An Intact Immunoglobulin IgAλ Multiple Myeloma Patient Exhibiting Light Chain Escape

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5008-5008
Author(s):  
Maria Kraj ◽  
Barbara Kruk ◽  
Krzysztof Warzocha ◽  
Andrzej Szczepinski ◽  
Kelly Endean ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bone Marrow Biopsy ◽  
Light Chain ◽  
Plasma Cells ◽  
Induction Treatment ◽  
Mild Renal Impairment ◽  
Multiple Myeloma Patient ◽  
Monoclonal Protein ◽  
Serum And Urine

Abstract Abstract 5008 A 48 year old man was referred to the Institute of Hematology and Transfusion Medicine, Warsaw, Poland in April 2008 with anemia (Hemoglobin; 10. 4 g/dl) and mild renal impairment (eGFR; 75. 4 mL/min/1. 73m2). An initial diagnostic monoclonal protein screen (serum protein electrophoresis (SPE), serum immunofixation electrophoresis (IFE) and serum free light chain (FLC) analysis) revealed an IgAλ monoclonal protein (0. 8g/dL) with monoclonal serum FLC and an abnormal serum FLC κ/λ ratio (0. 0001; RI, 0. 26–1. 65). A bone marrow biopsy at that time confirmed 60% involvement of monoclonal λ - restricted plasma cells; a bone survey did not detect any osteolysis. The patient was diagnosed with multiple myeloma (MM) (ISS stage I, Durie and Salmon stage IA) and was initially treated with 6 cycles of vincristin, doxorubicin and dexamethasone (VAD). The patient responded well to the induction treatment and subsequently underwent a successful autologous stem cell transplantation (ASCT). The patient was monitored for 3 years subsequent to the ASCT with both serum and urine electrophoresis, serum FLC analysis (Freelite) and heavy chain/light chain (HLC) immunoassays (Hevylite). Sixteen months following the ASCT the dFLC (involved λ FLC– uninvolved κ FLC) concentration began to increase, the FLC κ/λ ratio became abnormal with a trace of λ Bence Jones protein (BJP) detected by urine IFE. However, both SPE and IFE were normal and the HLC ratio (IgAλ/IgAκ) was within the normal range. During the next 9 months the dFLC continued to increase and a λ BJP could now be clearly detected on the urine IFE. 27 months following the ASCT the patient sustained a pathological fracture of the tibiae and was referred to our centre 4 months later. At this point, the dFLC concentration was highly elevated (3168 mg/L) with a λ BJP detectable by both serum and urine IFE. However, there was no detectable monoclonal intact immunoglobulin by serum IFE or HLC analysis, indicating disease relapse by a separate FLC clone; referred to as light chain escape (LCE). A bone marrow biopsy revealed 15% involvement of λ restricted plasma cells; this time a bone survey identified osteolysis. The patient was diagnosed with progression of multiple myeloma and received 6 cycles of bortezomib, cyclophosphamide and dexamethasone (VCD regimen). He responded well to treatment and 3 years following the ASCT achieved a CR as indicated by a normalized κ/λ FLC ratio, negative immunofixation with 1–3% bone marrow plasma cells. The patient is now well and able to continue with normal life. In this case study the increase in the dFLC levels was the first indication of disease progression and highlights the importance of monitoring intact immunoglobulin MM patients with serum FLC immunoassays for early detection of LCE. Disclosures: Endean: The Binding Site Group Ltd: Employment. Harding:Binding Site: Employment.

scholarly journals Successful Treatment of Concurrently Diagnosed Multiple Myeloma and Myelodysplastic Syndrome with Isolated Del(5q) with Lenalidomide, Bortezomib, and Dexamethasone

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 17-18
Author(s):  
Nyomi Washington ◽  
Eugen A Shippey ◽  
Michael B Osswald
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Partial Response ◽  
Myelodysplastic Syndrome ◽  
Bone Marrow Biopsy ◽  
Induction Therapy ◽  
Successful Treatment ◽  
Light Chain ◽  
Plasma Cells ◽  
Bone Marrow Blasts

Lenalidomide is known to be an effective therapy for multiple myeloma (MM) and for myelodysplastic syndrome with isolated del(5q). However, there have been very few reports of treatment of both conditions using lenalidomide when they are diagnosed concurrently. A review of the literature revealed two reports of MM and del(5q) MDS treated with lenalidomide. We report the case of a patient simultaneously diagnosed with multiple myeloma and myelodysplastic syndrome with isolated del(5q) who was treated successfully with lenalidomide. The patient is a 74 year old female who was referred to hematology for worsening chronic macrocytic anemia with a hemoglobin of 9.4 g/dL. A serum protein electrophoresis (SPEP) was obtained during her workup and demonstrated an IgG kappa monoclonal spike of 4.7 g/dL. Free light chain analysis demonstrated a kappa/lambda ratio of 36.7. The patient was mildly hypercalcemic at 10.6 g/dL but had no renal insufficiency. Platelet and white blood cell counts were normal. There were no osteolytic lesions on skeletal survey and a whole body PET scan identified no bony disease or plasmacytomas. A β-2 microglobulin level was 3.7 mg/L and albumin was 3.3 g/dL. Bone marrow biopsy revealed 60% plasma cells in a 70% cellular marrow. Granulocytic and megakaryocytic dysplasia was identified. Fluorescence in situ hybridization returned showing a 4:14 translocation in 72% of analyzed nuclei and monosomy 13 in 61% of nuclei analyzed consistent with an unfavorable risk profile. Chromosome analysis also revealed a 5q deletion in 15 of 20 analyzed cells. Bone marrow blasts were measured at 1%. Therefore, the patient concurrently met diagnostic criteria for stage II IgG kappa multiple myeloma per the International Staging System and low risk myelodysplastic syndrome with isolated del(5q) per the 2016 WHO classification of MDS with a Revised International Prognostic Scoring System Score (IPSS-R) of 2. She was started on lenalidomide 25 mg daily, bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 and dexamethasone 20 mg on days 1, 8, and 15 of a 21 day cycle. After 3 cycles of therapy, serum immunofixation electrophoresis showed an unquantifiably low IgG kappa monoclonal spike and the patient's kappa/gamma light chain ratio had normalized to 1.1. Hemoglobin and calcium returned to normal. On repeat bone marrow biopsy, there was normocellular marrow with 4% polytypic plasma cells by kappa/lambda immunohistochemistry. No dysplasia was identified and bone marrow blasts were 1.5%. Therefore, the patient achieved a very good partial response (VGPR) to therapy for multiple myeloma according to International Myeloma Working Group criteria within 3 months. She met National Comprehensive Cancer Network criteria for response of her MDS to lenalidomide by normalization of hemoglobin. The patient's case demonstrates successful treatment of concurrently diagnosed multiple myeloma and MDS with isolated del(5q) using lenalidomide. Among the two other similar cases we discovered in the literature, one patient was treated with low-dose lenalidomide and dexamethasone [Nolte, et al. Eur J Haematol. 2017 Mar;98(3):302-310.], and the other patient was treated with high-dose lenalidomide and dexamethasone, achieving a partial response [Ortega, et al. Leuk Res. 2013 Oct;37(10):1248-50.]. Neither patient received a proteasome inhibitor. In our case, the patient was treated with higher intensity induction therapy for multiple myeloma and achieved a VGPR. She did not have worsening cytopenias during therapy, and in fact experienced normalization of her blood counts. Therefore, it is reasonable to treat patients simultaneously diagnosed with MM and MDS with isolated del(5q) with standard three-drug induction therapy for multiple myeloma. While our approach makes sense in the abstract, hematology/oncologists should be aware that it works in practice. Disclosures No relevant conflicts of interest to declare.

Bone Marrow Biopsy May Be Required During the Initial Evaluation of Individuals with Asymptomatic Monoclonal Gammopathy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5067-5067
Author(s):  
Meletios Athanasios Dimopoulos ◽  
Evangelos Terpos ◽  
Maria Gkotzamanidou ◽  
Evangelos Eleutherakis-Papaiakovou ◽  
Magdalini Migkou ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Biopsy ◽  
Plasma Cell ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Incidental Finding ◽  
M Protein ◽  
Monoclonal Protein

Abstract Abstract 5067 The incidental finding of a monoclonal gammopathy during workup for various conditions or in the context of a routine check-up is increasingly common. Several “patients” are then referred for diagnostic evaluation of their monoclonal gammopathy and additional workup is needed. It has been proposed that a bone marrow (BM) aspirate and biopsy is indicated when the monoclonal protein (M-protein) is ≥1.5 g/dL, when abnormalities are noted in the complete blood cell count, serum creatinine level, serum calcium level, or radiographic bone survey, in individuals with non-IgG monoclonal gammopathy and in those with an abnormal serum free light chain (FLC) ratio. The aim of this study was to identify factors that could aid in the evaluation of individuals presenting with asymptomatic monoclonal gammopathy and in whom invasive diagnostic testing with a bone marrow biopsy is considered. Thus, we analyzed our database and identified patients who were referred to the Department of Clinical Therapeutics of the University of Athens, Greece, for evaluation of asymptomatic monoclonal gammopathy and in whom a BM trephine biopsy, a serum and urine protein electrophoresis (SPEP) with immunofixation and quantitative immunoglobulins were performed. SPEPs were scanned and M-protein was measured using imaging analysis software. Patients with a monoclonal M-protein ≥ 3 g/dl (30 g/L), i.e. those diagnosed with asymptomatic/smoldering myeloma (SMM) or Waldenstrom's macorglobulinemia based on the standard criteria, were not included in the analysis. Clonality of BM plasma cells or lymphoplasmacytes was assessed by immunohistochemistry. Patients who eventually were diagnosed with plasma cell related conditions (i.e. amyloidosis, peripheral neuropathy, dermatoses, etc.) were also excluded from the analysis. Our analysis included 161 patients: 53% were females, median age was 64 year (range 33–89 years), 53% had a monoclonal IgG protein, 15.5% had a monoclonal IgA protein, 24% a monoclonal IgM protein and 2.5% had only a monoclonal light chain, while 4% had a biclonal protein. In 64% of patients the monoclonal light chain was kappa and in 37% was lambda. The median serum M-protein was 0.948 g/dl (range 0.1–2.99 g/dl); 52% of patients had an M-protein of <1 g/dl and 79% of <2 g/dl. Immunoparesis of at least one of the uninvolved immunoglobulins was present in 38% of cases and of both of the uninvolved immunoglobulins in 6%. Median BM infiltration by monoclonal plasma cells or lymphoplasmacytes was 15%. In 66.5% of individuals there was a BM infiltration of ≥10% by monoclonal plasma cells or lymphoplasmacytes, while in 10% of the studied cases the BM infiltration was ≥50%. A significant correlation of the size of M-protein and of the infiltration of the BM was found (R=0.592, p<0.001). However, 27% of patients with M-protein <0.5 g/dl had ≥10% clonal plasma cells or lymphoplasmacytes in their BM biopsies. The respective rates were 46% for those with M-protein <1 g/dl, 54% for those with M-protein 1.5 g/dl and 58% for those with M-protein <2 g/dl. Ninety per cent of those who had immunoparesis of at least one of the uninvolved immunoglobulins had ≥10% clonal plasma cells or lymphoplasmacytes. A BM infiltration of ≥10% was more frequent in individuals with a monoclonal IgG or IgA protein (72% and 80%, respectively) vs. 45% of those with a monoclonal IgM protein (p=0.015). Light chain isotype, age and gender were not predictive of the degree of BM plasma cell infiltration. In multivariate analysis, immunoparesis of at least one of the uninvolved immunoglobulins (OR: 6.45, 95% CI: 2.32–18, p<0.001), an IgG or IgA monoclonal protein (OR: 2.67, 95% CI: 1.1–6.4, p=0.028) and an M-protein of ≥1 g/dl (OR: 5.4, 95% CI: 2.23–13) were independently associated with the presence of ≥10% of clonal infiltration in BM biopsy. By combining the above risk factors we found that in those who had all three, 97% had ≥10% clonal cells in the BM biopsy, while in those with 0–1 of the above factors the probability to find ≥10% clonal cells was 43%. These findings indicate that even patients with low risk for BM infiltration by clonal plasma cells, may be diagnosed as SMM when a BM biopsy is performed. In conclusion, our data on a large number of individuals with asymptomatic monoclonal gammopathy who underwent a BM biopsy may indicate that the latter exam may provide useful information and could be included in the standard initial workup of these individuals. Disclosures: No relevant conflicts of interest to declare.

Monitoring Minimum Residual Disease In Multiple Myeloma Patients By LC-MS/MS

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3152-3152
Author(s):  
H. Robert Bergen ◽  
David L Murray ◽  
Diane F. Jelinek ◽  
Renee C. Tschumper ◽  
David R Barnidge ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bone Marrow Biopsy ◽  
Light Chain ◽  
Plasma Cells ◽  
Residual Disease ◽  
Patent Application ◽  
Sds Page ◽  
Minimum Residual ◽  
M Spike

Abstract Proteomics with great sensitivity and specificity effectively analyzes proteins by prior tryptic digestion and subsequent analysis by LC-MS/MS of the tryptic digest. We have utilized this approach in the development of a LC-MS/MS method to characterize minimum residual disease in multiple myeloma. The abundant antibodies produced by multiple myeloma plasma cells are identical and appear as a spike (M-spike) upon protein electrophoresis. The M-spike and histological examination of the bone marrow constitute part of the myeloma diagnostic repertoire. Upon treatment, myeloma cells and the antibodies they produce are reduced in number and amount and become increasingly hard to detect. The bone marrow biopsy serves as the “gold standard” test for clinical remission. We have developed a sensitive test for the presence of the monoclonal antibody produced by the plasma cells which may serve as a substitute for invasive bone marrow biopsy. We have focused on tryptic peptides comprising the variable CDR regions of the Ig light chains that are unique to each patients antibody clone. Utilizing 2-5 µL of patient plasma/serum from the initial M-spike sample we have utilized SDS-PAGE to yield a crudely purified immunoglobulin light chain. The light chain band is isolated, reduced, alkylated and trypsin digested with subsequent LC-MS/MS analysis to identify CDR specific tryptic peptide(s). These can be identified as variable peaks (elution time and mass) in a base peak ion chromatogram where constant region peptides of either lambda or kappa light chains (clone dependent) serve as “internal standards” for identifying the CDR tryptic peptides. The peptide’s mass and its corresponding MS/MS spectra are unique to this CDR tryptic peptide and this patient’s clone. The unique diagnostic peptide is isolated in subsequent samples by immunoaffinity purification of the target kappa/lambda clone, SDS-PAGE separation and LC-MS/MS analysis of the light chain gel band. An extracted ion chromatogram is generated based upon the CDR peptides identified in the initial analysis of the M-spike sample. In patients in clinical remission the presence of a significant signal from the targeted peptides indicates that targeting a CDR peptide from the M-spike protein is more sensitive than currently available diagnostic tools including immunofixation. Comparison of this test to the gold standard bone marrow biopsy will be examined. Disclosures: Barnidge: Mayo Foundation: provisional patent application for technology, provisional patent application for technology Patents & Royalties.

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).

Spontaneous Tumoural Regression in a Patient with t(4;14) Translocation Multiple Myeloma. A Case Report.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4777-4777
Author(s):  
Noemi Puig ◽  
Christine Chen ◽  
Joseph Mikhael ◽  
Donna Reece ◽  
Suzanne Trudel ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Case Report ◽  
Bone Marrow Biopsy ◽  
Peripheral Blood ◽  
Low Dose ◽  
Plasma Cells ◽  
Protein Electrophoresis ◽  
Urine Collection ◽  
Normal Limits

Abstract INTRODUCTION Despite recent advances, multiple myeloma continues to be an incurable malignancy, with a median overall survival (OS) of 29–62 months. A shortened survival is seen in myeloma patients having a t(4;14) translocation either with standard or high-dose chemotherapy (median OS 26 and 33 months, respectively). CASE REPORT A 60 year-old female was found to have a high ESR (121mm/h) and low hemoglobin (113g/L) in December 2005. Further work-up led to the diagnosis of stage 1A (Durie-Salmon) multiple myeloma on the basis of the following investigations: a protein electrophoresis showed IgG 12.2g/L, IgA 23.4g/L and IgM 0.33g/L with an IgA-kappa paraprotein; a bone marrow biopsy revealed 20–30% infiltration with atypical plasma cells, kappa restricted; IGH-MMSET fusion transcripts were detected by RT-PCR, consistent with the presence of t(4;14) positive cells in the specimen; a metastatic survey showed generalized osteopenia throughout the axial skeleton and multiple subtle permeative lucencies in the proximal humeral diaphyses bilaterally. A 24-hour urine collection showed 0.05g/L proteinuria with no Bence-Jones proteins detected. Her peripheral blood counts were as follows: hemoglobin 118g/L (MCV 91fL), platelets 275 bil/L and white blood cells 6.6 bil/L with 3.9 neutrophils and 1.8 lymphocytes. Her electrolytes and calcium were within normal limits but she had a slightly elevated creatinine at 107umol/L (normal <99). Her b2-microglobulin, C-reactive protein and albumin were all normal at 219nmol/L (normal ≤219), 4mg/L (normal ≤12) and 36g/L (36–50) respectively. No active therapy was recommended apart from monthly PAMIDRONATE for permeative lucencies. Her past medical history was significant for an IgA cryoglobulinemia diagnosed in 1985 when she presented with arthritis, purpura and Raynaud’s phenomenon. Her cryocrit has been ranging from 0–25% over the years; most recently still at 5%. She did not require any treatment until 1989 when she was started on low dose-steroids. Her flares consist mainly of lower limbs arthritis and purpura and they have been treated with intermittent PREDNISONE 5–7.5mg per day. A progressive drop in her M-protein has been documented since June 2006 with her most recent protein electrophoresis revealing no paraprotein, quantitative IgG is 7.7g/L, IgA 2.23g/L and IgM 0.63g/L. A bone marrow biopsy has shown less than 5% plasma cells. Her peripheral blood counts and biochemistry remained within normal limits and her skeletal survey is unchanged. A 24-hour urine collection shows no significant proteinuria (0.07g/L). Her free light chains assay revealed kappa 13.8mg/L and lambda 11.0mg/L with a ratio kappa/lambda 1.3. CONCLUSIONS We have documented tumoural regression in a patient with IgA-kappa multiple myeloma and t(4;14) only receiving intermittent low dose PREDNISONE and monthly PAMIDRONATE. This exceptional phenomenon has been well described with other malignancies such as testicular germ cell tumours, hepatocellular carcinomas and neuroblastomas; however, to the best of our knowledge, only in 2 cases of multiple myeloma. The unusual nature of this finding is highlighted by the presence of the t(4;14) in the plasma cells, known to be associated with more aggressive disease. The underlying mechanisms, speculated to be immunological for most of the other cancers, remain completely unknown in this case.

Renal Heavy Chain and Heavy+Light Chain Amyloidosis: A Report of 17 Cases and Comparison with Renal Light Chain Amyloidosis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3992-3992 ◽  
Author(s):  
Samih H. Nasr ◽  
Samar M. Said ◽  
Anthony M. Valeri ◽  
Sanjeev Sethi ◽  
Lynn D. Cornell ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Serum Creatinine ◽  
Light Chain ◽  
Cardiac Involvement ◽  
Plasma Cells ◽  
Kidney Biopsy ◽  
P Value ◽  
Fat Pad ◽  
Monoclonal Protein ◽  
Light Chain Amyloidosis

Abstract Abstract 3992 Little is known about the rare entities of heavy and light chain amyloidosis (AHL) and heavy chain amyloidosis (AH). In this study, we report the renal and hematologic characteristics, pathology, and outcome of 17 patients with renal AH/AHL including 5 with AH (4 IgG and 1 IgA) and 12 with AHL (7 IgGλ, 3 IgAκ, 1 IgAλ, and 1 IgMλ), and compare them with 202 patients with renal AL amyloidosis (AL) diagnosed during the same time period. All cases were diagnosed by kidney biopsy that showed Congo red-positive deposits. Amyloid typing was done by laser microdissection and mass spectrometry (LMD/MS) (12 patients) or by immunofluorescence (5 patients). All patients with renal AH/AHL were Caucasians, with a M:F ratio of 2.4 and a median age at biopsy of 63 years. Compared with patients with renal AL, those with renal AH/AHL had less frequent concurrent cardiac involvement, higher likelihood of having circulating complete monoclonal Ig, lower sensitivity of fat pad biopsy and bone marrow biopsy for detecting amyloid, higher incidence of hematuria, and better patient survival. The hematologic and renal responses to chemotherapy were comparable to renal AL. In 42% of patients, AH/AHL could not have been diagnosed without LMD/MS. In conclusion, renal AH/AHL is an uncommon but under-recognized form of amyloidosis, and its diagnosis is greatly enhanced by the use of LMD/MS for amyloid typing. The accurate histological diagnosis of renal AH/AHL and distinction from AL may have important clinical and prognostic implications. Table 1. Demographics and hematologic characteristics AH/AHL AL p value No. of patients 17 202 Gender: Male/female 12/5 (71%/29%) 126/76 (62%/38%) 0.61 Age, median (range) 63 (50–77) 62 (36–86) 0.73 Additional organ involvement 8 (47%) 126 (62%) 0.3 Cardiac involvement 3 (18%) 100 (50%) 0.01* % of plasma cells in bone marrow, median (IQR) 8 (5–15) 6 (5–10) 0.82     ≥30 plasma cells 4 (24%) 11/198 (6%) 0.02* Positive SPEP/SIF for paraprotein 15 (88%) 158/200 (79%) 0.53     Presence of whole monoclonal protein on SPEP 14 (82%) 108/200 (54%) 0.04* Positive UPEP/UIF for paraprotein 13/16 (81%) 158/189 (84%) 0.73     Presence of whole monoclonal protein on UPEP 10/16 (63%) 61/189 (32%) 0.03* Abnormal serum FLC ratio (<0.26 or >1.65) 9/12 (75%) 150/188 (80%) 0.71 Markedly abnormal FLC ratio (< 0.125 or > 8) 5/12 (42%) 100/188 (53%) 0.55 Positive bone marrow for amyloid 6/16 (38%) 135/183 (74%) 0.004* Positive fat pad biopsy for amyloid 2/14 (14%) 105/145 (72%) <0.001* IQR, interquartile range. Table 2. Renal characteristics at kidney biopsy AH/AHL AL p value No. of patients 17 202 24h urine protein in g, median (IQR) 5.1 (3.2–9.0) 6.0 (3.2–10.0) 0.9 Full nephrotic syndrome 9/16 (56%) 132/197 (67%) 0.42 Serum albumin in g/dl, median (IQR) 2.7 (2.2–3.3) 2.5 (1.9–2.9) 0.29 % albuminuria on UPEP, median (IQR) 68 (61–72) 70 (60–76) 0.47 Serum creatinine in mg/dl, median (IQR) 1.4 (1.1–2.1) 1.2 (0.9–1.8) 0.25 Serum creatinine >1.2 mg/dl 10/16 (63%) 92/201 (46%) 0.3 eGFR, median (IQR) 47 (27–67) 58 (36–75) 0.29 Decreased eGFR 10/16 (63%) 103/201 (51%) 0.44 Microscopic hematuria 9/16 (56%) 44/169 (26%) 0.02* IQR, interquartile range. Disclosures: No relevant conflicts of interest to declare.

Responses Assigned Using Heavy+Light Chain Assessments Have Better Clinical Correlation with Outcome Than Those Using Current IMWG Criteria for Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3245-3245
Author(s):  
Mauricette Michallet ◽  
Colette Chapuis-Cellier ◽  
Christine Lombard ◽  
Mohamad Sobh ◽  
Thomas Dejoie ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Research Funding ◽  
Complete Response ◽  
Clinical Impact ◽  
Similar Response ◽  
Consolidation Therapy ◽  
Color Flow ◽  
Multiple Myeloma Patient ◽  
Monoclonal Protein

Abstract Introduction: Stratification of multiple myeloma patient responses by reductions in monoclonal component is based upon reliable, historic outcome data. With the introduction of novel agents, a greater number of patients are achieving hitherto unthought-of responses, with many expecting to meet the requirement for VGPR or greater. Multiple factors can impact the quantification and assessment of response in patients achieving deep responses including the influence of IgG recycling, accuracy of quantitation against an increasing polyclonal background and the presence of monoclonal immunotherapies. Alternative strategies for monoclonal protein measurement include heavy+light chain (HLC) immunoassays. Here for the first time we compare the consistency of response assignment between the two methods and evaluate the clinical impact of discordance. Methods: Sera from 509 newly diagnosed intact immunoglobulin multiple myeloma (IIMM) patients enrolled onto IFM-2009 trial were available (median age was 59 (range: 33-66) years, follow-up 30 (3-56) months). Two patients arms were treated with RVDx3+ASCT+RVDx2 or RVDx8, followed by 12 months Lenalidomide maintenance. Responses were assigned at the end of consolidation therapy according to IMWG criteria using changes in monoclonal protein concentrations measured by either SPE or dHLC (clonal - non clonal). Complete response (CR) was assigned by either method by the absence of monoclonal protein on IFE or a normal HLC ratio (HLCr), respectively, and <5% BM plasma cells. HLC-pair suppression was defined as levels of the non-clonal HLC (e.g. IgGλ in an IgGκ patient) below the reference range (IgGκ <3.84g/L; IgGλ <1.91g/L; IgAκ <0.57g/L; IgAλ <0.44g/L). Minimal residual disease (MRD) was assessed by 7-color flow cytometry at the end of consolidation therapy. Results: IFE and HLCr concordantly identified clonality in 99% patients. In 463 patients followed until the end of consolidation we found moderate agreement in response assignment between the two tests. HLC gave similar response assignments to electrophoretic tests in patients with poor response (≤PR, 76/96; 79%) or complete response (≥CR, 130/142; 92%). However in patients achieving VGPR there was considerable discordance between methods for response assignment (102/225; 45%). Having identified discordant results for VGPR we sought to assess the clinical accuracy of the responses assigned within this group. Of the 225 patients with standard VGPR, HLC response assignment varied (PR (18/225), VGPR (102/225) and ≥CR (105/225)). Median PFS for patients achieving standard VGPR was 34.5 months; responses by HLC further described these patients into those with poorer PFS (PR, median PFS=21.3 months (95%CI: 9.0-33.7)); VGPR (PFS=28.9 months (95%CI: 25.1-32.6)), and those with improved outcomes (CR, median PFS not reached); p<0.0001 (Figure 1). This suggested that the response assigned by electrophoresis could be refined by HLC analysis. By contrast, responses assigned by electrophoretic methods offered no added clinical value in patients achieving VGPR (log-rank: p=0.724) or ≥CR (log-rank: p=0.402) by HLC assessment. Furthermore, an abnormal HLCr post-consolidation had a greater concordance with MRD+ assessment (78% positive) compared to IFE (51% positive); whereas both a normal HLCr and negative IFE displayed similar agreement with MRD- assessment (88% and 94% negative, respectively). Finally we assessed the clinical impact of recovering polyclonal immunoglobulin levels after consolidation therapy. In 142 patients with complete responses, HLC-pair suppression (n=15, median PFS=35.1 months (95%CI: 20.9-49.2) and severe suppression (n=7, median PFS=22.9 months (95%CI: 16.6-29.2)) were associated with poorer outcomes (p=0.060 and p=0.004, respectively). Conclusions: In patients achieving a poor or exceptional response there was good agreement between HLC and standard response assignment. For patients achieving a VGPR we suggest that HLC response assignment may be beneficial, therefore overall the assessment could be used to augment or replace electrophoresis. The prognostic significance of HLC responses seems to be partly dependent in the patient's ability to recover their immune system, as determined by normalisation of non-clonal HLC levels. Figure 1 Figure 1. Disclosures Michallet: Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Astellas Pharma: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Genzyme: Consultancy, Honoraria. Attal:sanofi: Consultancy; janssen: Consultancy, Research Funding; amgen: Consultancy, Research Funding; celgene: Consultancy, Research Funding. Moreau:Novartis: Honoraria; Celgene: Honoraria; Takeda: Honoraria; Janssen: Honoraria, Speakers Bureau; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria. Avet-Loiseau:janssen: Consultancy; sanofi: Consultancy; amgen: Consultancy; celgene: Consultancy.

scholarly journals Significance of Bone Marrow Plasma Cell Percentage in Patients with Monoclonal Gammopathy of Unknown Significance Developing Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5688-5688
Author(s):  
Mona L Vekaria ◽  
Bharat Rao ◽  
Philip Kuriakose
Keyword(s):  
Risk Factors ◽  
Bone Marrow ◽  
Bone Marrow Biopsy ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Time To Progression ◽  
Bone Marrow Biopsies ◽  
Monoclonal Protein ◽  
Cell Percentage

Abstract Introduction: Monoclonal gammopathies are characterized by the detection of a monoclonal immunoglobulin in the serum or urine and underlying proliferation of a plasma cell/B lymphoid clone. (1) Patients with monoclonal gammopathy of undetermined significance (MGUS) have a clonal plasma cell population in the marrow (<10%) and secrete a monoclonal protein in the serum (<3g/dL) and/or urine. However, they lack clinical features of overt Multiple Myeloma (MM) (lytic bone lesions, anemia, renal impairment and hypercalcemia). In a study from the Mayo Clinic, 59 of 241 patients with MGUS (24%) developed MM over a period of 22 years. (2) The interval from recognition of monoclonal protein to diagnosis of MM ranged from 2-29 years, indicating that patients with MGUS need to be followed indefinitely. Many risk factors have been looked at to identify those with MGUS who are at the highest risk to progress into MM. We hypothesize that a higher number of plasma cells would correlate with a greater risk of progression to MM and sought to find out if this could be documented by arbitrarily dividing patients between < or ≥5% plasma cells seen on initial bone marrow biopsy. Methods: We retrospectively reviewed patients diagnosed with MGUS at Henry Ford Hospital between 1999-2013 who underwent a bone marrow biopsy for documenting plasma cell percentage. In addition to this, we also recorded serum hemoglobin, calcium, creatinine, monoclonal protein type and amount, serum free light chains, beta-2 microglobulin and urine for monoclonal protein at the time of diagnosis of MGUS as well as last completed values. For patients that had skeletal surveys we noted if lytic lesions were present at diagnosis, as well as cytogenetics and karyotype evaluations on bone marrow biopsy samples, if completed. Results: 120 patients with bone marrow biopsies were reviewed. Out of this 17 patients were noted from initial bone marrow biopsy to have ≥10% plasma cells. The remaining 103 patients were categorized as having MGUS. While we were not able to complete full statistical analyses, we did note that 14 of these 103 (13.6%) patients went on to develop overt MM. Further evaluation of these patients revealed that 8 of 14 (57%) had bone marrow biopsies showing ≥5% plasma cells. Interestingly the average time to progression into MM in this subgroup was 1,879 days whereas in the 6 of 14 (43%) with bone marrow biopsy showing <5% plasma cells had average time to progression into MM of 1,965 days. Abnormal cytogenetics and karyotypes of the bone marrow biopsy were also seen in 37.5% of the subgroup of patients with ≥5% plasma cells whereas it was only seen in 16.7% of the subgroup of patients with <5% plasma cells. With statistical data analyses we hope to prove significance in the above collected data as well as make further correlations in regards to risk factors in patients with MGUS. Conclusion: While we have not been able to complete full statistical analyses of the collected data yet, basic review of the above patients with MGUS and ≥5% plasma cells in the bone marrow biopsy showed a trend to develop MM faster by an average of 86 days than those that had <5% plasma cells. These same patients also were more likely to have abnormal cytogenetics and karyotypes of their bone marrow biopsies. There is a need for further investigations to be done in patients with MGUS and higher risk features. It is important that hematologists be able to recognize a high risk MGUS patient as this would lead to closer monitoring and consideration for earlier aggressive treatment to potentially delay progression into overt MM. Disclosures No relevant conflicts of interest to declare.

scholarly journals Bence Jones Proteinuria in Smoldering Multiple Myeloma As Predictor Marker of Progression to Symptomatic Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3369-3369 ◽  
Author(s):  
Veronica Gonzalez de la Calle ◽  
Ramon Garcia-Sanz ◽  
Eduardo Sobejano ◽  
Enrique M. Ocio ◽  
Noemi Puig ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Light Chain ◽  
Plasma Cells ◽  
Symptomatic Disease ◽  
Risk Of Progression ◽  
Bone Marrow Plasma ◽  
Active Disease ◽  
Bence Jones Proteinuria

Abstract BACKGROUND Smoldering multiple myeloma (SMM) is a plasma cell proliferative disorder with no related organ or tissue impairment. It is associated with a risk of progression to symptomatic multiple myeloma (MM) of approximately 10% per year. Several prognostic factors for the progression to active disease have been identified, such as those defined by the Mayo Clinic including the proportion of bone marrow plasma cells, the serum monoclonal protein level at diagnosis and the serum immunoglobulin free light chain ratio (FLC); or those defined by the Spanish Group including the proportion of bone marrow aberrant plasma cells assessed by flow cytometry plus immunoparesis. The presence of Bence Jones (BJ) proteinuria is a myeloma feature associated with renal function and tumor burden as well. There is lack of evidence about the role of BJ proteinuria in SMM as predictor marker of progression to symptomatic disease. AIMS The goal of the present study was to investigate the role of the presence of Bence Jones proteinuria at diagnosis in SMM as predictor of progression to symptomatic disease. METHODS We reviewed 147 medical records of SMM patients from area of Castilla y León (Spain), diagnosed between 1983 and 2013, according to the criteria of the International Myeloma Working Group. The primary endpoint was time to progression to active multiple myeloma (hypercalcemia, renal insufficiency, anemia or bone lesions). RESULTS 147 patients with SMM were included in the analysis. The median age at diagnosis was 69 years-old (range: 34-90).The serum M-protein at diagnosis ranged from 1 to 26 g/l (median,25). 70% of SMM were Ig G subtype. The proportion of bone marrow plasma cells ranged from 1% to 55% (median, 14). In 64 % of SMM, the percentage of aberrant plasma cells assessed by flow cytometry was superior to 95% and 51% had immunoparesis. Bence Jones proteinuria was detected at diagnosis in 40 patients (27%) and the average amount of urinary monoclonal light chain was 236 mg per 24h. Of those patients, 58% had a monoclonal kappa light chain. The FLC ratio was assessed in 18 patients and it was abnormal (<0.26 or >1.65) in 83% of them. The median level of involved Immunoglobulin was 88.5 mg/l (range, 13-1200) and the median ratio of involved to uninvolved was 10.8 (range, 2.2-3360). In 4 patients, FLC ratio was greater than 100. At a median follow-up of 54 months, progression to active disease occurred in 49%. Anemia was the most common CRAB feature at the time of progression. Median time to progression (TTP) to symptomatic disease in the whole series was 63 months. SMM with BJ proteinuria had a significantly shorter median TTP to active disease as compared with patients without BJ proteinuria (21.7 months vs 82.9 months ;HR: 2.44, IC 95%: 1.48-4.02; p<0.001). The progression risk at 2 years in the BJ group of SMM was 53%. Multivariate analysis selected BJ proteinuria at diagnosis as an independent variable for progression to symptomatic MM (HR: 2.47, IC 95%: 1.32-4.63; P=0.005). Using this independent variable, we identified 4 risk categories according to amount of urinary monoclonal light chain: 0 mg per 24h; 1-250 mg/24h; 251-500 mg/24h ; or more than 500 mg/24h, with a median TTP of 83, 37, 16 and 7 months, respectively; p <0.001. CONCLUSIONS The presence of Bence Jones proteinuria at diagnosis in SMM patients is associated with significantly higher risk of progression to active MM (53% risk of progression at 2 years). Moreover, the presence of more than 500 mg of BJ proteinuria can be considered as a marker for the identification of ultra high risk SMM. Disclosures No relevant conflicts of interest to declare.

scholarly journals DETERMINATION OF PARAPROTEIN IN SERUM AND URINE BY ELECTROPHORESIS FOR DIAGNOSING MULTIPLE MYELOMA (MM), EXPERIENCES FROM THE PHF UNIVERSITY CLINIC OF HEMATOLOGY FOR THE PERIOD FROM 2015 TO 2017

2019 ◽  
Vol 34 (4) ◽  
pp. 895-901
Author(s):  
Bosko Gjorgjievski ◽  
Dino Karpicarov ◽  
Biljana Gjorgjeska
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cells ◽  
Bone Cancer ◽  
Study Data ◽  
World Health ◽  
Blood Calcium ◽  
Health Organization ◽  
Serum And Urine

Introduction: Multiple myeloma is a clonal disorder characterized by the proliferation of mature B cells (plasma cells) in the bone marrow i.e. the appearance of monoclonal immunoglobulin fraction (M component, paraprotein) in the serum or occasionally only during electrophoresis, in the urine. Generally, multiple myeloma is the most common primary bone cancer which can be defined as a malignant tumor of the bone marrow. Regarding the benign form (MGUS, monoclonal gammopathy of undetermined significance), it should be noted that it is about 100 times more common than the myeloma. In order to diagnose this disease, serum and urine are examined by electrophoresis because this technique firstly enables the separation of the proteins and then the detection of the desired group of proteins, in the specific case, the paraprotein group. However, the presence of such proteins in serum or urine is not always a sign for multiple myeloma, so in order to diagnose this disease, additional tests need to be done. These tests include: determination of the number of blood cells, determination of the level of blood calcium, determination of the level of urea and creatinine, determination of the percentage of plasma cells in the bone marrow. Besides these tests, the usual additional test includes detection of β–2–microglobulin, which is another protein that can be produced by multiple myeloma cells.Aims of the study: Overview of the diagnosis of multiple myeloma by determination of the paraprotein in serum or urine by electrophoresis; Determination of the prevalence of multiple myeloma in patients on the territory of the Republic of N. Macedonia from 2015 to 2017; Analysis of the obtained data in relation to the gender and the age of the patients.Materials and methods: For the purpose of this study, data obtained from multiple myeloma patients, diagnosed and treated at the PHF University Clinic of Hematology, were analyzed. The data were collected over a period of three years (from 2015 to 2017). The study included patients over 40 years of age. The entire research was done in the laboratory of PHF University Clinic of Hematology.Results: According to the research, 19 patients with multiple myeloma were registered in 2015, 22 patients with multiple myeloma were registered in 2016 and 25 patients with multiple myeloma were registered in 2017. In terms of gender, this disease is more common in men and in terms of age, the same disease is most prevalent in patients between 70 and 90 years of age.Conclusion: The incidence of multiple myeloma is approximately 5 to 7 patients per 100,000 persons annually. The disease data obtained in this study are identical to those of the World Health Organization (WHO). In most patients who were diagnosed with multiple myeloma, renal dysfunction was also observed.

Sign in / Sign up

Export Citation Format

Share Document