Predictive Significance of Serum Beta 2-Microglobulin Levels and M-Protein Velocity for Symptomatic Progression of Smoldering Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3379-3379 ◽  
Author(s):  
Tsuyoshi Muta ◽  
Shinsuke Iida ◽  
Kosei Matsue ◽  
Kazutaka Sunami ◽  
Jun Isoda ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cumulative Incidence ◽  
Plasma Cells ◽  
M Protein ◽  
Bone Lesions ◽  
Landmark Point ◽  
Protein Levels ◽  
Lytic Bone Lesions ◽  
Bone Marrow Plasma ◽  
Beta 2 Microglobulin

Abstract Background: Smoldering multiple myeloma (SMM) has been defined as precursor state to symptomatic multiple myeloma (MM). Mayo Clinic demonstrated that the presence of bone marrow plasma cells (BMPC) ≥ 10% and M protein levels ≥ 3 g/dL significantly associated with early progression to symptomatic MM and the serum free-light chain (FLC) ratio of < 0.125 or 8 < was an important additional predictors of progression. PETHEMA showed that the proportion of aberrant plasma cells (aPCs) within the BMPC > 95% as assessed by flow cytometry was another important variable for progression. However, NIH demonstrated the discordance of these two risk models. The aim of this project is to develop the method to predict the symptomatic progression more definitely by simple parameters, usually available at medical practice. Methods: We employed the nation-wide retrospective study. The clinical data of SMM patients were collected from 61 medical centers in Japan and risk predictors of progression to symptomatic MM were analyzed. The diagnosis of SMM is made by the presence of the ratio of bone marrow plasma cells (BMPCs) ≥ 10% or serum M-protein levels ≥ 3 g/dL, and the absence of any myeloma derived end-organ damage. Eligible patients were aged 18 to 90 years, previously untreated, and diagnosed between 2000 and 2012. This study was approved by the institutional review board at all participating institutions. Results: Total 301 patients fulfilled the inclusion criteria. The median age was 67 years (rang 27 to 90). IgG is the major (80%) compared to IgA (15%) or Bence Jones protein (3%). Total 145 patients developed to symptomatic MM. The symptoms consisted of anemia in 66%, lytic bone lesions in 43%, and renal impairment in 10%. Both anemia and lytic bone lesions were seen in 16%. The median time to progression was 4.3 years. The cumulative incidence of progression was 30.7% at 2 years, 50.0% at 4 years, 59.8% at 6 years, and 68.6% at 8 years. Based on multivariate analysis, we firstly identify the serum beta 2-microglobulin (B2MG) levels ≥ 2.5 mg/L as a predictor for the early progression (HR 1.59; 95% CI, 1.11 to 2.29, p = 0.01), as well as the known factors: presence of both BMPC ≥ 10% and M protein levels ≥ 3 g/dL (HR 1.89; 95% CI, 1.31 to 2.73, p = 0.0007), IgA or Bence Jones type (HR:1.61; 95%CI, 1.04 to 2.49, p = 0.03), and immunoparesis (HR:1.88; 95%CI, 1.14 to 3.08, p = 0.01). FLC ratio was examined in 52 patients. A significant association with high risk of progression was observed in patients with FLC ratio of < 0.0625 or 16 < (P = 0.04), but not in those with the ratio of < 0.125 or 8 < (P = 0.09). Cytogenetic abnormality was examined with FISH in 82 patients. The cumulative incidence of progression in patients with either t(4;14), t(14;16), or del(17p) was not significantly different from those without such chromosomal aberration (P = 0.4). Notably, we firstly focused on the rate of rise of the M-protein levels over time which is referred to as the "M-protein velocity". We employed the linear regression analysis to estimate the gradient to assess the M-protein velocity of each patient. The receiver operating characteristics curve analysis showed that the M-protein velocity of 1.035 mg/dL/day was a risk-stratification cut-off point with a high specificity of 0.96 and with a moderate sensitivity of 0.60. Based on the landmark analysis, the serum B2MG levels ≥ 2.5 mg/L at diagnosis (HR 2.76; 95% CI, 1.69 to 4.51, P = 5 x 10–5) and the M-protein velocity > 1 mg/dL/day before the 18-month landmark point (HR 2.27; 95% CI, 1.30 to 3.95, P = 4 x 10–3) had independently correlated with subsequent progression to symptomatic MM. The cumulative incidence of progression of the patients with both the serum B2MG levels ≥ 2.5 mg/L at diagnosis and the M-protein velocity > 1 mg/dL/day showed 67.5% at 2 years, 75.6% at 3 years and 100% at 6.3 years after the landmark point. Conclusions: We identify the novel risk factors consisted of serum B2MG levels ≥ 2.5 mg/L and the M-protein velocity > 1 mg/dL/day for subsequent symptomatic progression. Theoretically, it is possible to emphasis that the serum B2MG levels represent the initial tumor burden of SMM and the M-protein velocity reflects the the growth rate of tumor cells. These results also suggest that the quantification of time-dependent change of measured values should be taken into consideration for the precise prediction of symptomatic progression. This study is supported by the National Cancer Center Research and Development Fund in Japan. Disclosures No relevant conflicts of interest to declare.

scholarly journals An Unprecedented Case of p190 BCR-ABL Chronic Myeloid Leukemia Diagnosed during Treatment for Multiple Myeloma: A Case Report and Review of the Literature

2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Kosuke Miki ◽  
Naoshi Obara ◽  
Kenichi Makishima ◽  
Tatsuhiro Sakamoto ◽  
Manabu Kusakabe ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Plasma Cells ◽  
Bone Marrow Examination ◽  
Bone Lesions ◽  
Dexamethasone Treatment ◽  
Lytic Bone Lesions

We report the case of a 76-year-old man who was diagnosed as having chronic myeloid leukemia (CML) with p190 BCR-ABL while receiving treatment for symptomatic multiple myeloma (MM). The diagnosis of MM was based on the presence of serum M-protein, abnormal plasma cells in the bone marrow, and lytic bone lesions. The patient achieved a partial response to lenalidomide and dexamethasone treatment. However, 2 years after the diagnosis of MM, the patient developed leukocytosis with granulocytosis, anemia, and thrombocytopenia. Bone marrow examination revealed Philadelphia chromosomes and chimeric p190 BCR-ABL mRNA. Fluorescence in situ hybridization also revealed BCR-ABL-positive neutrophils in the peripheral blood, which suggested the emergence of CML with p190 BCR-ABL. The codevelopment of MM and CML is very rare, and this is the first report describing p190 BCR-ABL-type CML coexisting with MM. Moreover, we have reviewed the literature regarding the coexistence of these diseases.

Extensive Bone Marrow Infiltration and Abnormal Free Light Chain Ratio Identifies Patients with Smoldering Myeloma At High Risk for Progression to Symptomatic Disease,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3926-3926
Author(s):  
Efstathios Kastritis ◽  
Lia A Moulopoulos ◽  
Maria Gkotzamanidou ◽  
Dimitra Gika ◽  
Maria Roussou ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Light Chain ◽  
Plasma Cells ◽  
Bone Lesions ◽  
Symptomatic Disease ◽  
Lytic Bone Lesions ◽  
Risk Of Progression ◽  
Bone Marrow Plasma ◽  
Substantial Risk

Abstract Abstract 3926 Asymptomatic/smoldering multiple myeloma (SMM) is a proliferative plasma cell disorder characterized by a substantial risk of progression to symptomatic myeloma. According to current recommendations, patients with SMM should be followed without treatment until they develop symptomatic disease. However, the risk of progression to symptomatic myeloma varies between different series and for individual patients; thus, significant effort is needed in order to identify factors that could discriminate those who are at high risk for progression. Such patients should be followed closer and should be considered candidates for clinical trials. In order to evaluate previously recognized risk factors and study patterns of progression we analyzed our series of patients with SMM, who have been diagnosed and followed in the Department of Clinical Therapeutics in Athens, Greece. SMM was defined as serum monoclonal (M) protein (IgG or IgA) level of ≥3 g/dL and/or bone marrow plasma cells ≥10%, absence of end-organ damage, such as lytic bone lesions, anemia, hypercalcemia, or renal failure, that can attributed to a plasma cell proliferative disorder (IMWG criteria, Br J Haematol 2003;121:749–57). Progression to symptomatic myeloma was defined as per the IMWG proposed criteria. We analyzed 95 patients with SMM, 53% of whom were females, 70% had IgG heavy chain, 22% had IgA, 5% had a biclonal SMM and 3% had light chain only SMM, while 65% had a kappa light chain and 35% a lambda light chain. Median infiltration by clonal plasma cells in BM trephine biopsy was 20% (range 10–90%), 10% of patients had ≥60% clonal plasma cells in BM biopsy. Fifty patients had MRI of the spine at the time of diagnosis of SMM and 19.5% had an abnormal pattern of BM infiltration (diffuse, focal or variegated pattern). In patients with available bone marrow immunohistochemistry data, 61% had clonal plasma positive for CD56, 17% for CD20 and 19% for cyclin D1. The median follow up of the cohort was 27 months (range 1–253 months) and 23 (24%) patients have progressed to symptomatic myeloma. The one-year, 2-year and 3-year cumulative probability of progression was 7%, 12% and 20% respectively. Nine patients (9.5%) progressed within the first two years from the diagnosis of SMM. All these patients had an M-protein of ≥1 g/dl (10 g/L), 67% had bone marrow plasma cells >60% and 80% had an abnormal MRI pattern of BM infiltration. The 3-year probability of progression to symptomatic myeloma was 4%, 18% and 87% for patients with <20%, 20–59% and ≥60% clonal plasma cells in bone marrow biopsy (P<0.001). The 2-year probability of progression to symptomatic myeloma was 0%, 13% and 60% for patients with <20%, 20–59% and ≥60% clonal plasma cells in BM biopsy (P<0.001). Patients with significantly abnormal free light chain ratio (either kappa/lambda ≥8 or kappa/lambda ≤0.125, according to Dispenzieri et al, Blood 2008;111:785–9) had a 3-year probability of progression to symptomatic MM of 41% vs. 15% (p=0.07). There was no significant difference in the risk of progression to symptomatic MM for patients with IgA vs. IgG myeloma. In multivariate analysis, abnormal FLC ratio less than 0.125 or more than 8 (HR: 6.4, 95% CI 1.3–34.5 p=0.032) and BM clonal plasma cells infiltration ≥60% (HR: 23, 95% CI 5–125, p<0.001) were independent risk factors for progression to symptomatic myeloma. Progression to symptomatic MM was manifested by the development of anemia in 52% of patients who progressed to symptomatic MM, development of lytic bone lesions or pathologic fracture in 48%, an increase of serum creatinine to ≥2 mg/dl in 13%, development of a soft tissue plasmacytoma in 4% and development of hypercalcemia in 4%. In conclusion, in our series of patients the 3-year probability of progression to symptomatic myeloma is about 20%, but there is a subgroup of patients with extensive bone marrow infiltration (≥60%) and highly abnormal FLC ratio, who have a substantial risk of progression to symptomatic disease within the first two years from the diagnosis of SMM. These high risk patients may also have other features such as abnormal MRI of the spine. Patients at high risk for progression should be considered for clinical trials evaluating the role of treatment before the development of symptomatic disease, which in most cases is manifested with anemia and/or lytic bone disease or pathologic fractures. Disclosures: No relevant conflicts of interest to declare.

The Natural History of Smoldering (Asymptomatic) Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3396-3396 ◽  
Author(s):  
Robert Kyle ◽  
Ellen Remstein ◽  
Terry Therneau ◽  
Angela Dispenzieri ◽  
Paul Kurtin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Light Chain ◽  
Plasma Cells ◽  
M Protein ◽  
Cell Content ◽  
Bone Marrow Plasma ◽  
M Spike

Abstract Smoldering multiple myeloma (SMM) is characterized by a serum M protein ≥ 3g/dL and/or 10% or more of plasma cells in the bone marrow. However, the definition is not standardized, and it is not known whether both serum M protein levels and bone marrow plasma cell counts are necessary for diagnosis or if one parameter is sufficient. We reviewed the medical records and bone marrows of all patients from Mayo Clinic seen within 30 days of recognition of an IgG or IgA M protein ≥ 3g/dL or a bone marrow containing ≥ 10% plasma cells from 1970 to 1995. This allows for a minimum potential follow-up of 10 years. Patients with end-organ damage at baseline from plasma cell proliferation, including active multiple myeloma (MM) and primary amyloidosis (AL) and those who had received chemotherapy were excluded. A differential of the bone marrow aspirate coupled with the bone marrow biopsy morphology and immunohistochemistry using antibodies directed against CD138, MUM-1 and Cyclin D1 were evaluated in every case in order to estimate the plasma cell content. In all, 301 patients fulfilled either of the criteria for SMM. Their median age was 64 years and only 3% were less than 40 years of age; 60% were male. The median hemoglobin value was 12.9 g/dL; 7% were less than 10 g/dL, but the anemia was unrelated to plasma cell proliferation. IgG accounted for 75%, IgA 22%, and biclonal proteins were found in 3%. The serum light-chain was κ in 67% and λ in 33%. The median serum M spike was 2.9 g/dL; 11% were at least 4.0 g/dL. Uninvolved serum immunoglobulins were reduced in 81%; only 1 immunoglobulin was reduced in 31% and both were decreased in 50%. The urine contained a monoclonal κ protein in 36% and λ in 18% and 46% were negative. The median size of the urine M spike was 0.04 g/24h; only 5 (3%) were &gt; 1 g/24h. The median bone marrow plasma cell content was 15 – 19%; 10% had less than 10% plasma cells, while 10% had at least 50% plasma cells in the bone marrow. Cyclin D-1 was expressed in 17%. Patients were categorized into 3 groups: Group 1, serum M protein ≥ 3g/dL and bone marrow containing ≥ 10% plasma cells (n= 113, 38%); Group 2, bone marrow plasma cells ≥ 10% but serum M protein &lt; 3g/dL (n= 158, 52%); Group 3, serum M protein ≥ 3g/dL but bone marrow plasma cells &lt; 10% (n= 30, 10%). During 2,204 cumulative years of follow-up 85% died (median follow-up of those still living 10.8 years), 155 (51%) developed MM, while 7 (2%) developed AL. The overall rate of progression at 10 years was 62%; median time to progression was 5.5 yrs. The median time to progression was 2.4, 9.2, and 19 years in groups 1, 2, and 3 respectively; correspondingly at 10 years, progression occurred in 76%, 59%, and 32% respectively. Significant risk factors for progression with univariate analysis were serum M spike ≥ 4g/dL (p &lt; 0.001), presence of IgA (p = 0.003), presence of urine light chain (p = 0.006), presence of λ urinary light chain (p = 0.002), bone marrow plasma cells ≥ 20% (p &lt; 0.001) and reduction of uninvolved immunoglobulins (p &lt; 0.001). The hemoglobin value, gender, serum albumin, and expression of cyclin D-1 were not of prognostic importance. On multivariate analysis, the percentage of bone marrow plasma cells was the only significant factor predicting progression to MM or AL.

Immunoglobulin Free Light Chain Ratio Is an Independent Risk Factor for Progression of Smoldering Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1487-1487 ◽  
Author(s):  
Angela Dispenzieri ◽  
Robert A. Kyle ◽  
Jerry A. Katzmann ◽  
Dirk Larson ◽  
Joanne Benson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Light Chain ◽  
Plasma Cells ◽  
Free Light Chain ◽  
M Protein ◽  
Baseline Serum ◽  
Smoldering Multiple Myeloma ◽  
Risk Of Progression ◽  
Bone Marrow Plasma

Abstract Background: Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell proliferative disorder with a high risk of progression to symptomatic multiple myeloma. Identification of risk factors that predict progression of SMM to symptomatic MM could identify higher risk patients who might benefit from chemoprevention or more intensive surveillance. We hypothesized that increased monoclonal free kappa or lambda immunoglobulin light chains in smoldering myeloma (SMM), as detected by the serum free light chain (FLC) assay, indicates an increased the risk of progression to active myeloma. Methods: Of 276 pathologically confirmed SMM patients seen at the Mayo Clinic from 1970 to 1995, baseline serum samples obtained within 30 days of diagnosis were available in 273. Results: At a median follow-up of surviving patients of 12.4 years, transformation to active disease has occurred in 161 (59%) patients. An abnormal FLC ratio was present at baseline in 90% of patients. The best break-point for predicting risk of progression was a FLC ratio less than or equal to 0.125 or greater than or equal to 8 (hazard ratio, 2.3; 95% CI, 1.6–3.2) [Figure 1]. The extent of abnormality of FLC ratio was independent of SMM risk categories defined by number of plasma cells in the bone marrow and size of serum M-proteins (bone marrow plasma cells ≥ 10% and serum M protein ≥ 3 g/dL; bone marrow plasma cells ≥ 10% but serum M protein &lt; 3 g/dL; and serum M protein ≥ 3 g/dL but bone marrow plasma cells &lt; 10%). Incorporating the FLC ratio into the risk model, the division of patients into high-, intermediate-, and low-risk groups is 28, 42, and 30% with 5 year progression rates of 76, 51, and 25%, respectively [Figure 2]. Conclusions: The serum immunoglobulin FLC ratio is an important additional determinant of clinical outcome in patients with SMM. Figure Figure Figure Figure

scholarly journals Smoldering Multiple Myeloma

2015 ◽  
Vol 2015 ◽  
pp. 1-7
Author(s):  
Minjie Gao ◽  
Guang Yang ◽  
Yuanyuan Kong ◽  
Xiaosong Wu ◽  
Jumei Shi
Keyword(s):  
Multiple Myeloma ◽  
Early Treatment ◽  
Plasma Cells ◽  
Intermediate Stage ◽  
Organ Damage ◽  
M Protein ◽  
Smoldering Multiple Myeloma ◽  
Risk Of Progression ◽  
Bone Marrow Plasma ◽  
Peripheral Blood Plasma

Smoldering multiple myeloma (SMM) is an asymptomatic precursor stage of multiple myeloma (MM) characterized by clonal bone marrow plasma cells (BMPC) ≥ 10% and/or M protein level ≥ 30 g/L in the absence of end organ damage. It represents an intermediate stage between monoclonal gammopathy of undetermined significance (MGUS) and symptomatic MM. The risk of progression to symptomatic MM is not uniform, and several parameters have been reported to predict the risk of progression. These include the level of M protein and the percentage of BMPC, the proportion of immunophenotypically aberrant plasma cells, and the presence of immunoparesis, free light-chain (FLC) ratio, peripheral blood plasma cells (PBPC), pattern of serum M protein evolution, abnormal magnetic resonance imaging (MRI), cytogenetic abnormalities, IgA isotype, and Bence Jones proteinuria. So far treatment is still not recommended for SMM, because several trials suggested that patients with SMM do not benefit from early treatment. However, the Mateos et al. trial showed a survival benefit after early treatment with lenalidomide plus dexamethasone in patients with high-risk SMM. This trial has prompted a reevaluation of early treatment in an asymptomatic patient population.

scholarly journals A Phase II Study of Daratumumab in Patients with High-Risk MGUS and Low-Risk Smoldering Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1649-1649
Author(s):  
Omar Nadeem ◽  
Robert A. Redd ◽  
Michael Z. Koontz ◽  
Jeffrey V. Matous ◽  
Andrew J. Yee ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
High Risk ◽  
Board Of Directors ◽  
Research Funding ◽  
Plasma Cells ◽  
Low Risk ◽  
M Protein ◽  
Advisory Committees ◽  
Bone Marrow Plasma

Abstract Introduction : Daratumumab (Dara) is an anti-CD38 monoclonal antibody that is approved for use in patients with newly diagnosed and relapsed multiple myeloma (MM). We hypothesized that early therapeutic intervention with Dara in patients with high-risk MGUS (HR-MGUS) or low-risk SMM (LR-SMM) would lead to eradication of the tumor clone by achieving deep responses, resulting in prevention of progression to MM. We present results of our phase II, single arm study of Dara in HR-MGUS and LR-SMM. Methods : Patients enrolled on this study met eligibility for either HR-MGUS or LR-SMM. HR-MGUS is defined as &lt;10% bone marrow plasma cells and &lt;3g/dL M protein and at least 2 of the following 3 high-risk criteria: Abnormal serum free light chain ratio (SFLC) of &lt;0.26 or &gt;1.65, M protein ≥ 1.5g/dL or non-IgG M protein. LR-SMM is defined by one of the following 3 criteria: M protein ≥3g/dL, ≥10% bone marrow plasma cells, SFLC ratio &lt;0.125 or &gt;8. Dara (16mg/kg) was administered intravenously on a weekly schedule for cycles 1-2, every other week cycles 3-6, and monthly during cycles 7-20. The primary objective of this study was to determine the proportion of patients who achieve very good partial response (VGPR) or greater after 20 cycles of Dara. Secondary objectives included duration of response, safety, and rates of minimal residual disease (MRD)-negativity in VGPR or greater patients. Correlative studies included assessing changes in immune microenvironment, evaluating clonal heterogeneity using deep sequencing, and determining association of genomic aberrations correlating with either response to therapy or progression of disease. Results : At the time of data cutoff, a total of 42 patients were enrolled on this study from 2018 to 2020 with participation of 5 sites. The median age for all patients at enrolment was 60 years (range 38 to 76), with 22 males (52.4%) and 20 females (47.6%). Majority of patients enrolled were classified as LR-SMM (n = 37, 88.1%) and the remaining 5 patients had HR-MGUS (11.9%). 41 patients have started treatment and are included in toxicity assessment, and 40 patients have at least completed 16 cycles (range 6-20). Grade 3 toxicities were rare and only experienced in 5/41 patients including diarrhea (n =1/41; 2%), flu like symptoms (n = 1/41; 2%), headache (n=1/41; 2%), and hypertension (n=2/41; 5%). Most common toxicities of any grade included fatigue (n = 24/41, 51%), cough (n = 19/41, 46%), nasal congestion (n = 18/41, 44%), headache (n = 14/41, 34%), hypertension (n = 11/41, 27%), nausea (n = 13/41, 32%), and leukopenia (n = 13/41, 32%). No patients have discontinued therapy due to toxicity. Minimal response or better was observed in 82.9% of patients (34/41) and PR or better was observed in 51.2% of patients (21/41). This included overall CR (n = 4, 9.8%), VGPR (n = 1, 2.4%), PR (n = 16, 39.0%), MR (n = 13, 31.7%), and SD (n = 7, 17.1%). In the 40 patients who completed at least 16 cycles, response rates were as follows: MR or better 85% (34/40), PR or better 52.5% (21/40) and VGPR or better 12.5% (5/40). Median time to VGPR was 7 months. Median overall survival and progression-free survival have not been reached and no patients have progressed to overt multiple myeloma while on study. Conclusion : Dara is very well tolerated among patients with HR-MGUS and LR-SMM with minimal toxicities. Responses are seen in majority of patients. Early therapeutic intervention in this precursor patient population appears promising but longer follow up is required to define the role of single agent Dara in preventing progression to MM, therefore avoiding more toxic interventions in this low-risk patient population. Disclosures Nadeem: Karyopharm: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Yee: GSK: Consultancy; Oncopeptides: Consultancy; Janssen: Consultancy; Amgen: Consultancy; Sanofi: Consultancy; Bristol Myers Squibb: Consultancy; Adaptive: Consultancy; Takeda: Consultancy; Karyopharm: Consultancy. Zonder: Caelum Biosciences: Consultancy; Amgen: Consultancy; BMS: Consultancy, Research Funding; Intellia: Consultancy; Alnylam: Consultancy; Janssen: Consultancy; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy. Rosenblatt: Attivare Therapeutics: Consultancy; Imaging Endpoints: Consultancy; Parexel: Consultancy; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; Wolters Kluwer Health: Consultancy, Patents & Royalties. Mo: AbbVIE: Consultancy; BMS: Membership on an entity's Board of Directors or advisory committees; Eli Lilly: Consultancy; Epizyme: Consultancy; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Sperling: Adaptive: Consultancy. Richardson: Karyopharm: Consultancy, Research Funding; AstraZeneca: Consultancy; AbbVie: Consultancy; Takeda: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding; Janssen: Consultancy; GlaxoSmithKline: Consultancy; Protocol Intelligence: Consultancy; Secura Bio: Consultancy; Regeneron: Consultancy; Sanofi: Consultancy; Oncopeptides: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding. Ghobrial: AbbVie, Adaptive, Aptitude Health, BMS, Cellectar, Curio Science, Genetch, Janssen, Janssen Central American and Caribbean, Karyopharm, Medscape, Oncopeptides, Sanofi, Takeda, The Binding Site, GNS, GSK: Consultancy.

scholarly journals Plasmacytoma as a Mimicker of Colonic Carcinoma in an Elderly Man

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Sara Mathew George ◽  
Eman Ali Aljufairi ◽  
Nisha Chandran ◽  
Sayed Ali Isa Almahari
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Gastrointestinal Tract ◽  
Gastrointestinal Bleeding ◽  
Plasma Cells ◽  
Bone Lesions ◽  
Lytic Bone Lesions ◽  
Plasma Cell Neoplasms ◽  
Bleeding Per Rectum ◽  
Tract Involvement

Multiple myeloma is a neoplastic proliferation of monoclonal plasma cells. Although it is usually restricted to the bone marrow, extraskeletal spread in the form of localised extramedullary collections of malignant plasma cells (plasmacytomas) can occur. However, gastrointestinal tract involvement in multiple myeloma is rare and overt gastrointestinal bleeding from plasmacytoma is uncommon. We report a case of colonic plasmacytoma which presented with bleeding per rectum and was initially misdiagnosed as colonic neuroendocrine carcinoma. Later the patient presented with recurrence of the colonic mass along with multiple lytic bone lesions. The diagnosis of colonic plasmacytoma with progression into multiple myeloma was given. We also discuss here the diagnostic difficulty of plasma cell neoplasms in small biopsies of the colon.

scholarly journals Coexistent Multiple Myeloma or Increased Bone Marrow Plasma Cells Define Equally High-Risk Populations in Patients With Immunoglobulin Light Chain Amyloidosis

2013 ◽  
Vol 31 (34) ◽  
pp. 4319-4324 ◽  
Author(s):  
Taxiarchis V. Kourelis ◽  
Shaji K. Kumar ◽  
Morie A. Gertz ◽  
Martha Q. Lacy ◽  
Francis K. Buadi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Light Chain ◽  
Plasma Cells ◽  
Survival Rates ◽  
Bone Lesions ◽  
Al Amyloidosis ◽  
Characteristic Analysis ◽  
Bone Marrow Plasma

Purpose There is consensus that patients with light chain (AL) amyloidosis with hypercalcemia, renal failure, anemia, and lytic bone lesions attributable to clonal expansion of plasma cells (CRAB criteria) also have multiple myeloma (MM). The aim of this study was to examine the spectrum of immunoglobulin AL amyloidosis with and without MM, with a goal of defining the optimal bone marrow plasma cell (BMPC) number to qualify as AL amyloidosis with MM. Patients and Methods We identified 1,255 patients with AL amyloidosis seen within 90 days of diagnosis between January 1, 2000, and December 31, 2010. We defined a population of patients with coexisting MM on the basis of the existence of CRAB criteria (AL-CRAB). Receiver operating characteristic analysis determined the optimal BMPC cut point to predict for 1-year mortality in patients with AL amyloidosis without CRAB to produce two additional groups: AL only (≤ 10% BMPCs) and AL plasma cell MM (AL-PCMM; > 10% BMPCs). Results Among the 1,255 patients, 100 (8%) had AL-CRAB, 476 (38%) had AL-PCMM, and 679 (54%) had AL only. Their respective median overall survival rates were 10.6, 16.2, and 46 months (P < .001). Because the outcomes of AL-CRAB and AL-PCMM were similar, they were pooled for univariate and multivariate analyses. On multivariate analysis, pooled AL-CRAB and AL-PCMM retained negative prognostic value independent of age, Mayo Clinic AL amyloidosis stage, prior autologous stem-cell transplantation, and difference between the involved and uninvolved free light chain. Conclusion Patients with AL amyloidosis who have more than 10% BMPCs have a poor prognosis, similar to that of patients with AL-CRAB, and should therefore be considered together as AL amyloidosis with MM.

Bone disease as the first manifestation of systemic AL-amyloidosis

2020 ◽  
Vol 92 (7) ◽  
pp. 85-89
Author(s):  
L. P. Mendeleeva ◽  
I. G. Rekhtina ◽  
A. M. Kovrigina ◽  
I. E. Kostina ◽  
V. A. Khyshova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bone Disease ◽  
Plasma Cells ◽  
Interventricular Septum ◽  
Bone Destruction ◽  
Amyloid Deposition ◽  
Bone Lesions ◽  
Al Amyloidosis ◽  
Linear Type

Our case demonstrates severe bone disease in primary AL-amyloidosis without concomitant multiple myeloma. A 30-year-old man had spontaneous vertebral fracture Th8. A computed tomography scan suggested multiple foci of lesions in all the bones. In bone marrow and resected rib werent detected any tumor cells. After 15 years from the beginning of the disease, nephrotic syndrome developed. Based on the kidney biopsy, AL-amyloidosis was confirmed. Amyloid was also detected in the bowel and bone marrow. On the indirect signs (thickening of the interventricular septum 16 mm and increased NT-proBNP 2200 pg/ml), a cardial involvement was confirmed. In the bone marrow (from three sites) was found 2.85% clonal plasma cells with immunophenotype СD138+, СD38dim, СD19-, СD117+, СD81-, СD27-, СD56-. FISH method revealed polysomy 5,9,15 in 3% of the nuclei. Serum free light chain Kappa 575 mg/l (/44.9) was detected. Multiple foci of destruction with increased metabolic activity (SUVmax 3.6) were visualized on PET-CT, and an surgical intervention biopsy was performed from two foci. The number of plasma cells from the destruction foci was 2.5%, and massive amyloid deposition was detected. On CT scan foci of lesions differed from bone lesions at multiple myeloma. Bone fragments of point and linear type (button sequestration) were visualized in most of the destruction foci. The content of the lesion was low density. There was no extraossal spread from large zones of destruction. There was also spontaneous scarring of the some lesions (without therapy). Thus, the diagnosis of multiple myeloma was excluded on the basis based on x-ray signs, of the duration of osteodestructive syndrome (15 years), the absence of plasma infiltration in the bone marrow, including from foci of bone destruction by open biopsy. This observation proves the possibility of damage to the skeleton due to amyloid deposition and justifies the need to include AL-amyloidosis in the spectrum of differential diagnosis of diseases that occur with osteodestructive syndrome.

Sign in / Sign up

Export Citation Format

Share Document