Increase of novel biomarkers for oxidative stress in patients with plasma cell disorders and in multiple myeloma patients with bone lesions

2012 ◽  
Vol 61 (10) ◽  
pp. 1063-1067 ◽  
Author(s):  
Sebastiano Gangemi ◽  
Alessandro Allegra ◽  
Andrea Alonci ◽  
Mariateresa Cristani ◽  
Sabina Russo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Myeloma ◽  
Plasma Cell ◽  
Bone Lesions ◽  
Plasma Cell Disorders ◽  
Novel Biomarkers ◽  
Biomarkers For Oxidative Stress

Clinical implication of PET/CT and skeletal bone survey in evaluation of multiple myeloma and related monoclonal disorders.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18574-e18574
Author(s):  
Muhammad Jawad Popalzai ◽  
Homam Alkaied ◽  
Maryah Mansoor ◽  
Arnold Brenner ◽  
Qun Dai
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Skeletal Survey ◽  
Whole Body ◽  
Bone Lesions ◽  
Positive Finding ◽  
Pet Ct ◽  
Plasma Cell Disorders ◽  
Smoldering Myeloma

e18574 Background: Whole body skeletal x-ray is considered a gold standard for detecting bone lesions in patients with plasma cell disorders. PET/CT has been increasingly used but its role is yet to be defined. We conducted this study to compare the role of these two imaging modalities in evaluation of plasma cell disorders. Methods: This is single institution, retrospective study to evaluate the role of skeletal survey and PET/CT in patients with multiple myeloma, smoldering myeloma and MGUS. Patients’ records, imaging reports and subsequent management plan were reviewed and compared. Results: A total of 16 patients were reviewed. Among them, 11 patients had multiple myeloma, 2 had smoldering myeloma, and 3 had MGUS. 7/11 patients with multiple myeloma had concordant findings on skeletal survey and PET. 3 of these patients had negative skeletal surveys but had positive finding on PET/CT. PET/CT also identified plasmacytomas in 2 patients. In 2 patients with smoldering myeloma, both skeletal survey and PET/CT were negative. 2/3 patients with MGUS had lytic lesions on skeletal surveys which were not revealed by subsequent PET/CT’s. Both patients were observed without treatment and at 2 years follow up did not show disease progression. Conclusions: Our retrospective analysis showed that skeletal survey is still important for base-line evaluation of bone lesions in multiple myeloma and related monoclonal disorders. PET/CT is more sensitive for detection of bone lesions and can also detect extraosseous lesions such as plasmacytomas. Using tumor metabolic activity, PET/CT may improve diagnostic accuracy and is complementary to conventional skeletal survey. [Table: see text]

scholarly journals Levels of CEACAM6 in Peripheral Blood Are Elevated in Patients with Plasma Cell Disorders: A Potential New Diagnostic Marker and a New Therapeutic Target?

2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
N. Steiner ◽  
R. Hajek ◽  
D. Nachbaur ◽  
B. Borjan ◽  
S. Sevcikova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Adhesion Molecule ◽  
Peripheral Blood ◽  
Therapeutic Target ◽  
Plasma Levels ◽  
Diagnostic Marker ◽  
Healthy Controls ◽  
Plasma Cell Disorders

Introduction. The prognosis of multiple myeloma is still unfavorable due to inherent characteristics of the disease and the often-delayed diagnosis due to widespread and unspecific symptoms such as back pain and fatigue. Therefore, a simple diagnostic blood test would be helpful to speed up the diagnostic procedure in such patients (pts.). Here, we evaluated the diagnostic value of plasma levels of carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) in the peripheral blood and bone marrow of pts. with plasma cell disorders and in healthy controls. Materials and Methods. Immunoreactive CEACAM6 was determined in the peripheral blood and bone marrow (n=95/100) of pts. with monoclonal gammopathy of unknown significance (MGUS: 28/37), newly diagnosed multiple myeloma (NDMM: 42/40), and relapsed/refractory multiple myeloma (RRMM: 25/23) by sandwich ELISA. Results. Median CEACAM6 levels in the peripheral blood of pts. with plasma cell disorders were significantly higher than those of healthy controls (healthy controls: 15.2 pg/ml (12.1-17.1); MGUS: 19.0 pg/ml (16.4-22.5); NDMM: 18.0 pg/ml (13.4-21.2); and RRMM: 18.9 pg/ml (15.2-21.5); p<0.001). Plasma levels of CEACAM6 discriminated healthy subjects from MGUS/NDMM pts. (AUC=0.71, 95% CI: 0.6-0.8); i.e., a CEACAM6 level>17.3 pg/ml has an 82% (95% CI: 70-90) predictive probability for the identification of MGUS or NDMM. Moreover, CEACAM6 levels in the bone marrow were significantly higher in RRMM pts. than in NDMM pts. (p=0.04), suggesting a role of this molecule in disease progression. Conclusion. CEACAM6 plasma levels can noninvasively identify pts. with a plasma cell disorder and should be evaluated prospectively as a potential diagnostic marker. Moreover, due to high CEACAM6 levels in the bone marrow in RRMM pts., this adhesion molecule might be a therapeutic target in multiple myeloma pts.

scholarly journals Enumeration and characterization of circulating multiple myeloma cells in patients with plasma cell disorders

2017 ◽  
Vol 180 (1) ◽  
pp. 71-81 ◽  
Author(s):  
Brad Foulk ◽  
Mike Schaffer ◽  
Steve Gross ◽  
Chandra Rao ◽  
Denis Smirnov ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Myeloma Cells ◽  
Plasma Cell Disorders

scholarly journals Tracking Daratumumab Clearance Using Mass Spectrometric Approaches: Implications on M Protein Monitoring and Reusing Daratumumab

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2707-2707
Author(s):  
Nadine Abdallah ◽  
David L Murray ◽  
Angela Dispenzieri ◽  
Prashant Kapoor ◽  
Morie A. Gertz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Plasma Cell ◽  
Research Funding ◽  
Univariate Analysis ◽  
M Protein ◽  
Urine Protein ◽  
Advisory Committees ◽  
Plasma Cell Disorders

Abstract Background: MASS-FIX is a screening method for serum and urine monoclonal proteins in multiple myeloma and related plasma cell disorders, which uses immunoglobulin enrichment coupled with matrix-assisted laser desorption ionization time-of-flight mass-spectrometry (MALDI-TOF). In addition to superior sensitivity over conventional gel-based techniques, MASS-FIX can distinguish therapeutic monoclonal antibodies (MoAb) from patient's M protein. As the utilization of therapeutic MoAbs increases, it is essential to understand the persistence pattern of these therapeutic antibodies in the serum. We designed this study to evaluate the duration of daratumumab detection by MASS-FIX in the serum of treated patients. Methods: We used a prospectively maintained database at Mayo clinic to identify patients with multiple myeloma and related plasma cell disorders who were treated with a daratumumab-containing regimen anytime during their disease course and had serial MASS-FIX data available after discontinuation of daratumumab. A univariate analysis was performed to assess for factors that may impact the clearance of daratumumab. Results: We included 125 patients with plasma cell disorders who received daratumumab as first or subsequent line of treatment between March 15 th, 2016, and March 4 th, 2020. The median age was 60.2 years and 57% were male. The most common diagnoses were multiple myeloma (70%) and light chain amyloidosis (18%). Daratumumab-based treatments were initiated after a median of 28.8 (IQR: 6.4-76.3) months from initial diagnosis. The most common regimen used was daratumumab, bortezomib and dexamethasone (23%); 26% underwent transplant after daratumumab-based induction. The median duration of treatment with a daratumumab-based regimen was 208 (IQR: 99-479) days. The median follow-up from the time of daratumumab discontinuation was 457 (95% CI: 346-NR) days. By last follow up, daratumumab was not detected by MASS-FIX in 93 (74%) patients but remained detectable in 32 (26%) patients. The median time from daratumumab discontinuation to disappearance of daratumumab by MASS-FIX was 160 (IQR: 107-233) days. On univariate analysis, the presence of ≥0.5 grams of urine protein was associated with earlier disappearance of daratumumab on MASS-FIX [risk ratio (RR): 2.0, P=0.02). The median time from daratumumab discontinuation to disappearance of daratumumab on MASS-FIX was 116 (95%CI: 76-160) days in patients with urine protein ≥0.5 grams and 203 (95%CI: 162-216) days in patients with urine protein &lt;0.5 grams (P=0.02). There was no association between the time to disappearance of daratumumab by MASS-FIX and old age ≥70 (RR: 0.9, P=0.81], male gender (RR: 0.9, P=0.60), eGFR &lt;60 (RR: 1.0, P=0.98), daratumumab schedule (every 1/2 weeks vs &gt;2weeks) (RR: 1.0, P=0.97), treatment duration (&lt;200 days vs ≥200 days) ( RR: 1.0, P=0.95), or transplantation status (RR: 1.0, P=0.98). Conclusion: The therapeutic monoclonal antibody daratumumab remains detectable in the serum of treated patients by MASS-FIX for several months after discontinuation and the duration varies between individual patients. This data has implications for diagnostic and monitoring testing and may provide guidance for reuse of daratumumab in clinical trials and practice. Proteinuria is associated with earlier disappearance of daratumumab by MASS-FIX and may have implications in patients with amyloidosis and monoclonal immunoglobulin deposition disease (MIDD). Further studies are needed to identify additional factors associated with the timing of disappearance. Disclosures Murray: Mayo Clinic: Other: Has received patents for the Mass-Fix technology which has been licensed to the Binding Site with potential royalties.. Dispenzieri: Takeda: Research Funding; Alnylam: Research Funding; Pfizer: Research Funding; Oncopeptides: Consultancy; Sorrento Therapeutics: Consultancy; Janssen: Consultancy, Research Funding. Kapoor: Karyopharm: Consultancy; Cellectar: Consultancy; BeiGene: Consultancy; Pharmacyclics: Consultancy; Sanofi: Consultancy; Amgen: Research Funding; Ichnos Sciences: Research Funding; Regeneron Pharmaceuticals: Research Funding; Glaxo SmithKline: Research Funding; Karyopharm: Research Funding; Sanofi: Research Funding; Takeda: Research Funding; AbbVie: Research Funding. Gertz: Akcea Therapeutics, Ambry Genetics, Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Karyopharm Therapeutics, Pfizer Inc (to Institution), Sanofi Genzyme: Honoraria; Ionis Pharmaceuticals: Other: Advisory Board; Akcea Therapeutics, Alnylam Pharmaceuticals Inc, Prothena: Consultancy; Aurora Biopharma: Other: Stock option; AbbVie Inc, Celgene Corporation: Other: Data Safetly & Monitoring. Dingli: Alexion: Consultancy; Novartis: Research Funding; Apellis: Consultancy; Janssen: Consultancy; Sanofi: Consultancy; GSK: Consultancy. Kumar: Antengene: Consultancy, Honoraria; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bluebird Bio: Consultancy; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Merck: Research Funding; Roche-Genentech: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Beigene: Consultancy; Oncopeptides: Consultancy; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Research Funding; Carsgen: Research Funding; Tenebio: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding.

scholarly journals Plasma Cell Dyscrasias in HIV, Epidemiology, Presentation and Treatment Characteristics and Its Strong Association with Hepatitis C- Report Form a Large HIV Cohort

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5607-5607
Author(s):  
Nishi Shah ◽  
Sakshi Jasra ◽  
Ana Acuna-Villaorduna ◽  
Urvi A Shah ◽  
Gurbakhash Kaur ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Retrospective Study ◽  
Plasma Cell ◽  
Heavy Chain ◽  
Autologous Transplantation ◽  
Bone Lesions ◽  
Cell Transplant ◽  
Hiv Diagnosis ◽  
Plasma Cell Dyscrasias ◽  
Successful Outcomes

Abstract Introduction: As people with HIV live longer, the epidemiology of plasma cell disorders (PCD) including MGUS, smoldering myeloma and Multiple myeloma (MM) becomes relevant and remains unknown. Moreover, patients with HIV have a higher incidence of monoclonal proteins which may not be related to an underlying lymphoproliferative disorder[1, 2] . There are mostly anecdotal reports and very few studies in HIV myeloma[3]. A retrospective study of 10 patients with HIV+ve symptomatic MM reported possible therapeutic benefit of ART and reported better overall survival of HIV+ve MM on ART as compared to HIV -ve MM. There is a paucity of data in PCD in this population whose incidence can be expected to increase globally. We conducted a single-institution retrospective study to look at the incidence of PCD. Methodology:We reviewed an electronic database of patients with HIV related PCD treated at Montefiore Medical Center between 2001 and 2018. All patients with a new diagnosis of PCD between January 1 2001 to July 15 2018 were identified. Data on patient demographics, HIV status, clinical outcomes (including mortality) and therapy was collected. Results: Between 2001 and 2018, 14438 patients were identified with HIV and 1986 patients had a monoclonal band in SPEP (13.8%). Based on our previous study, patients who had a definitive monoclonal band or suspected MM underwent a BM biopsy. 34 patients were diagnosed with PCD --MGUS 16 (47.05%), Smoldering MM 1 (2.94%), MM 16 (47.05%) and Primary plasma cell leukemia (PCL) 1 (2.94%). The majority of the patients were AA consistent with demographics of the Bronx. Interestingly HCV co-infection was identified in 50% (n=17) of patients and HBV co-infection was present in 15% (n=5) patients. The median CD4 count was 381 (12-1080), median viral load 237 (0-501534) and 53% patients were on ART at the time of diagnosis. The median time from HIV diagnosis was 13.9 (-2.8 to 29) years. In patients with MGUS the predominant heavy chain involvement was IgG, the median protein on SPEP was 1.1 g (0.7-1.9 g) and percentage of BM involvement was 5% (2-10%). In patients with MM IgG was the predominant heavy chain involved. On presentation, ISS Stage was Stage I in 2 patients (15.4%), 4 (30.7%) had at least Stage 2, 7 patients (53.9%) had stage 3. On presentation, 10 (58.8%) patients presented with anemia, 10 (58.8%) presented with renal impairment (Cr>=1.3), 16 (94.1%) presented with bone lesions, 6 (37.5%) presented with hypercalcemia. 5 patients (34.6%) had extramedullary presentation including 1 patient (2.9%) with PCL, 2 (5.8%) with anaplastic plasmacytoma. All patients were treated with an imid or bortezomib based regimen and there were no unusual side effects in these patients. 5 patients (29.4%) underwent autologous stem cell transplant with successful outcomes. Discussion: The prevalence of a positive SPEP is 13.8% in patients with HIV and the prevalence of plasma cell dyscrasias (PCD) in our population is 0.02%. A previous study from this cohort[2] showed that approximately 6.4% of patients with a positive SPEP developed hematological malignancy and all patients with a faint monoclonal band had lymphoma (70.5%) and those with a definite monoclonal band had myeloma (29.5%). Even though prevalence is less than the general population rate of 3%, as patients with HIV live longer this number may increase. In our study there was a high rate of co-infection with HCV in patients who had a PCD and this needs further investigation to determine causality. PCD developed at a median of 13.9 years after HIV diagnosis. The ISS staging distribution in patients presenting with myeloma is consistent with non HIV myeloma. People with HIV tolerate standard imid or proteasome inhibitor based triple drug therapy and have successful outcomes with autologous transplantation. This is the largest cohort and report describing PCD in HIV population. References:Jou, E., et al., Viral co-infections and paraproteins in HIV: effect on development of hematological malignancies. Ann Hematol, 2016. 95(4): p. 575-80.Jou, E., et al., Retrospective study of the prevalence and progression of monoclonal gammopathy in HIV positive versus HIV negative patients. Hematol Oncol, 2017. 35(1): p. 64-68.Li, G., et al., A retrospective analysis of ten symptomatic multiple myeloma patients with HIV infection: A potential therapeutic effect of HAART in multiple myeloma. Leukemia Research, 2014. 38(9): p. 1079-1084. Disclosures Janakiram: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Mieloma de células plasmáticas secretor de IgD, un reto diagnóstico. Reporte de un caso

2013 ◽  
Vol 38 (4) ◽  
pp. 268-272
Author(s):  
Lina María Gaviria Jaramillo ◽  
Beatriz Cárdenas Moreno ◽  
Maria Cecilia Mondragón ◽  
Natalia María Guevara Arismendy
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Urine Analysis ◽  
Clinical Manifestations ◽  
Poor Response ◽  
Serum Levels ◽  
Final Diagnosis ◽  
Bone Lesions ◽  
Plasma Cell Myeloma ◽  
Immunoglobulin D

RESUMEN El mieloma de células plasmáticas secretor de IgD es una neoplasia de células plasmáticas poco frecuente y agresivo, generalmente afecta individuos más jóvenes que los demás mielomas. Es de difícil diagnóstico, ya que no se observa el pico de proteína monoclonal característico de los mielomas; no obstante, la inmunofijación, la cuantificación de IgD y el estudio de orina son pruebas de gran utilidad para su diagnóstico. Con respecto a las manifestaciones clínicas, es frecuente anemia, falla renal y múltiples lesiones óseas; además, la enfermedad tiene un curso agresivo, con poca respuesta a la quimioterapia convencional. A continuación, se describe un caso de una mujer de 57 años con antecedentes de dolor óseo y múltiples lesiones líticas óseas, quien fue diagnosticada con mieloma secretor de IgD a partir de la electroforesis de proteínas en suero, la inmunofijación en suero y orina, la cuantificación de IgD y el estudio medular. ABSTRACT Immunoglobulin D plasma cell myeloma is a rare and aggressive plasma cell disorder, which usually occurs in younger patients than other myelomas. Immunoglobulin D multiple myeloma is usually misdiagnosed because of the lack of a typical monoclonal protein spike; however, immunofixation electrophoresis, Immunoglobulin D serum levels and urine analysis are highly useful for diagnosis of the disease. Regarding clinical manifestations, patients commonly have anemia, renal failure, and multiple bone lesions. In addition, patients show an aggressive clinical course with poor response to conventional treatment and unfavorable prognosis. We report a 57 years-old female who presented with bone pain and multiple osteolytic bone lesions; according to serum protein electrophoresis, serum and urine immunofixation, IgD serum levels, and bone marrow biopsy, a final diagnosis of immunoglobulin D plasma cell myeloma was made. KEY WORDS Multiple myeloma, immunoglobulin D, renal insufficiency  

scholarly journals A Cross Sectional Epidemiological and Survival Analysis of All Patients with Plasma Cell Disorders Recorded between 2011- 2017 in the Social Insurance System of Turkey

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5847-5847
Author(s):  
Metin Dag ◽  
Meral Beksac
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Survival Analysis ◽  
Board Of Directors ◽  
Healthcare System ◽  
Plasma Cell ◽  
Real World ◽  
Real World Data ◽  
Advisory Committees ◽  
Plasma Cell Disorders

Abstract Background and Aim: The incidence and outcomes of patients with cancer diagnoses are reported annually as SEERs in few but not all countries. Clinical trials or myeloma group studies have documented the survival of patients with plasma cell disorders to improve with the approval of new drugs, early diagnosis and better follow-up. The outcome of patients included in clinical trials do not represent the real world data. There are two major pharma sponsored international prospective or retrospective analysis of real World data where patients from Turkey are also included (Mohty et al Clin Lymphoma Myeloma Leuk 2018 and Kumar et al. Leuk Lymphoma 2018). However the results do not confer to patients of any country in particular. According to the SGK's 2016 annual report, 98,6% of the population of Turkey is covered by the Healthcare Insurance System (SGK). Electronic data recording system (2007) and e- prescribing (2010) have been introduced to the healthcare system in Turkey. The aim of this study is to analyze and report the epidemiological features of patients who are recorded and received drugs approved and reimbursed by the Turkish Healthcare system . Patients and Methods: The study is performed following Ethical Committee approval by Ankara University and also by permission for publication from SGK. Patients recorded with the ICD of C90 between 2011-2017 and has received either of these medications: Melphalan, Thalidomide, Bortezomib, Lenalidomide, Bendamustine or high dose therapy with stem cell support(ASCT) were included in the analysis. This approach was taken to prevent false ICD entry or exclude patients with Monoclonal Gamopathy of Undetermined Significance or Smoldering Multiple Myeloma who are not being treated. Additionally patients who were privately insured or received drugs within clinical trials or compassionate/early access programs were also excluded. Patients registered earlier than 2011 were not included in the analysis to allow survival analysis. Statistical analysis were performed using the SQL, SPSS, MS Office software packages. Results: A total of 10146 patients were evaluated as eligible. Annual number of patients during the 2011-2017 period were as follows: 1168, 824, 2245, 1811, 1537, 1183, 1378. Males/females: 5655/4491, Median age of patients were constant with a minor increase from 63.8(2011) to 65.2(2017). ASCT (once or more)was received by 4060 (40%)patients. Overall survival (OS) of patients improved if diagnosed younger (Fig 1a), if they are female (Fig 1b) and received ASCT(Fig 1d). There was no OS benefit if ASCT was given more than once. Approval and reimbursement of novel drugs such as Bortezomib and Lenalidomide were achieved in 2005 and 2010 respectively. Both Carfilzomib and Pomalidomide are approved but only conditionally reimbursed since 2015 and 2016. Patients who started treatment during more recent years (after 2015)are able to survive longer than those who started earlier(Fig 1c). Conclusions: This is the first and most extensive epidemiological report for Multiple Myeloma from Turkey. It informs about annual incidence of patients eligible for treatment (approximately 1400), treatment success (OS: median 4 years) during a seven year period. Our results are supporting the survival advantage of ASCT (median 5 vs. 2 years, p=0.000) and younger age(p=0.000) plus female gender (p=.0.005). Patients who initiated treatment recently have better OS than patients starting earlier (p=0.001). More detailed survival and cost benefit analyses are aimed to be presented during the meeting. Disclosures Beksac: Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen,Janssen-Cilag,Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

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