Bence-Jones Research Articles

EP35 Cryoglobulinaemic vasculitis: an uncommon complication of Sjögren’s syndrome

EP35 Cryoglobulinaemic vasculitis: an uncommon complication of Sjögren’s syndrome

Does the Sea Star Discriminate Bence - Jones protein From Rat Igg as Antigens?

Immunocompetent cells were described in the sea star Asterina gibbosa: they recognize specifically various antigens as HRP (Horse-radish peroxydase) ,Alkalin phosphatase, trypsin ....On the other hand when certain Asterina gibbosa were immunized with Bence-Jones protein , other ones with Rat IGG: a crossed immune reaction occurs. The potential sea star immune system is not broad enough to detect such antigens.

Giant Solitary Plasmacytoma of Skull: A Case Report

Plasmacytoma is a tumor arising from plasma cell, which mainly grows within soft tissue or within axial skeleton, when it is present as a discreet solitary mass it is called as solitary plasmacytoma & it is rare, we report a 46 years male, presented to us with the complaints of painless swelling in the left frontoparietal region which is about 8.6x6.5cm in diameter, Magnetic resonance imaging revealed an extra axial mass in fronto parietal region with overlying bone destruction mimicking meningioma with bony erosion, we did frontoparietal craniectomy and complete resection of tumor with bony margin subsequently cranioplasty was also done, histopathology of which revealed plasmacytoma,after that we did urinary bence jones protein which was negative.
 Bang. J Neurosurgery 2020; 10(1): 106-110

Bence-Jones Protein, Rat IGG, H.R.P, Alkaline Phosphatase, Bovine Serum Albumine used as Antigens in the Immune Response of the Sea Star.

Immunocompetent cells were described in the sea star Asterina gibbosa: they recognize specifically various antigens. In the present work, Asterina gibbosa were immunized with Bence-Jones protein, other ones with Rat IGG, at last certain with H.RP (Horse-radish Peroxydase) and the last ones with Alkaline Phosphatase: a crossed immune reaction occurs between Rat IGG and B.J protein, but not between B.J and H.R.P not between Rat IGG and H.R.P and not between Alkaline Phosphatase and B.J, not between Alkaline Phosphatase and Rat IGG, used as antigens.

P0244OVERTURNING THE CONVENTIONAL PYRAMID OF AL AMYLOIDOSIS MANAGEMENT: DARATUMUMAB ADMINISTERED AS MONOTHERAPY IN SEVERE PATIENTS WITH BIOPSY PROVEN RENAL INVOLVEMENT

Abstract Background and Aims Immunoglobulin light chain amyloidosis (AL) with multi-organ involvement is characterized by poor outcome. Current treatment of AL targeting the underlying plasma cell clone has been adapted from the multiple myeloma (MM). Novel powerful drugs are expanding the therapeutic options. Daratumumab is a first-in-class anti-CD38 human antibody (IgG1κ) which proved to be effective in combination with bortezomib in MM refractory to conventional bortezomib-based regimens. Its effectiveness as a single agent and its safety in the treatment of AL amyloidosis is under study. Aim of the study: This study reports the experience with Daratumumab monotherapy in a series of severe patients with AL amyloidosis and multiorgan and biopsy-proven renal involvement. Method Five patients (2 males and 3 females), mean age 64 years (range 52-69) were treated with Daratumumab following antibody testing and extended RBC antigen phenotyping. Treatment protocol was as follows: 16 mg/kg Daratumumab i.v. administered weekly for 8 weeks, then 8 times every two weeks, and then monthly for 1 year. Premedication included oral paracetamol, and i.v. chlorphenamine and methylprednisolone. Results In patient #1, in dialysis, who was refractory to conventional therapies Daratumumab administration resulted in normalization of the FLC ratio with disappearance of serum M-component and Bence-Jones (BJ) proteinuria. In patient #2 who had a relapsing disease, Daratumumab treatment resulted in a rapid decrease of proteinuria (from 6.8 to 2.7gr/24 hours at the 16th dose) and N-terminal propeptide (NT-pro-BNP) levels (from 1844 pg/ml to 330 pg/ml) with disappearance of serum M-component and BJ proteinuria and normalization of the FLC ratio. Patient #3 was treated front-line. He had an impressive decrease of proteinuria from 9.3 to 2.2 gr/24 hrs and NT-proBNP levels (from 850 pg/ml to 225 pg/ml) with normalization of FLC ratio and disappearance of serum M-component. In patient #4, who was intolerant to conventional regimens, Daratumumab therapy resulted in decrease in proteinuria, disappearance of serum M-component and improvement in the FLC ratio, which were paralleled by a reduction of NT-proBNP levels. Patient #5 had a relapsing disease. Daratumumab achieved a decrease of proteinuria (from 2.5 to 1 gr/24 hrs9, a decrease of serum M-component with increase of FLC ratio (0.29, nv: 0.31 – 1.56). This was the only patient who experienced an infusion reaction during the first dose (grade 1). The 4 patients with still preserved renal function also showed renal response with sCr improvement or stabilization and a decrease in proteinuria levels These data were paralleled by the reduction of NT-proBNP values in the 3 patients with cardiac involvement. Conclusion Daratumumab monotherapy resulted in the disappearance of M-proteins in every patient with FLC ratio normalization in 4 out of 5 subjects and impressive decrease of proteinuria and pro-BNP values proving to be an effective therapeutic option for pretreated/naïve patients with severe AL with renal involvement.

Monoclonal gammopathy of renal significance: A novel combination of C3 glomerulopathy and light-chain proximal tubulopathy

Introduction: According to the recent International Kidney and Monoclonal Gammopathy Research Group Consensus report, the spectrum of monoclonal gammopathies of renal significance merges more than 12 conditions; and combinations of various patterns of monoclonal gammopathies of renal significance–associated kidney damage have already been described. We present a case of a previously unreported combination of C3 glomerulopathy and light-chain proximal tubulopathy. Case description: A 53-year-old Caucasian man presented with general weakness. Three years prior, a check-up revealed proteinuria and microhematuria, later accompanied by arterial hypertension, elevated serum creatinine, and a low serum C3 levels. On admission, his creatinine was 1.5 mg/dL; his protein excretion was 1900 mg/24 h with microhematuria at 150 hpf. His serum C3 was 79 mg/dL with a normal C4 level. Serum protein electrophoresis revealed an M-spike, immunochemistry confirmed monoclonal immunoglobulin G kappa secretion of 920 mg/dL, and traces of Bence–Jones protein kappa in his urine. A kidney biopsy showed mesangial hypercellularity with diffuse fine granular C3 mesangial expression and tubular atrophy with diffuse coarse granular kappa light-chain tubular epithelial cytoplasmic expression. Computed tomography did not reveal any destructive lesions. A bone marrow smear showed 5% plasma cells, and bone marrow cell flow cytometry demonstrated 87.4% of plasma cells with an aberrant phenotype. The patient was diagnosed with an monoclonal gammopathy of renal significance and administered bortezomib–cyclophosphamide–dexamethasone. After four courses, his monoclonal immunoglobulin G kappa secretion halved, but his serum creatinine and proteinuria remained almost unchanged. Chemotherapy was switched to lenalidomide–dexamethasone, and after five courses his immunoglobulin G kappa secretion decreased to traces, Bence–Jones protein was not observed and his urinalysis, serum creatinine, and C3 levels were detected as normal. Conclusion: The combination of kidney damage patterns, one of which was directly and the other indirectly associated with monoclonal gammopathy, complements the monoclonal gammopathies of renal significance spectrum. Chemotherapy led to a very good partial response and kidney function recovery.

Solitary Orbital Plasmocytoma: A Case Report and Review of Literature

Solitary orbital plasma cell neoplasm in the absence of multiple myeloma is very rare. We present here a case report of extramedullary plasmacytoma of the left orbital soft tissue in a 50-year-old woman whose thorough diagnostic workup was negative for multiple myeloma. The patient presented with rapidly increasing proptosis, swelling, and visual disturbances of the left eye for past 15 days. MRI of the orbit revealed an extra conal well-circumscribed homogeneously enhancing masse filling the superior and the temporal part of the left orbit without bone destruction Or intracranial extension. The patient underwent a subtotal resection and the pathological report revealed a plasma cell neoplasm. So, normal skeletal survey, absence of bone marrow involvement, absence of Bence-Jones protein, no anemia, no hypercalcemia, no renal disease, normal level of immunoglobulin’s all exclude the diagnosis of multiple myeloma. Since the visual acuity of the patient is well-preserved, so we have planned to treat her with local radiotherapy alone with 50 Gy.

The role of paraproteins in kidney damage in patients with lymphoproliferative diseases

Background.The course of lymphoproliferative diseases, in which the proliferation of a malignant clone is accompanied by the secretion of paraproteins, is often complicated by kidney damage. Perhaps kidney damage is associated with the physicochemical properties of monoclonal proteins.The objective of the studywas to determine the relationship between the type of monoclonal paraprotein, its level of secretion, and kidney damage in lymphoproliferative diseasesMaterials and methods.A retrospective analysis of the data of 108 patients with lymphoproliferative diseases accompanied by paraproteinemia and kidney damage was performed. The age of the patients was 31–86 years (median 62.5 years). 78 out of 108 patients were diagnosed with chronic kidney disease (CKD). CKD was diagnosed in accordance with the clinical guidelines of KDIGO 2012.Results.In patients with multiple myeloma, stage III CKD was diagnosed in 28 (35.9 %) cases, stage IV – in 14 (17.9 %), stage V – in 19 (24.4 %). High risk group for CKD included 10 (9.3 %) of 30 patients without CKD. 91 patients were diagnosed with concomitant diseases predisposing to the development of kidney damage. In the group of patients with paraproteinemic hemoblastosis in combination with CKD, the vast majority were patients with the presence of IgGκ and IgGλ blood paraproteins, free light chains (FLC), and Bence-Jones protein (BJ) in the urine. At the same time, patients with the secretion of IgDλ, IgAλ, IgAκ and IgMκ paraproteins were much less common. The highest level of pathological Ig of all classes and their structural components and fragments was observed in patients with stage III CKD, which is also characteristic of other laboratory markers in CKD. A negative correlation of glomerular filtration rate (GFR) with FLCκ in the blood (r = –0.21), GFR with BJκ (r = –0.35), GFR with FLCλ in the blood (r = –0.13), GFR c BJλ, which indicates a tendency to damage the kidneys of FLC and protein BJ.Conclusion.In patients with lymphoproliferative diseases accompanied by monoclonal secretion of paraprotein and kidney damage with the development of CKD, in most cases IgGκ, IgGλ, FLCκ and FLCλ were determined in the blood, and protein BJ in urine. IgAκ, IgAλ, IgMκ, IgMλ, IgDλ paraproteins were determined much less frequently in serum. The highest level of pathological Ig and their structural components was observed in patients with stage III CKD. No association with quantitative level, type of paraprotein, and kidney damage was found. The role of FLC and BJ protein in the development of nephropathy is noted. The results of the study also show that with the development of the disease and kidney damage with subsequent progression of the stage of CKD in patients with lymphoproliferative diseases and proteinemia, there is a tendency to a temporary decrease in proteinuria and a compensatory increase in the number of paraproteins in the blood. This can be considered as one of the compensatory pathophysiological mechanisms of the protective function of the kidneys.

Effect of Single Amino Acid Substitutions by Asn and Gln on Aggregation Properties of Bence-Jones Protein BIF.

The nature of renal amyloidosis involving Bence-Jones proteins in multiple myeloma is still unclear. The development of amyloidosis in neurodegenerative diseases is often associated with a high content of asparagine and glutamine residues in proteins forming amyloid deposits. To estimate the influence of Asn and Gln residues on the aggregation of Bence-Jones protein BIF, we obtained recombinant BIF and its mutants with the substitution of Tyr187→Asn (Y187N) in α-helix of CL domain, Lys170→Asn (K170N) and Ser157→Gln (S157Q) in CL domain loops, Arg109→Asn in VL-CL linker (R109N) and Asp29→Gln in VL domain loop (D29Q). The morphology of protein aggregates was studied at pH corresponding to the conditions in bloodstream (pH 7.2), distal (pH 6.5) and proximal renal tubules (pH 4.5) by atomic force microscopy (AFM) and small-angle X-ray scattering (SAXS). The Lys170→Asn replacement almost completely inhibits amyloidogenic activity. The Y187N forms fibril-like aggregates at all pH values. The Arg109→Asn replacement resulted in formation of fibril-like structures at pH 7.2 and 6.5 while the substitutions by Gln provoked formation of those structures only at pH 7.2. Therefore, the amyloidogenic properties are highly dependent on the location of Asn or Gln.

Regression of renal amyloid deposits by VAD therapy plus autologous stem cell transplantation in a patient with primary AL amyloidosis

We report a 58-year-old Japanese woman who presented with nephrotic syndrome. Steroid therapy and cyclosporine A administration were initiated, but hematological remission and renal response were not achieved. Renal biopsy revealed amyloid deposits in the mesangial region and the small arteries. Proteomic analysis based on laser microdissection and mass spectrometry showed that the amyloid deposits were composed of the constant region of the lambda light chain. She received vincristine, adriamycin, and dexamethasone therapy followed by high-dose melphalan and autologous stem cell transplantation, resulting in hematological complete remission and renal response with negative urinary Bence-Jones protein and proteinuria. Renal biopsy was performed four times during follow-up, demonstrating that amyloid deposits decreased gradually, while glomeruli showing global sclerosis increased from 3 to 62%. This case suggests that glomerular amyloid deposits can be cleared via tissue remodeling, if stem cells producing amyloid precursors are completely replaced by unrelated cells after stem cell transplantation.

Giant Solitary Plasmacytoma of Skull: A Case Report

Plasmacytoma is a tumor arising from plasma cell, which mainly grows within soft tissue or within axial skeleton, when it is present as a discreet solitary mass it is called as solitary plasmacytoma & it is rare, we report a 46 years male, presented to us with the complaints of painless swelling in the left front parietal region which is about 8.6x6.5cm in diameter, Magnetic resonance imaging revealed an extra axial mass in fronto parietal region with overlying bone destruction mimicking meningioma with bony erosion, we did frontoparietal craniectomy and complete resection of tumor with bone margin subsequent cranioplasty also done, histopathology of which revealed plasmacytoma,after that we did urinary bence jones protein which was negative
 Bang. J Neurosurgery 2019; 8(2): 115-118

Difficulties evaluating hematological response in patients with multiple myeloma and dialysis - dependent renal impairment

to determine serum free light chains (FLC) level by patients with multiple myeloma (MM) and dialysis - dependent renal impairment in which the amount Bence Jones (BJ) protein in the urine met the criteria of hematological response. This study included 13 MM with dialysis - dependent renal impairment patients (estimated glomerular filtration rate < 10 ml/min), whose urine BJ protein content was less than 200 mg/day after antimyeloma therapy (including 11 patients whose urine BJ protein content was less than 100 mg/day). The median serum concentration of monoclonal FLC was 608.7 (298-8380) mg/l. Thus, with trace amounts BJ protein in the urine serum content monoclonal FLC varied 28 times with the same degree of severity of renal failure. In patients with oliguria serum SLC content was significantly higher than in normal diuresis (1109 and 307 mg/L; p.

Plasmacytoma of Skull Mimicking Meningioma and Metastasis

Plasmacytoma is a tumor arising from plasma cell, which mainly grows within soft tissue or within axial skeleton. When it is present as a discreet solitary mass it is called as solitary plasmacytoma and it is rare. We report a case of 46 years male presented to us with the complaints of painless swelling in the left front parietal region which is about 8.6x6.5cm in diameter .Magnetic resonance imaging(MRI) revealed an extra axial mass in fronto parietal region with overlying bone destruction mimicking meningioma with bony erosion. We did fronto parietal craniectomy and complete resection of tumor with bone margin subsequent cranioplasty also done.Histopathology of which revealed plasmacytoma. After that we did urinary bence jones protein which was negative.

Plasmacytoma of Skull Mimicking Meningioma and Metastasis

Plasmacytoma is a tumor arising from plasma cell, which mainly grows within soft tissue or within axial skeleton. When it is present as a discreet solitary mass it is called as solitary plasmacytoma and it is rare. We report a case of 46 years male presented to us with the complaints of painless swelling in the left front parietal region which is about 8.6x6.5cm in diameter .Magnetic resonance imaging(MRI) revealed an extra axial mass in fronto parietal region with overlying bone destruction mimicking meningioma with bony erosion. We did fronto parietal craniectomy and complete resection of tumor with bone margin subsequent cranioplasty also done.Histopathology of which revealed plasmacytoma. After that we did urinary bence jones protein which was negative.

Contribution of Bence-Jones proteinuria to the monoclonal gammopathy diagnosis based on serum free light chains

Multiple Myeloma (MM) is the second most common hematological malignancy after non-Hodgkin lymphoma and is manifested by uncontrolled proliferation and accumulation of abnormal plasma cells in the bone marrow (BM). The incidence along with deaths associated with MM is on rise due to lack of an effective diagnosis at an early stage. The identification of MM decades ago marks the adoption of certain conventional markers such as plasma cell percentage in BM, serum protein electrophoresis for M-band and urinary Bence-Jones protein. This was then followed by utilization of β2 microglobulin and serum albumin for determining the staging of MM. The need for a better diagnostic or prognostic marker prompts researchers and hence, certain novel markers have been tested which includes extracellular matrix proteins, angiogenic factors, telomeres and telomerase along with the immune markers. Nowadays, proteomic and genomic studies are being performed to identify novel diagnostic and/or prognostic markers for MM. Followed by this, comes the emerging concept of liquid biopsy which allows easy and non-invasive detection of the disease. The liquid biopsy comprises of circulatory tumor cells along with the nucleic acids (microRNAs and cell-free DNA) released from the tumor cells in peripheral circulation which could be a true representation of BM. This review, hence, summarizes the emerging biomarkers involved in the diagnosis and prognosis of MM.

First Line Therapy in Multiple Myeloma: VAD vs Bortezomib -Dexamethasone

Multiple myeloma (MM) is typically sensitive to a range of cytotoxic agents, both as initial therapy and as relapsed disease treatment. Unfortunately, the responses are transient, and MM is not considered curable with the current approaches. This paper aims to assess the response to first line treatment of patients included in the study and their correlation with the negative prognostic factors in multiple myeloma: age over 60 years, male gender, anemia, hypercalcemia, elevated levels of creatinine, Beta 2 microglobulin, hypoalbuminemia and Bence-Jones proteins type. The study was conducted on a group of 105 patients admitted to the Hematology Department of the Municipal Emergency Clinical Hospital of Timisoara from 01 January 2013 until 31 December 2017. Twenty-seven patients received VAD regimen, while 78 underwent Bortezomib + Dexamethasone regimen as fist line therapy. When analyzing anthropometrical data, different gender distribution in the two groups of patients is seen, while a higher percentage of patients over 60 years is observed in both groups, with 77.7% in the VAD group (21 out of 27 patients) and 56.4% in the group treated with Bortezomib + Dexamethasone (44 out of 78 patients). Only some of the factors analyzed in our study statistically significantly influenced the response to treatment and the duration of survival, i.e.: age over 60 years, hemoglobin [10g/dL, platelets under 150000/mm3, creatinine ]2mg/dL, serum calcium ]10mg / dL, increased C-reactive protein, low serum albumin levels, high levels of Beta 2 microglobulin, total serum protein, as well as presence of cells in the peripheral smear. Defining a panel of negative prognostic factors that influence the evolution and response to multiple myeloma treatment would allow for tailoring of personalized therapies for each patient.

Nanoporous silica coupled MALDI-TOF MS detection of Bence-Jones proteins in human urine for diagnosis of multiple myeloma

Bence-Jones protein is a biomarker in urine for multiple myeloma. Traditional methods for urine Bence-Jones protein detection are either less-sensitive or laborious. Herein, we describe a new method for the detection of urine Bence-Jones protein using nanoporous materials and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Macroporous ordered silica foams (MOSF) were used to enrich proteins in urine, and then the materials-proteins composites were analyzed by MALDI-TOF MS. Based on the presence of specific mass spectrometric signals, Bence-Jones protein can be detected for the diagnosis of multiple myeloma. Twenty-one clinical positive and twenty-seven clinical negative urine samples were analyzed by the method. High sensitivity (95.24%, 20/21) and specificity (100%, 27/27) for the diagnosis of multiple myeloma were achieved. Compared to other methods for multiple myeloma diagnosis, e.g. immunofixation electrophoresis and immunonephelometry, our approach is more rapid, economical and convenient, which can be a new choice for the clinical diagnosis of Bence-Jones protein related diseases.

Bence-Jones protein as the form of nano-scaled β-stacked supramolecular aggregates

Abstract. The formation in β-structured protein aggregates in tissues and fluids of the body is one of the most dangerouse complications of various diseases. The most famous of them are amyloidoses, but they such deposits are observed at other, much more widespread, diseases. The generally accepted approach to amyloids’detectionis based on high-specific coloring by Congo Red dye. However, the Abbe's diffraction limit excludes the seeing of the objects smaller than 0.61 wavelengths (about 240 nm). Such nanoscale formations are capable to disrup the functioning of surrounding tissues, to causethe complications and recurrences of the disease, and to pass through biological barriers with the following accumulation in body’s fluids. It’s likely that these conditions are the cause of the urinary congophilia, that is associated with preeclampsia at pregnancy and chronic kidney disease. Nor the less suspicious object is the Bens-Jones protein that appears in the urine at multiple myeloma and some other diseases, which are in more or less extent,are related to the disturbance of protein metabolism.&#x0D; The purpose of this study was to clarify the aggregate state of the Bens-Jones protein as a possible β-structured supramolecular associate.&#x0D; Methods.The subject of the study was the freshly received urine from a patient with multiple myeloma. The presence of the Bens-Jones protein was checked by thermopacification of the acidified sample. For control, the urine was used by a healthy person with the addition of certain amounts of human serum albumin ("Reanal", Hungary) with a concentration of 0, 0.01, 0.1 and 1%.&#x0D; Result. The obtained data testify to the appropriateness of such a point of view and create preresquites for the expanding of diagnostic possibilities.&#x0D; Conclusions.The results obtained during the study testify to the peculiarity of the structure of the Bens-Jones protein, which is nano-sized beta-structured supramolecular

Predictors of Overall Survival for Multiple Myeloma Patients Depending on Transplant Status According to a Retrospective, Non-Interventional Study in Norway

IntroductionMultiple myeloma (MM) is the second most common hematological malignancy in Europe and the US. The median survival after diagnosis is approximately 4-5 years (Röllig et al The Lancet 2015), with recent improvement observed in younger (Kyle et al Expert Rev Hematol 2014) and older patients (Kumar et al Leukemia 2013). The improvement in outcomes of MM patients is largely due to the introduction of autologous stem cell transplant (ASCT) and novel treatments including proteasome inhibitors and immunomodulators. Norwegian guidelines state that the preferred frontline treatment for MM patients under 65-70 years old is ASCT, but this option may be limited by comorbidity. Here, we report results from a retrospective, non-interventional study using data collected at the MM registry at Oslo University Hospital (OUS), Norway. The aim was to describe patient and disease characteristics, overall survival (OS), and potential predictors of death for the study population in Norway.MethodsThe study period was from 1 Jan 2008 to 31 Dec 2015. Patients (n=169) aged 18 years or older at MM diagnosis and who were treated at OUS (ASCT or not) or in 1 of 5 regional hospitals (ASCT only, with ASCT received at OUS and other treatments received locally), during the study period, were included. Study entry was defined as date of MM diagnosis and follow-up started from study entry. End of follow-up occurred at the first of: end of study period, loss to follow-up, or death. Variables used were part of routine practice. Descriptive analysis was done at diagnosis for the overall population, for patients who received ASCT (n=100), and for those who did not receive ASCT at any time during the study period (n=69). At treatment line 1, Cox models were used to identify potential predictors for OS.ResultsIn the study, 55.6% of patients were diagnosed with MM at OUS and 25 of those patients (14.8% of total population) received ASCT. Patients who did not receive ASCT were older and included a larger percentage of women than in the transplant cohort (mean age non-ASCT 73.1±11.2 with 55.1% women and for ASCT 55.5±6.7 years with 45.0% women).More MM patients were diagnosed with Bence Jones (BJ) (21.9% of patients) or IgG type myeloma (54.4% of patients) than IgA type (20.1% of patients) (Table 1). Of transplant patients, more were of International Staging System (ISS) stage I or stage II than stage III MM, though 35.0% of patients were of unknown stage. Most non-transplant patients had unknown ISS stage, followed by stages II and III and the least number of patients were of stage I.Of the CRAB symptoms at diagnosis, most ASCT patients showed no hypercalcemia (80.0%), no renal impairment (90.0%), or no anemia (68.0%), and 34.0% presented with skeletal destruction (Table 1). Similarly, most non-transplant patients had no hypercalcemia (87.0%) and no renal impairment (79.7%) at diagnosis. Anemia and skeletal destruction were not measured in 24.6% of non-transplant patients. Of those with recorded results, more non-transplant patients had skeletal destruction than not and approximately the same number of non-transplant patients presented with anemia than not. High-risk cytogenic abnormalities, a criterion of the revised (R)-ISS, was unknown for most patients (80.5%).Median OS from start of treatment line 1 was 75.93 (90% confidence interval (CI): 68.23 to not reached) months for transplant patients and 34.20 (90% CI: 25.57-42.16) months for non-transplant patients. Variables including age group, sex, CRAB symptoms at diagnosis, type of first therapy, and type of MM at diagnosis were included in the Cox models per cohort, if they had a missingness of <20%. Hypercalcemia at diagnosis was a significant predictor for OS for the transplant cohort, while anemia at diagnosis gave a decreased risk of death. Hypercalcemia as well belonging to the older age groups (e.g., 61-70 years and 71-80 years) were significant predictors of death for the non-transplant patients (Table 2).ConclusionsFor MM patients in Norway, overall survival was much greater for patients receiving transplant in the first line. Hypercalcemia at diagnosis predicted death for both transplant and non-transplant cohorts and anemia at diagnosis was identified as a decreased risk of death for transplant patients, but not well-recorded for non-transplant patients. Belonging to an older age group (>71 or 80 years old) also was a significant predictor of death, but only for non-transplant patients. DisclosuresSchjesvold:Oncopeptides: Consultancy; Celgene: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy; Takeda: Consultancy, Honoraria; Bayer: Consultancy; Amgen: Consultancy, Honoraria, Research Funding; Adaptive: Consultancy; Janssen: Consultancy, Honoraria, Research Funding; Abbvie: Honoraria; Novartis: Honoraria. Jenna:Janssen-Cilag: Other: Employee of StatFinn & EPID Research, contracted by Janssen-Cilag. Sõnajalg:Janssen-Cilag: Other: Employee of StatFinn & EPID Research, contracted by Janssen-Cilag. Leval:Janssen-Cilag: Employment. Rana:Janssen-Cilag: Employment. Castren-Kortekangas:Janssen-Cilag: Employment. Borgsten:Janssen-Cilag: Employment.

Presentation Pattern, Diagnostic Markers, Management and Outcome of IgD Multiple Myeloma: A Systematic Review

Background:IgD multiple myeloma (MM) is a rare subtype contributing 2% of all multiple myeloma cases. Despite difficulty and delay in diagnosis, recent advances in the treatment of multiple myeloma in general also improved the outcomes for IgD myeloma subtype. The aim of this study is to summarize the data on presentation patterns, diagnosis, management approaches and outcomes for patients (pts) with IgD myeloma.Methods:A comprehensive literature search for articles published after December 2013 was performed using four databases: PubMed, Embase, Cochrane, and Clinicaltrials.gov. With initial search we identified 209 articles and after screening by two independent reviewers we included only 8 studies in the final analysis.Results:A total of 166 pts with IgD MM were included from 8 selected retrospective case series. Lambda (λ) was the predominant light chain sub-type in 136 patients (81.9%). Initial manifestations of IgD MM were Bence jones proteinuria (BJP>2 g/day-64.5%), renal dysfunction (63%), bone pain (55.9%), weakness, fatigue (34.2%) and extra medullary involvement (28.3%). Renal function was assessed by estimated glomerular filtration rate (eGFR<60 ml/min/1.73m2) in 54.3 % of patients and by serum creatinine level (Cr >2mg/dl) in 46.1% patients. Cytogenetic karyotype analysis in 56 pts using fluorescence in-situ hybridization (FISH) identified abnormal cytogenetics in 41 (73.2%) patients, cases were further classified as high risk (85.7%) and standard risk (14.3%). The patient characteristics and disease manifestations are mentioned in Table 1.Serum protein electrophoresis (SPEP) showed positive monoclonal spike (M) spike in 84% of the patients. The median M spike value for IgD MM was 9.42 g/l in a cohort of 17pts, (Djidjik et al.) which was lower as compared to IgG (median: 35 g/L) and IgA (median: 32 g/L) in this study. Abnormal serum free light chain ratio (sFLCR) was observed in 83% pts. Quantitative serum IgD levels were elevated only in 28% of the cases. Bone marrow (BM) plasmacytosis showing > 40% abnormal plasma cells was detected in 95.6% of the patients. N glycans are newly discovered biomarkers used for detecting abnormal protein glycosylation in MM patients. NG1(6)A2F and NG1(3)A2F were the two most significant N glycan markers for IgD MM patients with sensitivity of 95% & 95.2%, respectively and specificity of 95% & 78.6%, respectively. The prognostic significance of several other biomarkers studied in IgD MM is mentioned in Table 2.Treatment details were available for 149 patients and overall response rate (ORR) was seen in 125 (83.9%) patients while 24 (15.4%) patients had progressive or stable disease. The median overall survival (mOS) was between 9 - 62 months. Novel agents (NA) such as bortezomib, thalidomide and lenalidomide were given to 111 (74.4%) pts with the mOS between 15 - 38.6 months. Conventional agents (CA) such as melphalan, vinblastine, vincristine, epirubicin, and ifosfamide were given to 38 (25.5%) patients with mOS between 12.5 - 17 months. Data showed bortezomib based regimens resulted in a higher ORR (ORR=94%, CR=52%) compared to non bortezomib based regimens (ORR=77.8%, CR=27.7%) respectively. Stem cell transplant (SCT) was used in 37 (24.8%) patients with chemotherapy (NA=26, CA=11) which showed good response rate (ORR>90%,CR >60%). The comparison of response rate with different drugs is mentioned in the Table 3.Conclusion:N-glycan assay can overcome the limitations of SPEP and quantitative serum IgD assay in the diagnosis of IgD MM. This difficulty is posed by the lower concentrations of M spike ( SPEP) or lower-normal serum IgD value on quantitative serum assays, which can delay its diagnosis. Novel and conventional agents have good responses with ORR>90%, but mOS of conventional agents was lower when compared to novel agents. Bortezomib based regimens showed better responses when compared to non-bortezomib regimens. The best response (ORR=95%) was obtained with use of SCT in combination with novel agents. Serum free light chain levels, N glycan assay and serum IgD quantification were found to be the best prognostic markers for IgD MM. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.