Light Chain Deposition Disease Research Articles

Impact of Revised International Staging System 2 (R2-ISS) Risk Stratification on Outcomes of Patients with Multiple Myeloma Receiving Autologous Hematopoietic Stem Cell Transplantation

Background: The second revision of the International Staging System (R2-ISS) is a new and simple tool to risk stratify newly diagnosed multiple myeloma (NDMM) patients. Our aim in this study was to evaluate the utility of R2-ISS in NDMM patients who received upfront autologous hematopoietic stem cell transplantation (auto-HCT). Methods: We conducted a retrospective analysis of all NDMM patients who underwent upfront auto-HCT between 1988 and 2021 at MD Anderson Cancer Center and had available data for calculation of R2-ISS, including albumin, β-2 microglobulin, LDH, and fluorescence in-situ hybridization (FISH) analysis at diagnosis. High-risk cytogenetic abnormalities (HRCA) were t(4;14), del(17p), and 1q21 gain or amplification, as detected by FISH. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoint was hematological response after auto-HCT. Results: A total of 1291 patients were included, with a median age of 62 years (range 29 - 83) and 60% were male. Four hundred-and-nineteen patients (32%) had HRCA. Most patients received either bortezomib, lenalidomide, and dexamethasone (VRD) (34%) or carfilzomib, lenalidomide, and dexamethasone (KRD) (25%) induction regimens, and most patients (95%) received melphalan based conditioning. The distribution of R2-ISS stages in our cohort was as follows: 123 (10%) stage I, 471 (36%) stage II, 566 (44%) stage III, and 131 (10%) stage IV. A total of 1027 (80%) patients received post auto-HCT maintenance, mostly lenalidomide with or without dexamethasone (n = 785, 61%) (Table 1). With a median follow-up of 42.2 months (range 0.3 - 181.0) for the entire cohort, the median PFS was 73.0, 65.2, 44.0, and 24.8 months ( P < .001) and the median OS was 130.8, 128.5, 94.2, and 61.4 months ( P < .001) for patients with R2-ISS stages I, II, III, and IV, respectively (Figure 1). On multivariable analysis (MVA) for PFS, using R2-ISS stage I as the reference group, there was no significant difference for R2-ISS stage II (hazard ratio [95% CI], 1.11 [0.76-1.63]; P = .59), but there was a significant worsening in PFS for R2-ISS stage III (1.55 [1.05-2.29]; P = .028) and R2-ISS stage IV (2.04 [1.24-3.36]; P = .005). On MVA for OS, again using R2-ISS stage I as the reference group, there was no significant difference for R2-ISS stage II (1.33 [0.74-2.40]; P = .34) or R2-ISS stage III (1.75 [0.97-3.17]; P = .06), but there was a significant worsening in OS for R2-ISS stage IV (2.43 [1.18-5.01]; P = .017). On MVA, other measures significantly associated with worsening PFS were year of auto-HCT < 2010, lambda light chain disease subtype, presence of HRCA, prior MRD/response other than negative/≥CR, and not achieving MRD negative/≥ CR post auto-HCT. For OS, other measures significantly associated with worsening survival on MVA were presence of HRCA, HCT-CI > 3, having at least one bone lesion, not achieving CR at best response, and not receiving post auto-HCT maintenance therapy. Conclusion: Our study demonstrates that R2-ISS is a reliable prognostic tool for NDMM in a large cohort of patients who received standard anti-myeloma treatment, including modern induction regimens, upfront auto-HCT, and post-transplant maintenance.

Long Term Outcomes and Renal Response Following Autologous Stem Cell Transplantation for Light Chain Deposition Disease:a Retrospective Study on Behalf of the Cmwp of the EBMT

Background: There is a paucity of data concerning long-term outcomes following autologous stem cell transplantation (ASCT) for light chain deposition disease (LCDD). The goal of this retrospective study was to analyze the outcomes following ASCT in LCDD patients in terms of toxicity and efficacy with both hematological and renal responses. Methods: Adult patients who underwent a first ASCT for renal biopsy-proven LCDD (AL amyloidosis excluded) between the years 1995 and 2021 were selected from the EBMT registry. The probability of overall survival (OS) and progression-free survival (PFS) was estimated based on the Kaplan-Meier method and differences analyzed using the log-rank test. Engraftment with death as competing event and relapse and non-relapse mortality (NRM) were modeled using the crude cumulative incidence estimator and compared between groups with Gray's test. eGFR, measured at auto-HCT and 3 6, and 12 months was longitudinally modeled using linear mixed effects models. Results: There were 51 patients in 24 centres. 63% were male. The median year of diagnosis was 2011 (IQR: 2008-2015). The underlying plasma cell disorder was either myeloma (47%) or Monoclonal Gammopathy of Clinical Significance (MGCS, 50%), with 3% missing. The median bone marrow aspirate plasmacytosis was 10% (IQR: 7.8-20) and the immunoglobulin isotypes were as follows: Light Chain only 69% (Kappa 82%, Lambda 18%), IgG 24%, IgA 2%, IgD 2% and non-secretory 2%. Of 17 patients with cytogenetic data, 3 were t(11;14) and one del 17p. All 40 patients with data on disease involvement had renal involvement, and, of these, 3 had cardiac and 2 hepatic involvement. At diagnosis, the median serum creatinine was 233 µmol/L (IQR:159-467), median proteinuria was 1,813 mg/24h (IQR:445-5974) and 16% had bone lesions. 42 of 44 patients with available data had received an induction regimen (93% bortezomib-based) and the hematological responses prior to transplant were as follows: CR 12%, VGPR 29%, PR 31%, MR/SD 16%, and relapse/progression 6% (missing: 6%). A total of 59% were transplanted in or after 2012. The median age at transplant was 55 years (IQR:49-61). The median time from diagnosis to transplant was 7.4 months (IQR:5.5-13.0) and 42% were on dialysis at the time of transplant. The Karnofsky Performance Score (KPS) was >80 in 79%. The Melphalan conditioning dose (mg/m 2) was 100 (23%), 140 (55%) or 200 (21%). The median number of infused CD34+ cells x 10 6/kg was 3.4 (IQR:2.5-4.6) and 33% received G-CSF post-ASCT. A total of 13% received consolidation and 8% maintenance treatment post-ASCT. The median follow-up post-ASCT was 84 months (IQR:46-122). The median time to neutrophil engraftment was 12 days (IQR:11-13) and to platelet engraftment 13 days (11-16). The best hematological response at Day +100 post-ASCT (33% missing) was as follows: CR 44%, VGPR 26% and PR 29%. Mean eGFR at auto-HCT was 48.8 mL/min/1.73m 2 (95% CI 36.8-60.8) in those not on dialysis and 15.2 mL/min/1.73m 2 (95% CI 1.9-28.8) in those on dialysis (difference 33.6 mL/min/1.73m 2, p<0.0001). In both groups there were no significant changes in eGFR after auto-HCT (p=0.99 and p=0.80, respectively). The box-plot figure shows eGFR at auto-HCT, and at 3, 6 and 12 months. At 6 years post-ASCT, OS was 88% (95% CI: 78-98%) and PFS was 44% (95% CI 28-60%). The median OS was not reached. The median PFS was 65 months (95% CI: 45-103). The 2-year cumulative relapse incidence was 17% (95% CI: 6-27%) and the 2-year cumulative incidence of NRM was 2% (95% CI: 0-6%). In univariate analysis, transplant from 2012 onwards was associated with a significantly superior OS (6-year OS 100 vs. 75%; log-rank p=0.05). There was a trend to superior OS in females (6-year OS 100 vs 82%, p=0.05). There was no significant association between KPS, Age, Disease Status at ASCT (VGPR or better vs. Other) or Dialysis Status at ASCT with any outcomes in this small cohort evaluation. Conclusions: ASCT is a feasible option for patients with LCDD even though 42% were on dialysis at the time of transplantation. Overall outcomes are favourable with a low NRM and good long-term OS. There was no improvement in renal function.

Disease Characteristics and Outcomes of 504 Young Patients Diagnosed with Multiple Myeloma Treated with Modern Therapies in Canada

Background:Multiple myeloma (MM) mostly affects older adults. Although representing around 10% of all cases, patients ≤ 50 years old suffer from the highest number of years lost due to their disease. MM in young patients occurs during their most productive years of life, resulting in a significantly higher personal, familial, professional, and economic burden. Young MM patients are currently underrepresented in clinical trials due to small numbers overshadowed in cohorts of older patients. Their disease characteristics and outcomes following modern treatments remain poorly understood (Tanguay M et al., Current Oncol 2023). The purpose of this study is to report disease characteristics, treatments, and outcomes of young MM patients treated in Canada. Methods:This is a retrospective study using the Canadian Myeloma Research Group Database, which is a repository of real-world patient data reflecting 17 of the major MM academic centers across Canada. All patients 18-50 years old with newly diagnosed MM between January 1, 2010 and July 1, 2022 were included. High-risk (HR) cytogenetics were defined as either del17p, t(4;14) or t(14;16). Survival analyses were performed using the Kaplan-Meier method. Results:Among the 6,604 patients newly diagnosed with MM during the study period, 504 (7.6%) were aged between 18-50 years, and included in this analysis. Within this young group, 87 (17.3%) were 18-40 years old and 417 (82.7%) were between 41-50 years. MM was diagnosed in 301 (59.7%) patients between 2010 to 2015, and in 203 (40.3%) patients between 2016 to 2022. The median age at diagnosis was 45.9 years (range 25.6 to 50). Male patients represented 57.7% of the cohort. IgG was the most common isotype in 251 (49.8%) cases, while 115 (22.8%) patients had light chain disease. In 375 patients with available data, 16% were R-ISS 1, 73.1% R-ISS 2, and 10.9% R-ISS 3. Lytic lesions, elevated creatinine, anemia, hypercalcemia, and high LDH were respectively present in 46.8%, 15.5%, 44%, 18.8%, and 18.7% of patients. HR cytogenetics were present in 23.7% of patients, with del17p in 11.5%, t(4;14) in 14.9%, and t(14;16) in 5.1%; while 1q+ and del1p were detected in 27.9% and 15.3%, respectively. Twelve (2.4%) patients were diagnosed with plasma cell leukemia. First-line treatment was proteasome inhibitor (PI)-based in 462 (91.7 %) and immunomodulatory (IMiD) agent-based in 7 (1.4 %); 18 (3.6%) received both a PI and an IMiD and 17 (3.4%) were treated with other modalities. Among all patients, 453 (89.9%) underwent autologous stem cell transplant (ASCT) during their disease course. Some patients did not receive ASCT for the following reasons: early death before ASCT in 10 (2%) cases, lost to follow-up prior to ASCT in 13 (2.6%) cases, deemed ineligible for ASCT or patient declined in 24 (4.8%) cases, and participation in a clinical trial not involving ASCT in 1 (0.2%) case. Out of the entire cohort, allogeneic-SCT (allo-SCT) was performed in only 11 patients (2.2%), including 3 (0.6%) who received allo-SCT alone without ASCT. Among patients who received maintenance post ASCT, 93.6% were treated with a lenalidomide-based regimen. Median duration of the different maintenance treatments was 21.2 months. With a median follow-up of 51.9 months (range 0.9 to 154), median PFS (progression-free survival) was 55.4 months (95% CI 49.1-70.2), while median OS (overall survival) was not reached. The 5-year OS and PFS were 78% (95% CI 74-82) and 48% (95% CI 43-53), respectively, whereas the 10-year OS and PFS were 64% (95% CI 58-71) and 28% (95% CI 22-35), respectively (Figure 1a). Median PFS for patients with any HR cytogenetics was 37.9 months (95% CI 29.6-62.8) vs 64.5 months (95% CI 50.6-80.7) for patients with standard-risk cytogenetics (p=0.004) (Figure 1b). We observed no difference in disease characteristics, treatments, and outcomes after comparing cohorts aged 18-40 years old vs 41-50 years old. Conclusions: This is among the largest real-world cohorts of young MM patients ≤ 50 years old treated with modern therapies ever reported. Most patients were R-ISS 2 (73.1%), 23.7% had known HR cytogenetics, and the majority (91.7%) received a PI-based first-line treatment. Outcomes of specific subgroups are under analysis and will be presented. Although the OS was not yet reached in this young population, the median PFS of only 55.4 months highlights the urgent need to develop more effective treatments to induce deeper and more durable responses.

Young and Distinct: Clinical Characteristics and Outcomes of Patients 50 or Younger with Multiple Myeloma

Introduction: Multiple Myeloma (MM) presents at a median age of 69. Patients age 50 or younger represent only 10% of diagnoses and are less well-characterized. Some studies have suggested that younger MM patients are more likely to present with lytic lesions, be IgD subtype, have high-risk cytogenetics, and have relatively improved survival. We aimed to characterize this understudied population in the modern era. Methods: We conducted a retrospective chart review of patients age <50 meeting IMWG criteria for symptomatic MM treated across our institution's cancer center network between 2010 and 2023. Overall survival was defined as time in months from diagnosis to last follow-up or death. Time to relapse after transplant was captured. Results: We identified 97 younger MM patients, with a median age of 44 (range 26-50). Males and females represented 50.5% and 49.5% of cases respectively. Complete demographics are listed in the table. The most common MM subtype was IgG Kappa (40%), and 23% had light chain-only disease. Incidentally found cases, defined as abnormalities on imaging or labs ordered for another reason, represented 11% of cases. 61% of patients presented with a skeletal issue such as bone pain and/or pathologic fracture. Presenting features are described in the table. At time of diagnosis, 77% of patients were found to have lytic lesions. Few patients had previously identified MGUS (3%) or smoldering MM (5%). Regarding cytogenetics, 18% had one or more high-risk features. The most common frontline treatment was VRD. As shown in the table, 66% and 29% received 3 and 4 drug induction regimens respectively. Of note, 91% were referred for autologous stem cell transplant (ASCT), and 72% proceeded. 4 patients were deceased at the time of analysis. Survival for the entire population was 95.9% at a median follow up time of 65.5 months. In the patients who underwent ASCT, 41.2% relapsed with median progression-free survival of 57 (44-71) months. Conclusions: MM patients age <50 were found to be distinct from the known characteristics of the general population in several notable ways. There was equipoise among demographic features, with a nearly equivalent prevalence in males and females, and similar median ages across racial groups. We found a greater enrichment of light chain disease than expected, but less renal dysfunction at presentation. IgD subtype does not appear increased in this population. Younger patients do not appear more likely to have high risk cytogenetics. Lastly, survival for younger patients was higher compared to the reported 5-year survival of MM, which may be explained by the finding that these patients were treated primarily with triplet or quadruplet anti-myeloma regimens and often proceeded to ASCT.

A Case of Combined Light Chain Deposition Disease and Light Chain Cast Nephropathy

A Case of Combined Light Chain Deposition Disease and Light Chain Cast Nephropathy

Primary Plasma Cell Leukaemia with Lambda Light Chain secretion and Chromosomal abnormalities presenting as hyperleukocytosis - A case report.

Primary plasma cell leukaemia (pPCL) is a rare and lethal form of plasma cell dyscrasia that can occur either de novo (primary) or as a leukemic transformation of refractory or relapsed multiple myeloma. We report a case of pPCL with lambda light chain disease and multiple chromosomal abnormalities in a 75-year-old female who presented with generalized weakness. Her peripheral blood smear showed hyperleukocytosis with 78% circulating plasma cells. Serum protein electrophoresis (SPE) does not reveal the M band and serum immunofixation (SI) light chain analysis in serum showed an elevated lambda light chain. Skeletal radiography and PET-CT (positron emission tomography—computerized tomography) did not reveal any lytic lesions. Immunophenotypic studies reveal a CD38-positive population with negativity for T cells, B cells, myeloid markers, and a negative CD45. Fluorescent in situ hybridization (FISH) analysis results disclosed the deletion of 13q14.3 and t(11; 14). This case highlighted the usefulness of the peripheral smear findings and high fluorescent lymphocyte activity, which directed the pathologist to initiate workup for pPCL, and comprehensive laboratory biochemical and radiological evaluation further helps to confirm and differentiate pPCL from multiple myeloma. Bangladesh Journal of Medical Science Vol. 22 No. 04 October’23 Page : 932-936

Coinciding kappa AL amyloidosis and kappa light chain deposition disease in the lung.

Coinciding kappa AL amyloidosis and kappa light chain deposition disease in the lung.

Treatment and Outcome of Light Chain Deposition Disease in the Era of Novel Agents and Transplant.

Treatment and Outcome of Light Chain Deposition Disease in the Era of Novel Agents and Transplant.

Role of the mechanisms for antibody repertoire diversification in monoclonal light chain deposition disorders: when a friend becomes foe.

The adaptive immune system of jawed vertebrates generates a highly diverse repertoire of antibodies to meet the antigenic challenges of a constantly evolving biological ecosystem. Most of the diversity is generated by two mechanisms: V(D)J gene recombination and somatic hypermutation (SHM). SHM introduces changes in the variable domain of antibodies, mostly in the regions that form the paratope, yielding antibodies with higher antigen binding affinity. However, antigen recognition is only possible if the antibody folds into a stable functional conformation. Therefore, a key force determining the survival of B cell clones undergoing somatic hypermutation is the ability of the mutated heavy and light chains to efficiently fold and assemble into a functional antibody. The antibody is the structural context where the selection of the somatic mutations occurs, and where both the heavy and light chains benefit from protective mechanisms that counteract the potentially deleterious impact of the changes. However, in patients with monoclonal gammopathies, the proliferating plasma cell clone may overproduce the light chain, which is then secreted into the bloodstream. This places the light chain out of the protective context provided by the quaternary structure of the antibody, increasing the risk of misfolding and aggregation due to destabilizing somatic mutations. Light chain-derived (AL) amyloidosis, light chain deposition disease (LCDD), Fanconi syndrome, and myeloma (cast) nephropathy are a diverse group of diseases derived from the pathologic aggregation of light chains, in which somatic mutations are recognized to play a role. In this review, we address the mechanisms by which somatic mutations promote the misfolding and pathological aggregation of the light chains, with an emphasis on AL amyloidosis. We also analyze the contribution of the variable domain (VL) gene segments and somatic mutations on light chain cytotoxicity, organ tropism, and structure of the AL fibrils. Finally, we analyze the most recent advances in the development of computational algorithms to predict the role of somatic mutations in the cardiotoxicity of amyloidogenic light chains and discuss the challenges and perspectives that this approach faces.

New Onset Nephrotic - Range Proteinuria in a Patient with Chronic Kidney Disease - Not Always What it Seems

Light chain deposition disease (LCDD) is a rare condition that is characterized by the deposition of monoclonal immunoglobulin light chains in glomerular and tubular basement membranes. We report the case of a 72-year-old male with long-standing and stable chronic kidney disease (CKD) presumably due to hypertension.

Light and heavy chain deposition disease with focal amyloid deposition diagnosed with mass spectrometry: a case report

BackgroundLight and heavy chain deposition disease (LHCDD) is a rare condition characterised by the deposition of immunoglobulin components in the kidneys. Similarly, Amyloidosis is also caused by the deposition of light chain and/or heavy chain components of immunoglobulins which are folded into amyloid fibrils characterised by Congophilic deposits that exhibit apple-green birefringence under polarised light. Only a handful of reports describing LHCDD with amyloid fibril deposition have been previously published, however, none have characterized the composition of the deposited immunoglobulin components via mass spectrometry.Case presentationWe report a case of a 79-year-old Japanese woman with nephrotic syndrome. Bone marrow aspiration revealed a slight proliferation of plasma cells (under 10%). Immunofluorescence assessment of renal biopsy showed amyloid-like deposits in the glomerulus that were positive for IgA and kappa. Further, the Congo red staining of the deposits was faintly positive, and only a slight birefringence was detected. Electron microscopy confirmed fine fibrillar structures and non-amyloid deposits. Finally, mass spectrometry revealed that the deposits were composed of abundant amounts of light chain with small amounts of heavy chain. Therefore, the patient was diagnosed with LHCDD and focal amyloid deposition. Chemotherapy was subsequently initiated, which resulted in haematological and renal response. Under polarised light, faint birefringence with Congo red staining and periodic acid-methenamine silver positivity indicated that the deposits were mostly non-amyloid fibrils with a small component of amyloid fibrils. Generally, the diagnosis of heavy- and light-chain amyloidosis is defined by greater heavy chain deposition compared to the light chain. However, in our case, contrary to the definition, the light-chain deposition was far greater than that of the heavy-chain.ConclusionsThis is the first case of LHCDD with focal amyloid deposition diagnosed by analysing the glomerular deposits by mass spectrometry.

Cardiac events after standard of care idecabtagene vicleucel for relapsed and refractory multiple myeloma

AbstractIdecabtagene vicleucel (ide-cel) is a type of B-cell maturation antigen (BCMA)–targeting chimeric antigen receptor T-cell (CAR-T) approved for the treatment of relapsed and refractory multiple myeloma (RRMM). Currently, the incidence of cardiac events associated with ide-cel remains unclear. This was a retrospective single-center observational study of patients treated with ide-cel for RRMM. We included all consecutive patients who received standard-of-care ide-cel treatment at least 1-month follow-up. Baseline clinical risk factors, safety profile, and responses were examined based on the development of a cardiac event. A total of 78 patients were treated with ide-cel, and 11 patients (14.1%) developed cardiac events: heart failure (5.1%), atrial fibrillation (10.3%), nonsustained ventricular tachycardia (3.8%), and cardiovascular death (1.3%). Only 11 of the 78 patients had repeat echocardiogram. Baseline risk factors associated with the development of cardiac events included being female sex and having poor performance status, λ light-chain disease, and advanced Revised International Staging System stage. Baseline cardiac characteristics were not associated with cardiac events. During index hospitalization after CAR-T, higher-grade (≥grade 2) cytokine release syndrome (CRS) and immune cell–associated neurologic syndrome were associated with cardiac events. In multivariable analyses, the hazard ratio for the association of the presence of cardiac events with overall survival (OS) was 2.66 and progression-free survival (PFS) was 1.98. Ide-cel CAR-T for RRMM was associated with similar cardiac events as other types of CAR-T. Worse baseline performance status and higher-grade CRS and neurotoxicity were associated with cardiac events after BCMA-directed CAR-T-cell therapy. Our results suggest that the presence of cardiac events may confer worse PFS or OS; although because of the small sample size, the power to detect an association was limited.

#3597 MONOCLONAL GAMMOPATHY AS A RISK FACTOR FOR ARTERIOVENOUS FISTULA PRIMARY FAILURE

Abstract Background and Aims Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis (HD) in most patients. However, postoperative complications such as primary failure (PF) with a reported incidence between 20-60% remain a major problem. Patients diagnosed with monoclonal gammopathy (MG) are at increased risk of thrombotic events, either due to the disease itself or the chemotherapy used for its treatment. The aim of this study was to evaluate whether the presence of MG was associated with primary AVF failure. Method We performed a retrospective single-center case-control study including 103 patients observed in our vascular access consultation for planning their first HD access. Demographic and clinical data were collected, such as the presence of diabetes, hypertension, cardiovascular disease and MG. Distal AVF was the access of choice when possible. Primary failure was defined as incapacity to use AVF for HD because of failure to mature or thrombosis. Univariate analysis was performed, and a logistic regression was applied to access predictors of PF. A p-value inferior to 0,05 indicated statistical significance. Results In total 14 (13.6%) patients had MG (11 multiple myeloma, 1 light-chain deposition disease, 1 proliferative glomerulonephritis with monoclonal immunoglobulin deposits and 1 amyloid light-chain amyloidosis). Regarding the AVF location, 13 patients constructed a constructed a distal AVF and 1 patient a proximal AVF. When compared to the group of 89 patients who did not have MG, there were no significance differences in sex, age, prevalence of diabetes and cardiovascular disease neither in AVF construction site. Arterial hypertension was more frequent in the group of patients without MG (93.2% versus 64.3%, p = 0.007). PF occurred in 57.1% (8/14) of patients with MG and in 27% (24/89) of those without MG (p = 0.032). In logistic regression, the presence of MG was the only predictor of primary AVF failure (OR 4.39 95% CI: 1.23-15.75). Conclusion In our study, we found that a patient with monoclonal gammopathy has a 4-fold increased risk for primary AVF failure comparing to the general chronic kidney disease patients. Therefore, a careful evaluation must be made when planning for AVF placement in these patients, balancing individual life's expectancies and monoclonal gammopathy prognosis.

Renal Disorders Associated with Waldenström Macroglobulinaemia, IgM MGUS and IgM-Producing B-Cell Lymphoproliferative Disorders

Renal disorders are uncommonly associated with IgM MGUS and Waldenström macroglobulinaemia (WM). Data are limited to large case series that suggest that related renal involvement occurs in 5% of patients with WM. Although uncommon, there is a much greater variety of renal pathologies associated with WM and IgM MGUS than that seen in patients with multiple myeloma, where cast nephropathy predominates. In WM, uncommonly direct infiltration of the renal system by lymphoma or cast nephropathy with a high light-chain level can occur. AL amyloidosis can present with nephrotic syndrome as a feature with IgM MGUS or WM. Cryoglobulinaemia and light-chain deposition disease are other important potential causes of renal impairment with IgM MGUS and WM. There are other rarer monoclonal gammopathy of renal significance (MGRS) conditions characterised by typically isolated kidney disease that are causally related to a B-cell or plasma-cell clonal disorder usually in a precancerous MGUS state, although in some renal pathologies, the association is less clear. Central to the majority of these diagnoses is the need for an accurate renal histological diagnosis, and management requires close joint working of renal and haematology teams.

#5788 MONOCLONAL GAMMOPATHY OF RENAL SIGNIFICANCE: A SINGLE CENTER EXPERIENCE

Abstract Background and Aims Monoclonal gammopathy of renal significance is an organ-threatening manifestation of paraproteinemia. It can be secondary to the clonal proliferation of either plasma cells or mature B-lymphocytes. The underlying clonal disorder does not meet the current hematologic criteria for immediate myeloma-specific therapy. With the advent of routine use of light chain detection by immunofluroscence technique in tissue biopsy, more cases of monoclonal gammopathy of renal significance are being diagnosed but there remains a therapeutic uncertainty. Data regarding the prognosis and outcomes of the various clinical manifestations of monoclonal gammopathy of renal significance is limited due to its rarity and under diagnosis. MGRS if left untreated can lead to end-stage renal disease and premature death. Method This is a retrospective study conducted at the Institute of Nephro-urology, Bangalore by retrieving the data from the digital medical records of our institute. Demographic and clinical details of the patients diagnosed with monoclonal gammopathy of renal significance from 1 st January 2018 to 31 st October 2022 were collected. Myeloma related light chain cast nephropathy was excluded from the study. Follow-up data were collected usingout patient data base, through telephone, and from the records at the cancer institute where the patient was referred post-diagnosis at our institute. The data collected was entered in excel and analyzed using SPSS software version 27.0. Results Fifty eight patients (n = 52) were diagnosed with the disease during the study period. MGRS contributed to 1.27% of all the renal biopsies conducted at our institute during the study period. The mean age of the study population was 52.1 with 95% CI [48.5 to 55.6] with a male: female ratio of 1.36:1 and 36.5% (n = 19) ofstudy cohort aged above 60 years. Among clinical presentations CKD (n = 23) was the main clinical presentation followed by AKI, Nephrotic syndrome, Nephritic syndrome and RPGN as the other presentations. Dialysis requirement was noted in 35% at initial presentation. Most common histiopathological presentation was Amyloidosis (n = 15) followed by Light chain deposition disease LCDD (n = 14), monoclonal non-amyloid deposition disease NADD (n = 6), Light chain proximal tubulopathy LCPT (n = 5), Proliferative glomerulonephritis with monoclonal immunoglobulin deposition disease PGNMIDD (n = 9) and others (n = 3). The patient survival at the time of analysis was 22.7% and death censored renal survival was 80%. Conclusion MGRS contributed to 1.27% of all the renal biopsies conducted at our institute during the study period. Because of its variable clincal presentation,one needs high degree of clinical suspicion for early diagnosis. MGRS unlike MGUS carries significant morbidity and mortality.

Multiple Facets of Multiple Myeloma in Kidney Biopsy: A Multicenter Retrospective Study.

Multiple myeloma is a type of plasma cell dyscrasia, which causes clonal proliferation of plasma cells and deposition in various organ systems. At presentation, 50% of patients with multiple myeloma have kidney dysfunction, which is considered a poor prognostic indicator. Data on the histopathological manifestations of multiple myeloma are sparse. To look at the kidney histopathological lesions in patients with the clinical diagnosis of multiple myeloma. A retrospective analysis of all kidney biopsies in patients with the clinical diagnosis of multiple myeloma was performed from June 1, 2020 to May 30, 2022, from three tertiary care nephrology referral centers. A total of 61 patients with multiple myeloma and biopsy-proven kidney involvement were included in the study. The mean age at presentation was 55.39 ± 11.91 years, with male predominance (male to female ratio -1.6:1). The most common lesion on kidney biopsy was myeloma cast nephropathy (72.1%), followed by light chain deposition disease (21.3%) and AL amyloidosis (18%). About 26% of patients had dual lesions on kidney biopsy, 3% had three types of lesions on kidney biopsy In 48% of patients, the diagnosis of multiple myeloma was made only after the kidney biopsy. Patients with multiple myeloma and kidney involvement should be biopsied as the type of histopathological lesion influences the treatment options and prognosis.

Prevalence of MGCS Among Patients With Monoclonal Gammopathies.

Prevalence of MGCS Among Patients With Monoclonal Gammopathies.

Light chain deposition disease: spotlight on a rare cutaneous disease.

Light chain deposition disease: spotlight on a rare cutaneous disease.

Intrapleural findings of pulmonary light-chain deposition disease.

Light-chain deposition disease is accompanied not only by characteristic CT findings but also by characteristic gross findings of the visceral pleura. Medical thoracoscopy could diagnose LCDD by the findings of the thoracic cavity.

Immunophenotypic expression profile of multiple myeloma cases at a tertiary hospital in Nairobi Kenya.

Multiple myeloma (MM) is a plasma cell neoplasm that constitutes 10-15% of all hematopoietic neoplasms. Kenya is placed among the top five African countries for MM incidence and MM-related mortality. Prior studies have suggested that the aberrant expression of Cyclin D1, CD56, CD117 and Ki-67 on neoplastic plasma cells is useful in disease prognostication. The prevalence and significance of expression of these markers in a cohort of MM cases in Kenya has not been studied previously. A retrospective cross-sectional study was carried out at the Aga Khan University Hospital, Nairobi. The study population included 83 MM cases with available trephine blocks archived between 1st of January 2009 and 31st of March 2020. Immunohistochemical expression of Cyclin D1, CD56, CD117, and Ki-67 was analyzed and scored. The biomarkers were described using frequencies based on the positive and negative results. Fisher's exact test was used to determine the association between the immunophenotypic markers and categorical variables. Of the 83 selected cases, expression of Cyclin D1, CD56, CD117 and Ki-67 was identified in 28.9, 34.9, 7.2, and 50.6%, respectively. Cyclin D1 positivity was significantly associated with hypercalcemia. Absence of CD117 expression was noted to be associated with adverse risk parameters including an IgA isotype or light chain disease, International Staging System (ISS) stage III disease, abnormal baseline serum free light chains (sFLC) and a high plasma cell burden. Cyclin D1 expression was congruent with previously reported studies. The frequency of CD56 and CD117 expression was lower than previously reported. This may be due to differences in disease biology between the study populations. Approximately half of cases were Ki-67 positive. Our data showed limited associations between the expression of studied markers and clinicopathologic variables. However, this could be attributed to the small study sample size. We would recommend further characterization of the disease in a larger prospective study with the inclusion of survival outcomes and cytogenetic studies.