LCDD), non-secretory multiple myeloma (NSMM), and LCMM (light chain multiple myeloma). We have prospectively evaluated the test performance in clinical practice. Results : In 2003, our Clinical Laboratory received samples for FLC assays from 1020 Mayo Clinic patients. The majority of these patients (88%) had plasma cell disorders (PCD). All 120 patients who did not have PCD had normal K/L FLC ratios. Among these, 52 had non-AL amyloidosis: localized amyloid (23), hereditary (16), senile (6), secondary (3), and amyloid of unknown type (4). The 68 other patients who did not have a PCD were being tested because of peripheral neuropathy, rule out AL, anemia, proteinuria, lymphoproliferative disease, and a number of other indications with small numbers of patients (n=13). Among the monoclonal gammopathy patients were 330 with MM, 269 AL, 115 MGUS, 72 SMM, 22 plasmacytomas, 20 NSMM, 9 macroglobulinemia, 7 LCDD, and a variety of other diagnoses with smaller numbers of patients. The sensitivity of the K/L FLC ratio was 100% in LCDD (7/7) and 70% in NSMM (14/20). The 6 NSMM patients with normal K/L FLC ratios had all been treated with SCT and 5 of the 6 had achieved hematologic remission by bone marrow plasma cells. Among the 110 AL patients who had not been previously treated and who had a FLC assay performed within 120 days of diagnosis, the sensitivity of the K/L FLC ratio was 92% compared to 71% for serum IFE and 84% for urine IFE. Using all 3 assays, there was 99.1% (109/110) sensitivity for detecting monoclonal light chain in AL. Conclusion : The performance of the FLC assay in this prospective analysis matches the results from published retrospective validation studies.

scholarly journals Diagnostic Performance of Quantitative κ and λ Free Light Chain Assays in Clinical Practice

2005 ◽  
Vol 51 (5) ◽  
pp. 878-881 ◽  
Author(s):  
Jerry A Katzmann ◽  
Roshini S Abraham ◽  
Angela Dispenzieri ◽  
John A Lust ◽  
Robert A Kyle
Keyword(s):  
Multiple Myeloma ◽  
Clinical Practice ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Diagnostic Performance ◽  
Clinical Laboratory ◽  
Laboratory Data ◽  
Reference Population ◽  
Clinical Test ◽  
Light Chain Deposition Disease

Abstract Background: The quantitative assay for free light chains (FLCs) is a recently introduced commercial test reported to be sensitive and specific for detecting FLC diseases such as primary systemic amyloidosis (AL), light chain deposition disease (LCDD), nonsecretory multiple myeloma (NSMM), and light chain multiple myeloma. We evaluated its diagnostic performance in clinical practice. Methods: All FLC clinical test results generated in 2003 were abstracted from the Laboratory Information System. Diagnoses were obtained from the Dysproteinemia database and the patient medical history. Results: In 2003, we received samples for FLC assays from 1020 Mayo Clinic patients. The majority of these patients (88%) had bone marrow-derived monoclonal plasma cell disorders (PCDs). The 121 patients who did not have monoclonal gammopathy all had FLC κ/λ ratios within the range of values obtained for a reference population in our laboratory. Among the patients with monoclonal gammopathies were patients with multiple myeloma (330), AL (269), monoclonal gammopathy of undetermined significance (114), smoldering multiple myeloma (72), plasmacytoma (22), NSMM (20), macroglobulinemia (9), LCDD (7), and a variety of other PCDs. Among the 110 AL patients who had not been previously treated and who had a FLC assay performed within 120 days of diagnosis, the FLC κ/λ ratio was positive in 91% compared with 69% for serum immunofixation electrophoresis (IFE) and 83% for urine IFE. The combination of serum IFE and serum FLC assay detected an abnormal result in 99% (109 of 110) of patients with AL. Conclusion: The performance of the FLC assay in this analysis of clinical laboratory data is consistent with results from published retrospective validation studies.

Evaluation of the Concordance of Two Free Light Chains Assays to Identify High Risk Smoldering Myeloma Patients.

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2070-2070 ◽  
Author(s):  
Caroline Moreau ◽  
Emmanuel Rouger ◽  
Basile Henriot ◽  
Martine Escoffre ◽  
Martine Sebillot ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Binding Site ◽  
Light Chain ◽  
Research Funding ◽  
Plasma Cells ◽  
Organ Damage ◽  
Free Light Chain ◽  
Poor Correlation ◽  
Specificity And Sensitivity

Abstract Background Smoldering multiple myeloma (SMM) is a precursor disease of multiple myeloma (MM). According to 2003 classification, the IMWG (International Myeloma Working Group) recommended only to treat patients with end organ damage - often referred as CRAB criteria (hypercalcemia, renal failure, anemia and radiological bone lesions). The standard of care for SMM was to postpone treatment until progression to symptomatic disease occurred. The average annual risk of progression of SMM to MM was 10%/year. In 2014 IMWG proposed a revised classification including 3 new criteria that enable early diagnosis of MM before organ damage. The new criteria of MM needs the presence of more than 10% clonal bone marrow plasma cells combined with either the presence of end organ damage (CRAB criteria) or one of following new biomarkers of malignancy: bone marrow plasma cells ≥60%, serum free light chains (FLC) ratio ≥100 and ≥2 focal lesions on MRI. The FLC criteria were established with Freelite™ assay (The Binding Site Company) and have not been validated with other available assays. Freelite™ assay which used polyclonal antibodies was available since 2001. More recently N Latex assay (Siemens Healthyneers) using monoclonal antibodies has been commercialized in Europe. It is now well know that there is a good correlation between the 2 assays even though results in absolute values are not numerically identical. In this context, the aim of this study was to evaluate the concordance between the two assays to identify high risk SMM, when considering the biomarker of malignancy FLC ratio ≥100. Methods This is a retrospective study including 185 patients with SMM according to 2003 IMWG criteria. FLC concentration and ratio were evaluated in frozen sera with both assays in a BN Prospec and evolution status was collected. Results The average age was 62.5 (± 10.2) years old. Results revealed poor correlation between the 2 assays with a Slope Passing-Bablok value of 0.63 (0.57-0.67) for the FLC κ and of 0.44 (0.35-0.62) for the κ/ λ ratio ≥ 100, and concordance in determining the level of FLC λ with a Slope Passing-Bablok 1.16 (0.99-1.40). A Freelite™ratio ≥ 100 was found in 27 patients (14.3%), and a N Latex ratio ≥ 100 was found in 10 patients (5.3%). All but one patients with an N Latex ratio ≥ 100 had also a Freelite™ ratio ≥ 100. Mean of follow up was 2.4 years. A progression toward MM was observed in 77 (40.7%) patients. Among the 27 patients with Freelite™ ratio ≥ 100, 14 patients (55.5%) have evolved toward MM (figure 1A). Specificity and sensitivity for a Freelite™ ratio ≥ 100 were respectively 88.7% (95% CI 81.8 to 94.0%) and 20.3% (95% CI 11.8 to 31.2%). With the N Latex Assay, only 10 patients had a FLC ratio ≥ 100, in which 7 patients have evolved towards MM. Specificity and sensitivity for a N-Latex ratio ≥ 100 were respectively be 67.0% (95% CI 57.4 to 75.6%) and 53.2% (95% CI 41.5 to 64.7%). Given the poor predictive performance of a N-Latex ratio ≥ 100 we determined that a N-Latex ratio ≥ 70 have adequate specificity of 95.5% (95% CI 89.9 to 98.5%) and a sensitivity of 13.0% (95% CI 6.4 to 22.6%) (figure 1B). 15 patients (8.1%) patients had a N-Latex ratio ≥ 70. Among these, 10 patients (66.6%) have evolved toward MM. Conclusion Our study shows poor correlation between the two FLC assays in SMM patients. A Freelite™ ratio ≥ 100 had a lesser specificity than previously described (specificity 95% in Larsen study [1]). The 100 cut-off value was not performant enough for N-Latex assay. A new ratio is thus needed and was found to be 70 to have sufficient specificity and sensitivity. This result need to be validated in an independent cohort. However, with a Freelite™ ratio ≥ 100 or an N Latex ratio ≥ 70, a significant number of patients would have been overtreated. Physicians should be aware of the limits of both assays. 1.Larsen JT, Kumar SK, Dispenzieri A, Kyle RA, Katzmann JA, Rajkumar SV. Serum free light chain ratio as a biomarker for high-risk smoldering multiple myeloma. Leukemia. 2013;27:941-6. Figure 1 probability of progression to overt multiple myeloma (A) according to Freelite™ ratio (cut-off 100) (B) according to N-Latex ratio (cut-off 70) Figure 1. probability of progression to overt multiple myeloma (A) according to Freelite™ ratio (cut-off 100) (B) according to N-Latex ratio (cut-off 70) Disclosures Moreau: The Binding Site: Other: supply of free light chain assays ; SIEMENS: Other: supply of free light chain assays , Research Funding. Decaux:The Binding Site: Other: supply of free light chain assays , Research Funding; SIEMENS: Honoraria, Other: supply of free light chain assays , Research Funding.

Correlation between serum levels of free light chain and phenotype of plasma cells in bone marrow in primary AL amyloidosis

Amyloid ◽  
2005 ◽  
Vol 12 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Yasuhiro Shimojima ◽  
Masayuki Matsuda ◽  
Takahisa Gono ◽  
Wataru Ishii ◽  
Tomohisa Fushimi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Light Chain ◽  
Plasma Cells ◽  
Serum Levels ◽  
Free Light Chain ◽  
Al Amyloidosis

Serum Free Light Chain Responses Have Greater Concordance with Clinical Outcomes Than Those Assessed By Urine Electrophoresis in Light Chain Multiple Myeloma Patients

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 376-376
Author(s):  
Thomas Dejoie ◽  
Michel Attal ◽  
Philippe Moreau ◽  
Herve Avet-Loiseau
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Research Funding ◽  
Plasma Cells ◽  
Free Light Chain ◽  
Light Chains ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Measurable Disease ◽  
Serum And Urine

Abstract Introduction Guidelines for monitoring light chain multiple myeloma (LCMM) patients currently rely on measurements of the monoclonal protein in urine (Bence Jones proteinuria). However, the presence of light chains in the urine is highly influenced by the individual free light chain, production rate and renal function, which may make accurate monitoring challenging. Serum free light chain measurements are recommended as diagnostic aid for identifying patients with monoclonal gammopathies and as tools to monitor patients with AL amyloidosis and oligo-secretory MM. The correlation between 24hr urine and serum free light chain (sFLC) measurements is insufficient to consider the tests interchangeable, which has prevented recommendations for replacing urine with serum assessment. Here we compare the performance of serum and urine measurements for monitoring 113 newly diagnosed LCMM patients enrolled onto the IFM-2009 trial; and assess the impact of monitoring by either method with clinical outcome. Methods The IFM-2009 trial randomised patients into either arm A (8xRVD) or arm B (3xRVD followed by high-dose Melphalan with autologous stem cell rescue, and 2 further RVD treatments). All patients received one year of Lenalidomide maintenance therapy. Urine protein electrophoresis (UPEP) and immunofixation electrophoresis (uIFE) were performed prospectively using standard laboratory procedures. sFLC concentrations were measured nephellometrically using κ sFLC and λ sFLC Freelite®assays (The Binding Site Group Ltd, UK). Minimal residual disease (MRD) was assessed by 7-color flow cytometry at the end of consolidation therapy. Results At diagnosis, clonal disease was identified in 100% of patients either by an abnormal κ/λ sFLC ratio or by uIFE. However, whilst all patients had measurable disease by the sFLC assay only 64% had measurable disease using UPEP. The discordance in sensitivity was replicated throughout monitoring and monoclonal light chains were quantifiable after cycle 1 and cycle 3 in 71% vs. 37% patients, and 46% vs. 18%, using sFLC vs. 24hr urine measurements, respectively; in keeping with previous reports. To understand the clinical significance of these discordant findings we compared the depth of response determined by sFLC measurement to those determined by urine electrophoresis after 3 cycles of therapy. Patients with quantifiable disease by sFLC or an abnormal κ/λ sFLC ratio had dismal PFS (median PFS: 36 months vs. not reached, p=0.006; 33 months vs. not reached, p<0.0001, respectively). Whereas quantifiable disease by UPEP was uninformative for PFS (36 vs. 47 months, p=0.260), and abnormal vs. normal uIFE only tended towards significance (36 vs. 47 months, p=0.072); suggesting that monitoring with the sFLC assay is more clinically relevant than with 24hr urine after 3 cycles of therapy. Separating the population into patients with negative UPEP at cycle 3 (n=82), patients with a normal sFLC levels had longer PFS than those with abnormal concentrations (not reached vs. 34 months, p=0.015). Concordant with these results, in 78 patients with negative uIFE, an abnormal κ/λ sFLC ratio still heralded a poorer PFS (34 months vs. not reached, p<0.0001) and importantly overall survival (75% OS: 44 months vs. not reached, p=0.016). In contrast, separating the patients into those with identifiable disease by sFLC or an abnormal κ/λ sFLC ratio, the addition of the urine assessment provided no further discriminatory value. The absence of malignant plasma cells in the bone marrow has been proposed as an important end-point for clinical studies, and therefore we assessed the relationship between early monoclonal light chain removal, as determined by serum and urine assessment, and subsequent elimination of malignant plasma cells. Normalisation of κ/λ sFLC ratio after both 1 and 3 treatment cycles had 100% positive predictive value (PPV) for the prediction of MRD negativity post-consolidation, i.e. all patients whose serum FLC ratio normalised during induction went on to achieve MRD negative status post-consolidation; by contrast patients becoming urine IFE negative at cycles 1 and 3 had PPVs of 81% and 78%, respectively. Conclusions Serum FLC measurements offer improved sensitivity and better correlation with clinical outcome than urine assessments, hence providing a strong basis for recommending the former for monitoring LCMM patients. Disclosures Attal: amgen: Consultancy, Research Funding; celgene: Consultancy, Research Funding; janssen: Consultancy, Research Funding; sanofi: Consultancy. Moreau:Amgen: Honoraria; Celgene: Honoraria; Takeda: Honoraria; Janssen: Honoraria; BMS: Honoraria; Novartis: Honoraria. Avet-Loiseau:amgen: Consultancy; celgene: Consultancy; sanofi: Consultancy; janssen: Consultancy.

scholarly journals The Clinical Features of Multiple Myeloma with AL Amyloidosis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 10-10
Author(s):  
Junichiro Nashimoto ◽  
Moe Nomura ◽  
Hirofumi Irita ◽  
Kota Sato ◽  
Kanji Miyazaki ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Features ◽  
Light Chain ◽  
Mayo Clinic ◽  
Plasma Cells ◽  
Staging System ◽  
Stage I ◽  
P Value ◽  
Al Amyloidosis ◽  
Hepatic Amyloidosis

Background Multiple myeloma and AL amyloidosis are both caused by the clonal proliferation of the abnormal plasma cells. Although, the difference of the genetic features of multiple myeloma and AL amyloidosis has been reported, we see some patients present with both cases. We retrospectively investigated the clinical features of patients diagnosed with multiple myeloma and AL amyloidosis. Methods We reviewed medical records of patients who were diagnosed with multiple myeloma and AL amyloidosis before initiating treatment during January 2009 to November 2019 in our institution. We excluded patients who did not reach 10% of the plasma cells in the bone marrow. Patients diagnosed with light chain deposition disease were excluded. Treatment regimens were at the discretion of the treating physician. Results Forty-two patients were diagnosed with multiple myeloma and AL amyloidosis. The median follow-up time since diagnosis was 20 months [0-89]. The median age was 63-year-old [43-85]. There was no difference between the sex (male: female=1:1). Twenty-nine (69.0%) patients had lambda type of light chain. Patients with ISS stage I, II, and III were 13(31.7%), 21(51.2%), and 7(17.1%). Patients with R-ISS stage I, II, and III were 4(10.3%), 30(76.9%), and 5(12.8%). Patients with Revised Mayo Clinic AL amyloidosis Staging System 1, 2, 3, and 4 were 3(10.0%), 4(13.3%), 8(26.7%), and 15(50.0%). Twelve (35.3%), 2 (6.9%), 1 (3.4%) and 1 (4.0%) patients had t(11;14), t(4;14), t(14;16) and del(17p) by FISH analysis, respectively. Fourteen (33.3%), 16(38.1%), and 8(19.0%) patients were diagnosed with cardiac, renal, and hepatic amyloidosis, respectively. Thirty-five (83.3%) patients received Bortezomib containing regimen for the initial treatment (e.g., Bortezomib+Dexamethasone(7.1%), Cyclophosphamide+Bortezomib+Dexamethasone(23.8%), Bortezomib+Melphalan+Dexamethasone(7.1%), Bortezomib+Melphalan+Prednisolone(9.5%), Bortezomib+Lenalidomide+Dexamethasone(35.7%)). Thirteen (31.0%) patients underwent autologous stem cell transplantation with high dose melphalan. Median PFS was 25 months and the median OS was 82 months. There were no significant differences in OS between the I-SSS, R-ISSS, and Revised Mayo Clinic AL amyloidosis Staging System groups. Patients diagnosed with cardiac or hepatic amyloidosis had significantly worse outcome. The median OS diagnosed with and without cardiac amyloidosis were 14 and 28 months (p value = 0.034), and the median OS diagnosed with and without hepatic amyloidosis were 8 and 24 months (p value = 0.012). Conclusion Multiple myeloma with AL amyloidosis, especially cardiac or hepatic amyloidosis, has a poor prognosis even if treated with novel agents. Searching for the optimal treatment for these patient groups remains to be an issue. Disclosures Nashimoto: Janssen: Speakers Bureau; Celgene: Speakers Bureau. Tsukada:Takeda pharmaceutical co: Speakers Bureau. Ishida:Ono pharmaceutical co: Speakers Bureau; Takeda pharmaceutical co: Speakers Bureau; Janssen: Speakers Bureau; Celgene: Speakers Bureau. Suzuki:Bristol-Myers Squibb, Celgene and Amgen: Research Funding; Takeda, Amgen, Janssen and Celgene: Consultancy; Takeda, Celgene, ONO, Amgen, Novartis, Sanofi, Bristol-Myers Squibb, AbbVie and Janssen: Honoraria.

Immunoglobulin Free Light Chain Ratio Is an Independent Risk Factor for Progression of Smoldering Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1487-1487 ◽  
Author(s):  
Angela Dispenzieri ◽  
Robert A. Kyle ◽  
Jerry A. Katzmann ◽  
Dirk Larson ◽  
Joanne Benson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Light Chain ◽  
Plasma Cells ◽  
Free Light Chain ◽  
M Protein ◽  
Baseline Serum ◽  
Smoldering Multiple Myeloma ◽  
Risk Of Progression ◽  
Bone Marrow Plasma

Abstract Background: Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell proliferative disorder with a high risk of progression to symptomatic multiple myeloma. Identification of risk factors that predict progression of SMM to symptomatic MM could identify higher risk patients who might benefit from chemoprevention or more intensive surveillance. We hypothesized that increased monoclonal free kappa or lambda immunoglobulin light chains in smoldering myeloma (SMM), as detected by the serum free light chain (FLC) assay, indicates an increased the risk of progression to active myeloma. Methods: Of 276 pathologically confirmed SMM patients seen at the Mayo Clinic from 1970 to 1995, baseline serum samples obtained within 30 days of diagnosis were available in 273. Results: At a median follow-up of surviving patients of 12.4 years, transformation to active disease has occurred in 161 (59%) patients. An abnormal FLC ratio was present at baseline in 90% of patients. The best break-point for predicting risk of progression was a FLC ratio less than or equal to 0.125 or greater than or equal to 8 (hazard ratio, 2.3; 95% CI, 1.6–3.2) [Figure 1]. The extent of abnormality of FLC ratio was independent of SMM risk categories defined by number of plasma cells in the bone marrow and size of serum M-proteins (bone marrow plasma cells ≥ 10% and serum M protein ≥ 3 g/dL; bone marrow plasma cells ≥ 10% but serum M protein &lt; 3 g/dL; and serum M protein ≥ 3 g/dL but bone marrow plasma cells &lt; 10%). Incorporating the FLC ratio into the risk model, the division of patients into high-, intermediate-, and low-risk groups is 28, 42, and 30% with 5 year progression rates of 76, 51, and 25%, respectively [Figure 2]. Conclusions: The serum immunoglobulin FLC ratio is an important additional determinant of clinical outcome in patients with SMM. Figure Figure Figure Figure

Seeking light-chain amyloidosis very early: The SAVE trial—identifying clonal lambda light chain genes in patients with MGUS or smoldering multiple myeloma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8010-8010 ◽  
Author(s):  
Ping Zhou ◽  
Adin Kugelmass ◽  
Denis Toskic ◽  
Amandeep Godara ◽  
Teresa Fogaren ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Plasma Cells ◽  
Unmet Need ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Rt Pcr ◽  
Smoldering Multiple Myeloma ◽  
Increased Risk ◽  
Germline Genes

8010 Background: In systemic AL amyloidosis (AL), caused by clonal Ig free light chains (LC) produced in 75% of cases by λ clones, patients often present with advanced organ damage, making earlier diagnosis a critical unmet need. Five λ IGLV germline genes account for 75% of AL λ-type ( IGLV 6-57, 1-44, 2-14, 1-51, 3-1) (Blood 2017;129:299), representing 56% of all AL patients. Relative risk of AL versus MM with these clonal genes can be high (7.3, 6-57; 2.5, 1-44), intermediate (1.7, 2-14; 1.2, 1-51) or low (0.8, 3-1) (Amyloid 2009;16:1). Progression to AL from smoldering multiple myeloma (SMM) or monoclonal gammopathy of undetermined significance (MGUS) occurs but is not well appreciated (JCO 2014; 32:2679). SAVE is a trial for λ SMM or λ MGUS patients with a κ:λ FLC ratio < 0.26 and difference between involved and uninvolved FLC > 23mg/L (JCO 2014;32:2699). Methods: Eligible patients ship peripheral blood (PB) or bone marrow (BM) samples to us for RT-PCR with cDNA from CD138+ cells, using primers for the Vλ families (Blood 2001;98:714). Amplicons are sequenced and the IGLV germline genes identified in IMGT (ImMunoGene-Tics, www.imgt.org). If the germline gene is AL-related, further evaluation is pursued. Results: Twenty asymptomatic λ patients from 18 states have been enrolled (3M, 17F) and 23 PB and 4 BM specimens obtained. Medians of months from diagnosis, involved FLC, κ:λ ratios, MNC and CD138-selected cells were 20.5 months, 113mg/L, κ:λ 0.06, 8.1x106 (0.8-24) and 3x105 (0-30), respectively. Seventeen patients have had IGLV genes identified, 12 with the first and 5 with additional specimens including 4 BM. Increased risk of AL was identified in 7 patients, 2 of whom had undiagnosed AL (both with IGLV2-14 germline genes). One patient with SMM diagnosed in 2016 had AL λ-type with GI involvement and is 9 months status post MEL 200 stem cell transplant (SCT), and the second with SMM diagnosed in 2009 had cardiac AL λ-type by heart biopsy with an NT-proBNP 171 (but with a suggestive MRI) and is en route to SCT. Conclusions: The SAVE trial enables early diagnosis of AL λ-type based on the λ IGLV gene used by the clonal plasma cells. By RT-PCR in this pilot study we identified the clonal λ gene 85% of the time. Earlier diagnosis will enable treatment with effective therapy such as MEL 200 SCT. Clinical trial information: NCT02741999.

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).

A Case of Pancoast Syndrome Caused By an Extramedullary Plasmacytoma in Relapsed Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 11-12
Author(s):  
Jiayu Yang ◽  
Aditya Sharma
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Plasma Cells ◽  
Extramedullary Plasmacytoma ◽  
Free Light Chain ◽  
Smoking History ◽  
Kappa Light Chain ◽  
Private Company ◽  
The Right ◽  
Pancoast Syndrome

Extramedullary plasmacytomas are present in 7-18% of multiple myeloma at diagnosis, and up to 13-20% at the time of disease relapse. (Blade J et al., 2011; Varettoni M et al., 2010) A case series in 2010 with 1003 patients found involvement of soft tissues surrounding the axial skeleton in 85% of cases at diagnosis, and 72% of cases at time of relapse. Other sites of involvement included lymph nodes, liver, kidney, airways, skin, breast, and the gastrointestinal tract. (Varettoni M et al., 2010) An extramedullary plasmacytoma leading to Pancoast syndrome has been reported only 3 times in previous literature, in 1979, 1983, and 1984. (Brenner B et al., 1984; Chen KT et al., 1983; Wilson KS et al., 1979) A case of this uncommon presentation is reported here. The patient is a 70-year-old male with a diagnosis of ISS-3 IgG Kappa multiple myeloma (serum monoclonal protein 10 g/L, Kappa light chain 2356.29 mg/L, free light chain ratio 386.28, bone marrow biopsy 61.8% plasma cells) the year prior to the current presentation. He was not a candidate for autologous stem cell transplant due to poor pulmonary function, and hence had a treatment plan for 9 cycles of cyclophosphamide/bortezomib/dexamethasone (CyBorD), of which 6 were completed. Treatment was then stopped due to a macrocytic hypoproliferative anemia thought to be related to early hypoplasia from prior CyBorD. At this time, he was in complete remission with bone marrow biopsy showing 2.8% plasma cells. His medical history was otherwise significant for coronary artery disease with prior myocardial infarction, previous transient ischemic attack with carotid stenosis and carotid endarterectomy, hypertension, dyslipidemia, spinal stenosis with multilevel degenerative changes most pronounced at L3-4, and osteoarthritis. He had a 30 pack-year smoking history, and continued to smoke cigars. The patient presented to hospital 5 months after completion of the above therapy with 2 weeks of right shoulder pain radiating down the arm, and right hand weakness, numbness, and tingling. He had also noted right lower extremity weakness and numbness with some incontinence. The physical exam was significant for right ptosis and myosis (Figure 1), decreased strength and sensation in the right C8-T1 distribution, inability to lift the right lower extremity off the bed, reduced anal sphincter tone, and a post-void residual volume of 700 mL. CT brain and cervical spine showed new abnormal mass-like tissue within the right hemithorax apical region with apparent extension into the cervicothoracic junction. Given his history of multiple myeloma as well as his smoking history, the mass was thought to either be a primary lung malignancy, or an extramedullary plasmacytoma. The patient was therefore admitted for ongoing management and diagnostic work-up. He was seen by the inpatient Hematology service, and noted to have progression of his multiple myeloma with Kappa light chain 885.99 mg/L (free light chain ratio 48.67). He was started on pulse steroids with a plan for daratumumab/lenalidomide/dexamethasone (DRd) with dose reduction of the lenalidomide given his prior history of myelosuppression. Further imaging with MR entire spine showed the right lung apical soft tissue mass extending into the epidural space from C7-T2 with severe spinal cord compression and spinal cord edema (Figure 2), as well as epidural extension of disease at L5 resulting in moderate spinal canal stenosis. The patient was then seen by Radiation Oncology and received 8 Gy as a single fraction to the apical lung mass. Subsequent biopsy of the mass showed a plasma cell neoplasm, Kappa restricted by in-situ hybridization, and compatible with a plasmacytoma. The patient then received two cycles of DRd and thought to be in very good partial response with Kappa light chain 32 mg/L, free light chain ratio 3.8, and resolution of previous apical lung mass and L5 epidural extension on subsequent MR spine. We document here a rare case of plasmacytoma leading to Pancoast syndrome. Given the difference in therapeutic options and prognosis between an extramedullary plasmacytoma and a primary lung malignancy, it is important to recognize this presentation as a diagnostic possibility, and to pursue relevant investigation and targeted management for the same. Disclosures Sharma: Enstasis therapeutics: Current equity holder in private company; Pfizer: Current equity holder in private company; Gilead: Other: shareholder; Contrafect corporation: Current equity holder in private company; Moderna: Other: shareholder.

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