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Journal of Nippon Medical School =... 2019Abnormal proliferation of plasma cells and some monoclonal B cells frequently cause the secretion of monoclonal immunoglobulins or immunoglobulin fragments into the... (Review)
Review
Abnormal proliferation of plasma cells and some monoclonal B cells frequently cause the secretion of monoclonal immunoglobulins or immunoglobulin fragments into the serum, causing monoclonal gammopathy, which leads to various diseases including renal diseases. Therefore, monoclonal gammopathy is frequently associated with kidney diseases, including glomerular and tubulointerstitial diseases. Glomerular disease, with the deposition of monoclonal immunoglobulins or their components, includes monoclonal immunoglobulin deposition disease (MIDD), AL or AH amyloidosis, type I cryoglobulinemia, proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID), immunotactoid glomerulopathy, and fibrillary glomerulonephritis. In addition, tubulointerstitial diseases with the deposition of monoclonal immunoglobulins or their components are constituted by light chain (myeloma) cast nephropathy, light chain associated Fanconi's syndrome (light chain proximal [crystal] tubulopathy), and crystal-storing histiocytosis. In the present review article, we demonstrate the clinicopathological characteristics of MIDD, which is one of the representative diseases of plasma cell dyscrasias, and discuss various renal diseases with the deposition of monoclonal immunoglobulins or their components in glomeruli and the tubulointerstitium. We recommend that these renal diseases are arranged as one disease category, "renal diseases with deposition of monoclonal immunoglobulins or their components", in order to simplify the understanding of complicated diseases in plasma cell dysplasia.
Topics: Antibodies, Monoclonal; Cryoglobulinemia; Fanconi Syndrome; Glomerulonephritis; Histiocytosis; Humans; Immunoglobulin G; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; Paraproteinemias
PubMed: 30918151
DOI: 10.1272/jnms.JNMS.2019_86-1 -
Blood Cancer Journal Sep 2022Smoldering multiple myeloma (SMM) is an asymptomatic condition that occupies a space between monoclonal gammopathy of undetermined significance (MGUS) and multiple... (Review)
Review
Smoldering multiple myeloma (SMM) is an asymptomatic condition that occupies a space between monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) along the spectrum of clonal plasma cell proliferative disorders. It is not a biologic intermediate stage between MGUS and MM, but rather represents a heterogeneous clinically defined condition in which some patients (approximately two-thirds) have MGUS (pre-malignancy), and some (approximately one-third) have MM (biologic malignancy). Unfortunately, no single pathologic or molecular feature can reliably distinguish these two groups of patients. For purposes of practice and clinical trials, specific risk factors are used to identify patients with SMM in whom malignant transformation has already likely occurred (high risk SMM). Patients with newly diagnosed high risk SMM should be offered therapy with lenalidomide or lenalidomide plus dexamethasone (Rd) for 2 years, or enrollment in clinical trials. Patients with low risk SMM should be observed without therapy every 3-4 months.
Topics: Algorithms; Biological Products; Disease Progression; Humans; Lenalidomide; Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Paraproteinemias; Smoldering Multiple Myeloma
PubMed: 36064707
DOI: 10.1038/s41408-022-00719-0 -
Virchows Archiv : An International... Jan 2023Plasma cell neoplasms including multiple myeloma (MM) and related terminally differentiated B-cell neoplasms are characterized by secretion of monoclonal immunoglobulin... (Review)
Review
Plasma cell neoplasms including multiple myeloma (MM) and related terminally differentiated B-cell neoplasms are characterized by secretion of monoclonal immunoglobulin and stepwise development from a preneoplastic clonal B and/or plasma cell proliferation called monoclonal gammopathy of undetermined significance (MGUS). Diagnosis of these disorders requires integration of clinical, laboratory, and morphological features. While their classification mostly remains unchanged compared to the revised 2016 WHO classification and the 2014 International Myeloma Working Group consensus, some changes in criteria and terminology were proposed in the 2022 International Consensus Classification (ICC) of mature lymphoid neoplasms. MGUS of IgM type is now divided into IgM MGUS of plasma cell type, precursor to the rare IgM MM and characterized by MM-type cytogenetics, lack of clonal B-cells and absence of MYD88 mutation, and IgM MGUS, NOS including the remaining cases. Primary cold agglutinin disease is recognized as a new entity. MM is now formally subdivided into cytogenetic groups, recognizing the importance of genetics for clinical features and prognosis. MM with recurrent genetic abnormalities includes MM with CCND family translocations, MM with MAF family translocations, MM with NSD2 translocation, and MM with hyperdiploidy, with the remaining cases classified as MM, NOS. For diagnosis of localized plasma cell tumors, solitary plasmacytoma of bone, and primary extraosseous plasmacytoma, the importance of excluding minimal bone marrow infiltration by flow cytometry is emphasized. Primary systemic amyloidosis is renamed immunoglobulin light chain amyloidosis (AL), and a localized AL amyloidosis is recognized as a distinct entity. This review summarizes the updates on plasma cell neoplasms and related entities proposed in the 2022 ICC. KEY POINTS: • Lymphoplasmacytic lymphoma can be diagnosed with lymphoplasmacytic aggregates in trephine biopsies < 10% of cellularity and evidence of clonal B-cells and plasma cells. • IgM MGUS is subdivided into a plasma cell type and a not otherwise specified (NOS) type. • Primary cold agglutinin disease is recognized as a new entity. • The term "multiple myeloma" replaces the term "plasma cell myeloma" used in the 2016 WHO classification. • Multiple myeloma is subdivided into 4 mutually exclusive cytogenetic groups and MM NOS. • Minimal bone marrow infiltration detected by flow cytometry is of major prognostic importance for solitary plasmacytoma of bone and to a lesser extent for primary extraosseous plasmacytoma. • Localized IG light chain amyloidosis is recognized as a separate entity, distinct from systemic immunoglobulin light chain (AL) amyloidosis.
Topics: Humans; Multiple Myeloma; Plasmacytoma; Paraproteinemias; Anemia, Hemolytic, Autoimmune; Monoclonal Gammopathy of Undetermined Significance; Amyloidosis; Lymphoma, B-Cell; Translocation, Genetic; Immunoglobulin M
PubMed: 36414803
DOI: 10.1007/s00428-022-03431-3 -
Leukemia May 2023Multiple Myeloma (MM) remains an incurable plasma cell neoplasm. Although little is known about the etiology of MM, several metabolic risk factors such as obesity,... (Review)
Review
Multiple Myeloma (MM) remains an incurable plasma cell neoplasm. Although little is known about the etiology of MM, several metabolic risk factors such as obesity, diabetes mellitus, diet, and the human intestinal microbiome have been linked to the pathogenesis of MM. In this article, we provide a detailed review of dietary and microbiome factors involved in the pathogenesis of MM and their impact on outcomes. Concurrent with treatment advancements that have improved survival in MM, focused efforts are needed to reduce the burden of MM as well as improve MM specific and overall outcomes once MM is diagnosed. The findings presented in this review will provide a comprehensive guide on the evidence available to date of the impact of dietary and other lifestyle interventions on the gut microbiome and on MM incidence, outcomes, and quality of life. Data generated from such studies can help formulate evidence-based guidelines for healthcare providers to counsel individuals at risk such as those with Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM) as well as MM survivors with respect to their dietary habits.
Topics: Humans; Multiple Myeloma; Plasma Cells; Quality of Life; Paraproteinemias; Diet; Microbiota
PubMed: 36997677
DOI: 10.1038/s41375-023-01874-4 -
Oncotarget Apr 2023Systemic Light chain (AL) amyloidosis is a monoclonal plasma cell proliferative disorder characterized by deposition of amyloidogenic monoclonal light chain fragments... (Review)
Review
Systemic Light chain (AL) amyloidosis is a monoclonal plasma cell proliferative disorder characterized by deposition of amyloidogenic monoclonal light chain fragments causing organ dysfunction. It is a fatal disease and if not diagnosed and treated early can lead to organ failure and potentially death. The renal system along with the cardiovascular system are the most common organs involved but other organs such as gut and liver can be involved as well. The initial evaluation of patients requires confirming the diagnosis with tissue biopsy and staining with Congo red followed by confirmatory typing with mass spectrometry of the Congo red positive tissue. Then establishing the extent of the organs involvement by various staging and biomarkers testing. The treatment options and the tolerability of therapy depend on the disease staging, frailty, and co-morbidities. The autologous hematopoietic cell transplantation (HCT) after high dose melphalan therapy is an effective strategy which is usually done after initial bortezomib induction therapy. Unfortunately, most systemic AL amyloidosis patients are not candidate for HCT due to frailty, old age, multi-organ involvement, renal and heart failure at the time of diagnosis. While it is widely accepted that the patients need to be treated until they achieve complete hematologic response, the maintenance therapy after HCT is not well established in AL amyloidosis. In this review, we report the literature on the latest treatment updates of AL amyloidosis and the ongoing clinical trials highlighting the future treatments.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Congo Red; Frailty; Melphalan; Hematopoietic Stem Cell Transplantation; Paraproteinemias
PubMed: 37185672
DOI: 10.18632/oncotarget.28415 -
Journal of the American Society of... Jul 2018Monoclonal gammopathies are characterized by the overproduction of monoclonal Ig (MIg) detectable in the serum or urine resulting from a clonal proliferation of plasma... (Review)
Review
Monoclonal gammopathies are characterized by the overproduction of monoclonal Ig (MIg) detectable in the serum or urine resulting from a clonal proliferation of plasma cells or B lymphocytes. The underlying hematologic conditions range from malignant neoplasms of plasma cells or B lymphocytes, including multiple myeloma and B-cell lymphoproliferative disorders, to nonmalignant small clonal proliferations. The term MGUS implies presence of an MIg in the setting of a "benign" hematologic condition without renal or other end organ damage. The term MGRS was recently introduced to indicate monoclonal gammopathy with MIg-associated renal disease in the absence of hematologic malignancy. Most MIg-associated renal diseases result from the direct deposition of nephrotoxic MIg or its light- or heavy-chain fragments in various renal tissue compartments. Immunofluorescence microscopy is essential to identify the offending MIg and define its tissue distribution. Mass spectrometry is helpful in difficult cases. Conditions caused by direct tissue deposition of MIg include common disorders, such as cast nephropathy, amyloidosis, and MIg deposition diseases, as well as uncommon disorders, such as immunotactoid glomerulopathy, proliferative GN with MIg deposits, light-chain proximal tubulopathy, and the rare entities of crystal-storing histiocytosis and crystalglobulinemia. Indirect mechanisms of MIg-induced renal disease can cause C3 glomerulopathy or thrombotic microangiopathy without tissue MIg deposits. Treatment of MIg-associated renal disease is aimed at eliminating the clonal plasma cell or B-cell population as appropriate. Both the renal and the underlying hematologic disorders influence the management and prognosis of MIg-associated renal diseases.
Topics: Amyloidosis; Humans; Immunoglobulin Heavy Chains; Immunoglobulin Light Chains; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; Laser Capture Microdissection; Mass Spectrometry; Paraproteinemias; Terminology as Topic
PubMed: 29703839
DOI: 10.1681/ASN.2017121319 -
Blood Oct 2018Monoclonal gammopathy is a common condition, particularly in the elderly. It can indicate symptomatic multiple myeloma or another overt malignant lymphoid disorder... (Review)
Review
Monoclonal gammopathy is a common condition, particularly in the elderly. It can indicate symptomatic multiple myeloma or another overt malignant lymphoid disorder requiring immediate chemotherapy. More frequently, it results from a small and/or quiescent secreting B-cell clone, is completely asymptomatic, and requires regular monitoring only, defining a monoclonal gammopathy of unknown significance (MGUS). Sometimes, although quiescent and not requiring any treatment per se, the clone is associated with potentially severe organ damage due to the toxicity of the monoclonal immunoglobulin or to other mechanisms. The latter situation is increasingly observed but still poorly recognized and frequently undertreated, although it often requires rapid specific intervention to preserve involved organ function. To improve early recognition and management of these small B-cell clone-related disorders, we propose to introduce the concept of monoclonal gammopathy of clinical significance (MGCS). This report identifies the spectrum of MGCSs that are classified according to mechanisms of tissue injury. It highlights the diversity of these disorders for which diagnosis and treatment are often challenging in clinical practice and require a multidisciplinary approach. Principles of management, including main diagnostic and therapeutic procedures, are also described. Importantly, efficient control of the underlying B-cell clone usually results in organ improvement. Currently, it relies mainly on chemotherapy and other anti-B-cell/plasma cell agents, which should aim at rapidly producing the best hematological response.
Topics: Animals; Autoantibodies; B-Lymphocytes; Cytokines; Humans; Immunoglobulins; Paraproteinemias
PubMed: 30012636
DOI: 10.1182/blood-2018-04-839480 -
Blood Cancer Journal May 2022Multiple myeloma (MM) is an acquired malignant plasma cell disorder that develops late in life. Although progression free and overall survival has improved across all... (Review)
Review
Multiple myeloma (MM) is an acquired malignant plasma cell disorder that develops late in life. Although progression free and overall survival has improved across all age, race, and ethnic groups, a subset of patients have suboptimal outcomes and are labeled as having high risk disease. A uniform approach to risk in NDMM remains elusive despite several validated risk stratification systems in clinical use. While we attempt to capture risk at diagnosis, the reality is that many important prognostic characteristics remain ill-defined as some patients relapse early who were defined as low risk based on their genomic profile at diagnosis. It is critical to establish a definition of high risk disease in order to move towards risk-adapted treatment approaches. Defining risk at diagnosis is important to both effectively design future clinical trials and guide which clinical data is needed in routine practice. The goal of this review paper is to summarize and compare the various established risk stratification systems, go beyond the R-ISS and international myeloma working group risk stratifications to evaluate specific molecular and cytogenetic abnormalities and how they impact prognosis independently. In addition, we explore the wealth of new genomic information from recent whole genome/exome sequencing as well as gene expression data and review known clinical factors affecting outcome such as disease burden and early relapse as well as patient related factors such as race. Finally, we provide an outlook on developing a new high risk model system and how we might make sense of co-occurrences, oncogenic dependencies, and mutually exclusive mutations.
Topics: Humans; Multiple Myeloma; Neoplasm Recurrence, Local; Neoplasm Staging; Paraproteinemias; Prognosis
PubMed: 35637223
DOI: 10.1038/s41408-022-00679-5 -
Ugeskrift For Laeger Oct 2021Monoclonal gammopathies range from benign conditions to severe malignancies. A summary is given in this review. Overall, the prevalence is high; monoclonal gammopathies... (Review)
Review
Monoclonal gammopathies range from benign conditions to severe malignancies. A summary is given in this review. Overall, the prevalence is high; monoclonal gammopathies (MGUS) occur in > 3% of persons above 50 years of age. Approximately 400 new cases of multiple myeloma and 80 new cases of amyloid light-chain (AL) amyloidosis are diagnosed yearly in Denmark. MGUS is most often asymptomatic, but M-protein associated syndromes exist and should be considered when finding M-protein. Serum free light kappa and lambda chain analysis, CT, PET/CT and whole-body MRI have revolutionised diagnostics and monitoring of monoclonal gammopathies. New treatment modalities have improved outcome in multiple myeloma and AL amyloidosis.
Topics: Humans; Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Paraproteinemias; Positron Emission Tomography Computed Tomography
PubMed: 34709161
DOI: No ID Found -
Journal of the American Society of... May 2021Treatment of proliferative GN with monoclonal Ig deposits (PGNMID) is not established. A monoclonal anti-CD38 antibody (daratumumab) is effective in treating multiple...
BACKGROUND
Treatment of proliferative GN with monoclonal Ig deposits (PGNMID) is not established. A monoclonal anti-CD38 antibody (daratumumab) is effective in treating multiple myeloma. Abnormal plasma cell clones may play a role in the pathogenesis of PGNMID.
METHODS
We evaluated daratumumab's safety and efficacy in an open-label, phase 2 trial in 11 adults with PGNMID and one with C3 glomerulopathy (C3G) with monoclonal gammopathy. Patients had an eGFR >20 ml/min per 1.73 m and proteinuria >1 g/d. They received daratumumab intravenously (16 mg/kg) once weekly for 8 weeks, and then every other week for eight additional doses. Primary outcome was safety, defined as major infections, grade 3 or 4 anemia, leukopenia, or thrombocytopenia. Secondary outcomes were rate of complete remission (proteinuria <500 mg/d with <15% decline in baseline eGFR) or partial remission (>50% reduction in 24-hour proteinuria with <30% decline in eGFR) and proteinuria at 6 and 12 months.
RESULTS
One patient with C3G had GN unrelated to the monoclonal gammopathy, and one with PGNMID did not complete the first infusion. Five serious adverse events occurred. During the 12 months of the trial, six of the ten patients with PGNMID who received at least one dose of daratumumab had a partial response, and four had a complete response (an overall response rate of 100%). Three patients experienced relapse, two of whom re-entered partial remission after resuming daratumumab therapy. Proteinuria declined significantly, from a median of 4346 mg/d to 1264 mg/d by 12 months.
CONCLUSIONS
Daratumumab demonstrated an acceptable safety profile and resulted in significant improvement in proteinuria while stabilizing kidney function in patients with PGNMID, suggesting the drug merits further investigation.
CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER
Daratumumab in Treatment of PGNMID and C3 GN, NCT03095118.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antineoplastic Agents; Female; Glomerulonephritis, Membranoproliferative; Humans; Immunoglobulin G; Male; Middle Aged; Paraproteinemias; Pilot Projects; Treatment Outcome; Young Adult
PubMed: 33685975
DOI: 10.1681/ASN.2020101541