Plasma Cell Disorders

2015 ◽  
Author(s):  
Morie A. Gertz
Keyword(s):  
Multiple Myeloma ◽  
Black Women ◽  
Plasma Cell ◽  
Bone Disease ◽  
Monoclonal Gammopathy ◽  
White Women ◽  
Plasma Cells ◽  
The United States ◽  
Lytic Lesion ◽  
Undetermined Significance

Multiple myeloma represents 1.4% of all new patients with cancer and will result in an estimated 11,090 deaths in 2014. It is twice as common in black men as in white men and 2.5 times more common in black women than in white women. Myeloma is the 14th most common cause of cancer in the United States, with a median age at diagnosis of 69 years. Multiple myeloma is defined by the presence of a clonal growth of plasma cells, usually in the bone marrow, but patients may also present with extramedullary disease. Anemia and bone disease are common in patients with multiple myeloma. Multiple myeloma cells display multiple genetic abnormalities, with no one specific genetic lesion common to a majority of patients. This module describes the immunologic profile of multiple myeloma and its diagnosis, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, plasmacytoma, plasma cell leukemia, the clinical presentation of multiple myeloma bone disease, anemia, renal impairment, hypercalcemia, and neurologic symptoms associated with multiple myeloma. Therapy for transplantation-eligible and non–transplantation-eligible patients, maintenance treatment for multiple myeloma, Waldenström macroglobulinemia, and amyloidosis are also discussed. Tables outline the risk of monoclonal gammopathy of undetermined significance evolution, the myeloma staging system, recommended diagnostic testing and uniform response criteria for myeloma, and commonly used regimens in the treatment of myeloma. Figures include a magnetic resonance image showing multiple plasmacytomas, tibial lytic lesion from myeloma, calvarial lytic lesions, a positron emission tomographic scan in a myeloma patient, and hyperviscosity causing retinal hemorrhages. This review contains 5 highly rendered figures, 5 tables, and 149 references.

Plasma Cell Disorders

2015 ◽  
Author(s):  
Morie A. Gertz
Keyword(s):  
Multiple Myeloma ◽  
Black Women ◽  
Plasma Cell ◽  
Bone Disease ◽  
Monoclonal Gammopathy ◽  
White Women ◽  
Plasma Cells ◽  
The United States ◽  
Lytic Lesion ◽  
Undetermined Significance

Multiple myeloma represents 1.4% of all new patients with cancer and will result in an estimated 11,090 deaths in 2014. It is twice as common in black men as in white men and 2.5 times more common in black women than in white women. Myeloma is the 14th most common cause of cancer in the United States, with a median age at diagnosis of 69 years. Multiple myeloma is defined by the presence of a clonal growth of plasma cells, usually in the bone marrow, but patients may also present with extramedullary disease. Anemia and bone disease are common in patients with multiple myeloma. Multiple myeloma cells display multiple genetic abnormalities, with no one specific genetic lesion common to a majority of patients. This module describes the immunologic profile of multiple myeloma and its diagnosis, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, plasmacytoma, plasma cell leukemia, the clinical presentation of multiple myeloma bone disease, anemia, renal impairment, hypercalcemia, and neurologic symptoms associated with multiple myeloma. Therapy for transplantation-eligible and non–transplantation-eligible patients, maintenance treatment for multiple myeloma, Waldenström macroglobulinemia, and amyloidosis are also discussed. Tables outline the risk of monoclonal gammopathy of undetermined significance evolution, the myeloma staging system, recommended diagnostic testing and uniform response criteria for myeloma, and commonly used regimens in the treatment of myeloma. Figures include a magnetic resonance image showing multiple plasmacytomas, tibial lytic lesion from myeloma, calvarial lytic lesions, a positron emission tomographic scan in a myeloma patient, and hyperviscosity causing retinal hemorrhages. This review contains 5 highly rendered figures, 5 tables, and 149 references.

Biology of the Transition of Monoclonal Gammopathy of Undetermined Significance (MGUS) to Multiple Myeloma

1998 ◽  
Vol 5 (3) ◽  
pp. 209-217 ◽  
Author(s):  
John A. Lust ◽  
Kathleen A. Donovan
Keyword(s):  
Multiple Myeloma ◽  
Adhesion Molecules ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Therapeutic Strategies ◽  
Plasma Cell Disorder ◽  
Novel Therapeutic Strategies ◽  
Cell Disorder ◽  
Undetermined Significance

Background Approximately 25% of patients with monoclonal gammopathy of undetermined significance (MGUS) eventually develop multiple myeloma (MM) or a related plasma cell disorder that is universally fatal. In this report, we examine the changes that occur in the clonal plasma cell that are likely to be important in the progression of MGUS to active myeloma. Methods Studies that investigate the mechanisms involved in the multistep pathogenesis of monoclonal gammopathies are reviewed. Cytokines such as IL- 6 and IL-1β, adhesion molecules, viruses, and oncogenes including ras, bcl-2, Rb, and p53 are discussed. Results IL-1β is produced by plasma cells from virtually all MM patients but is undetectable in most MGUS patients. IL-1β has potent osteoclast activating factor activity, can increase the expression of adhesion molecules, and can induce paracrine IL-6 production. The increased production of adhesion molecules could explain why myeloma cells are found predominantly in the bone marrow. Subsequently, these “fixed” monoclonal plasma cells could now stimulate osteoclasts through the production of IL-1β and paracrine generation of IL-6 resulting in osteolytic disease. With continued progression of the myeloma, the monoclonal plasma cells may later acquire the ability to produce IL-6 in an autocrine fashion that will be manifested clinically by an elevated labeling index. Conclusions A better understanding of the progression of MGUS to myeloma may lead to novel therapeutic strategies to prevent the development of MM.

Aurora kinase A is a target of Wnt/β-catenin involved in multiple myeloma disease progression

Blood ◽  
2009 ◽  
Vol 114 (13) ◽  
pp. 2699-2708 ◽  
Author(s):  
Jui Dutta-Simmons ◽  
Yunyu Zhang ◽  
Gullu Gorgun ◽  
Moshe Gatt ◽  
Mala Mani ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Progression ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Aurora Kinase ◽  
The United States ◽  
Functional Link ◽  
Aurora Kinase A ◽  
Kinase A ◽  
Undetermined Significance

Abstract Multiple myeloma (MM) is a cancer of plasma cells with complex molecular characteristics that evolves from monoclonal gammopathy of undetermined significance, a highly prevalent premalignant condition. MM is the second most frequent hematologic cancer in the United States, and it remains incurable, thereby highlighting the need for new therapeutic approaches, particularly those targeting common molecular pathways involved in disease progression and maintenance, shared across different MM subtypes. Here we report that Wnt/β-catenin is one such pathway. We document the involvement of β-catenin in cell-cycle regulation, proliferation, and invasion contributing to enhanced proliferative and metastatic properties of MM. The pleiotropic effects of β-catenin in MM correlate with its transcriptional function, and we demonstrate regulation of a novel target gene, Aurora kinase A, implicating β-catenin in G2/M regulation. β-catenin and Aurora kinase A are present in most MM but not in normal plasma cells and are expressed in a pattern that parallels progression from monoclonal gammopathy of undetermined significance to MM. Our data provide evidence for a novel functional link between β-catenin and Aurora kinase A, underscoring a critical role of these pathways in MM disease progression.

scholarly journals Clinical, morphological, and cell kinetic differences among multiple myeloma, monoclonal gammopathy of undetermined significance, and smoldering multiple myeloma

Blood ◽  
1983 ◽  
Vol 62 (1) ◽  
pp. 166-171 ◽  
Author(s):  
PR Greipp ◽  
RA Kyle
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Labeling Index ◽  
Cell Labeling ◽  
Linear Discriminant ◽  
Smoldering Multiple Myeloma ◽  
Undetermined Significance

We reviewed the clinical and morphological findings in 43 cases of monoclonal gammopathy of undetermined significance (MGUS), 9 of smoldering multiple myeloma (SMM), and 23 of overt multiple myeloma (MM). In all cases, the patients' physicians had requested a bone marrow examination because of the possibility of MM. In all 75 cases, 3H-thymidine labeling indices were performed. The plasma cell labeling index correctly classified 62 of the 75 cases (83%). A linear discriminant function combining the labeling index and percentage of plasma cells improved the accuracy to 92% (69/75), or to 95% (71/75) if patients in whom MM developed within 6 mo were considered to have MM. The labeling index was most critical for the differential diagnosis of MM from SMM (p less than 0.001). Serum or urine M-protein level, percentage of plasma cells or lymphocytes in the bone marrow, and plasma cell grade, asynchrony, and nucleolar size failed to discriminate the group with SMM from the group with MM. In patients with MGUS or SMM, a plasma cell labeling index greater than 0.4% warned of impending MM. The plasma cell labeling index is a reliable diagnostic test when applied in cases of monoclonal gammopathy, especially when differentiation from MM is difficult using standard clinical criteria.

scholarly journals Clinical, morphological, and cell kinetic differences among multiple myeloma, monoclonal gammopathy of undetermined significance, and smoldering multiple myeloma

Blood ◽  
1983 ◽  
Vol 62 (1) ◽  
pp. 166-171 ◽  
Author(s):  
PR Greipp ◽  
RA Kyle
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Labeling Index ◽  
Cell Labeling ◽  
Linear Discriminant ◽  
Smoldering Multiple Myeloma ◽  
Undetermined Significance

Abstract We reviewed the clinical and morphological findings in 43 cases of monoclonal gammopathy of undetermined significance (MGUS), 9 of smoldering multiple myeloma (SMM), and 23 of overt multiple myeloma (MM). In all cases, the patients' physicians had requested a bone marrow examination because of the possibility of MM. In all 75 cases, 3H-thymidine labeling indices were performed. The plasma cell labeling index correctly classified 62 of the 75 cases (83%). A linear discriminant function combining the labeling index and percentage of plasma cells improved the accuracy to 92% (69/75), or to 95% (71/75) if patients in whom MM developed within 6 mo were considered to have MM. The labeling index was most critical for the differential diagnosis of MM from SMM (p less than 0.001). Serum or urine M-protein level, percentage of plasma cells or lymphocytes in the bone marrow, and plasma cell grade, asynchrony, and nucleolar size failed to discriminate the group with SMM from the group with MM. In patients with MGUS or SMM, a plasma cell labeling index greater than 0.4% warned of impending MM. The plasma cell labeling index is a reliable diagnostic test when applied in cases of monoclonal gammopathy, especially when differentiation from MM is difficult using standard clinical criteria.

Interleukin‐6 is expressed by plasma cells from patients with multiple myeloma and monoclonal gammopathy of undetermined significance

1998 ◽  
Vol 101 (2) ◽  
pp. 287-295 ◽  
Author(s):  
Hamdi I. A. Sati ◽  
Jane F. Apperley ◽  
Mike Greaves ◽  
John Lawry ◽  
Roger Gooding ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Interleukin 6 ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Undetermined Significance

scholarly journals Single Arm, Prospective, Open-Label Phase II Trial to Evaluate the Efficacy of Isatuximab in Patients with Monoclonal Gammopathy of Renal Significance

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3161-3161 ◽  
Author(s):  
Vikram Premkumar ◽  
Suzanne Lentzsch ◽  
Divaya Bhutani
Keyword(s):  
Multiple Myeloma ◽  
B Cell ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Cell Clone ◽  
Advisory Committees ◽  
Renal Response ◽  
Hematologic Response ◽  
Stable Renal Function

Background: Monoclonal gammopathy of renal significance (MGRS) is a monoclonal B cell disorder, not meeting the definition of lymphoma or myeloma, that produces monoclonal proteins which deposit in the kidneys. Permanent renal damage can occur either as a consequence of direct deposition of toxic proteins or by an induced inflammatory response. Due to the low burden of the plasma cell clone, patients do not otherwise qualify for potentially toxic anti-plasma cell treatments and treatment is generally based on consensus opinion. To date there are no clinical trials exploring treatment options. Isatuximab is a chimeric mouse/human IgG1k monoclonal antibody which targets CD38 on both malignant and normal plasma cells and exhibits it antitumor effects primarily by antibody-dependent cellular toxicity. Isatuximab has recently been shown to be an active drug in the treatment of multiple myeloma, with improvements seen in hematologic and renal markers, and has been shown to have manageable toxicity. Given the efficacy of isatuximab in multiple myeloma, we propose a trial evaluating isatuximab monotherapy to treat the small plasma cell clone in MGRS with the hopes of maximizing response and minimizing toxicity. Study Design and Methods: The primary objective of this study is to evaluate efficacy of isatuximab monotherapy in patients with MGRS in order to establish a standard of care treatment for patients with this disease. Adult patients with proteinuria of at least 1 gram in 24 hours and a histopathological diagnosis of MGRS on renal biopsy in the last 24 months will be eligible for the trial. Patients will be excluded if their estimated GFR is below 30 mL/min, they have multiple myeloma, high risk smoldering myeloma, other B cell neoplasm meeting criteria for treatment, concurrent diabetic nephropathy, or require dialysis. Patients will be screened for B cell disorders with bone marrow biopsy and aspirate, serum protein electrophoresis (SPEP) with immunofixation (IFE), 24-hour urine protein electrophoresis (UPEP), free light chain (FLC) testing and screening PET/CT at time of enrollment. Enrolled patients will be administered isatuximab 20 mg/kg IV weekly for 4 weeks and then will receive the same dose every 2 weeks thereafter for a total of 6 months. Patients may be continued on treatment following completion of the 6 months at the discretion of the provider. To reduce the risk of infusion related reactions, patients will receive premedications with corticosteroids, diphenhydramine, H2 blockade and acetaminophen at least 60 minutes prior to infusion. Patients will have repeat SPEP + IFE, 24-hour UPEP + IFE and FLC testing every 4 weeks. There will be an optional repeat kidney biopsy 9-12 months following treatment initiation to assess pathologic response in the kidneys. Statistical Methods: The study will be comprised of 20 patients being treated with isatuximab over a span of 24-30 months. Ten patients will be initiated on the therapy for a period of 6 months. Interim analysis will be done after these patients have completed all the treatment cycles. If 4 out of 10 patients show response in form of improved/stable renal function, the study will proceed to include next 10 patients. If >50% of the first group of 10 patients show doubling of creatinine while on therapy, that would be considered as an indication to discontinue the therapy and the study due to drug toxicity. Endpoints: The primary endpoint will be efficacy as measured by renal response and hematologic response. Renal response will be measured by assessing the amount of proteinuria in a 24 hour urine sample. A sustained reduction in proteinuria by 30% from the patient's baseline amount of proteinuria with stable renal function (serum eGFR within 20% of baseline) will be considered a positive renal response. Hematologic response will be quantified per the 2016 International Myeloma Working Group (IMWG) uniform response criteria for multiple myeloma. An important secondary endpoint will be safety and will be analyzed from all patients who receive any study drug. Adverse events will be characterized and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Other endpoints include time to dialysis and rate of minimal residual disease (MRD) negativity. Disclosures Lentzsch: Caelum Biosciences: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy; Janssen: Consultancy; Takeda: Consultancy; BMS: Consultancy; Proclara: Consultancy; Abbvie: Consultancy; Clinical Care Options: Speakers Bureau; Sanofi: Consultancy, Research Funding; Multiple Myeloma Research Foundation: Honoraria; International Myeloma Foundation: Honoraria; Karyopharm: Research Funding; Columbia University: Patents & Royalties: 11-1F4mAb as anti-amyloid strategy. Bhutani:Sanofi: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Our trial will be evaluating the efficacy of targeting CD38 on plasma cells with isatuximab in patients with monoclonal gammopathy of renal significance (MGRS). We will evaluate the effects of this drug on 24 hour proteinuria and hematologic response.

scholarly journals Ig VH gene mutational patterns indicate different tumor cell status in human myeloma and monoclonal gammopathy of undetermined significance

Blood ◽  
1996 ◽  
Vol 87 (2) ◽  
pp. 746-755 ◽  
Author(s):  
SS Sahota ◽  
R Leo ◽  
TJ Hamblin ◽  
FK Stevenson
Keyword(s):  
Multiple Myeloma ◽  
Tumor Cell ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Somatic Hypermutation ◽  
Wide Spectrum ◽  
Malignant Potential ◽  
Gene Sequences ◽  
Vh Gene ◽  
Undetermined Significance

Plasma cell tumors display a wide spectrum of clinical progression, ranging from aggressive multiple myeloma to a benign form known as monoclonal gammopathy of undetermined significance (MGUS), which requires no treatment. Because both diseases involve mature Ig- secreting plasma cells, the reason for this variation in malignant behavior is unclear. However, assessment of malignant potential is desirable for choice of treatment protocols. Ig variable (VH) gene sequences analysis has previously shown the tumor cell of multiple myeloma to be postfollicular, with mutated homogeneous clonal sequences indicating no continuing exposure to the somatic hypermutation mechanism, and this was confirmed in 7 of 7 patients. Comparison of the VH gene sequences in the monoclonal cells in MGUS yielded a different result, with 3 of 7 patients demonstrating mutated heterogeneous sequences consistent with the tumor cells remaining under the influence of the mutator. In 1 of 3 of these patients, an IgM-positive precursor cell was identified that expressed heterogeneous VH sequences similar to those of the isotype-switched plasma cell. These results indicate that the clonal cells in MGUS differ from those in myeloma and suggest that the difference may reflect malignant potential.

Sign in / Sign up

Export Citation Format

Share Document