scholarly journals The Association of International Staging System (ISS) Stage with Disease and Symptom Burden in Patients with Newly Diagnosed Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2115-2115
Author(s):  
Mark A Fiala ◽  
Michael Slade ◽  
Jesse Keller ◽  
Keith Stockerl-Goldstein ◽  
Michael Tomasson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Performance Status ◽  
Symptom Burden ◽  
Staging System ◽  
Stage I ◽  
Stage Iii ◽  
Newly Diagnosed ◽  
Bone Marrow Plasma ◽  
International Staging System

Abstract Background: The clinical presentation of multiple myeloma (MM) varies greatly but often includes bone pain, anemia, renal dysfunction, hypercalcaemia, and/or constitutional symptoms. There are no signs or symptoms that are disease specific. The earliest staging system for MM, the Durie-Salmon (DS), associated disease and symptom burden with prognosis; however, it has been largely replaced by the International Staging System (ISS), which is easier to compute and better identifies patients with the poorest prognosis. It is unclear if ISS stage, like DS, is associated with disease or symptom burden. Objective: To compare disease and symptom burden of patients with newly diagnosed MM by ISS Stage. Methods: Data was extracted from the open-access Multiple Myeloma Research Foundation (MMRF) Researcher Gateway corresponding with interim analysis 6 from the CoMMpass study. The CoMMpass study is enrolling 1000 newly diagnosed MM patients who will be tracked longitudinally for 5 years. CoMMpass collects relevant clinical data and patient reported quality of life (EORTC QLQ-C30 and QLQ-MY20), as well as sequential tissue samples. Eligibility requirements for CoMMpass include: symptomatic MM with measureable disease by SPEP (≥1.0g/dL), UPEP (≥200mg/24 hours), or SFLC (≥10mg/dL); receiving an immunomodulator and/or a proteasome inhibitor for initial MM treatment; and no prior malignancies in the past 5 years. All clinical data was reported by trained data analysts at the enrolling center with the exception of flow cytometry which was performed centrally; raw lab values for beta-2 microglobulin and albumin were entered and stage was subsequently calculated by the analysts for this study according to the ISS (Greipp et al, JCO 2005). Twenty-six patients with unknown ISS were excluded from the analysis. Data was analyzed using SPSS 21. Categorical variables were compared using χ2, continuous with one-way ANOVA tests. Results: 599 patients were eligible for analysis. Sex, race, and heavy and light chain isotypes were all evenly distributed among the ISS stages; however, median age for ISS stage III was 67, 65 for stage II and 62 for stage I (p<0.001). Stage I and II patients were similar in disease burden, but stage III patients had higher serum M-proteins (p<0.001), LDH (p=0.002), bone marrow plasma cells (p<0.001), circulating plasma cells (p<0.001), and creatinine (p<0.001), and lower hemoglobin (p<0.001) and platelets (p=0.001). Further, stage III patients had poorer performance status (p<0.001), global health (p<0.001), physical functioning (p<0.001), social functioning (p<0.001), and role functioning (p<0.001), and increased fatigue (p<0.001) and pain (p=0.016). Results are summarized in Table 1. Conclusions: Stage III had a higher disease and symptom burden than stage I and II patients. Stage I and II patients were similar in most measures suggesting that ISS may not discriminate between these groups well, this is supported by other studies that have failed to find outcomes differences between stage I and II patients. Table 1. Stage I n= 204 Stage II n = 210 Stage IIIn = 185 p Demographics Age in years 62 65 67 <0.001 Male 64% 57% 62% NS Race NS White 80% 83% 74% Black 19% 13% 23% Other 2% 3% 3% Heavy Chain NS IgG 80% 80% 75% IgA 20% 20% 25% Light Chain NS Kappa 65% 61% 60% Lambda 34% 38% 38% Biclonal 1% 2% 2% Disease Burden Serum M-Protein g/dL 1.9 2.0 3.2 <0.001 LDH μkat/L 2.7 2.8 3.0 0.002 Bone Marrow Plasma Cells* 7% 9% 13% <0.001 Circulating Plasma Cells* 0% 0% 0.1% <0.001 Calcium mmol/L 2.4 2.3 2.4 <0.001 Creatinine μmol/L 82 88 149 <0.001 Hgb mmol/L 7.4 6.4 5.8 <0.001 Platelets x109/L 222 212 199 .001 Bone Lesions 61% 52% 53% NS Symptom Burden/Quality of Life Measures ECOG Performance Status <0.001 0 47% 42% 22% 1 49% 42% 54% 2 5% 8% 15% 3-4 0% 8% 9% Global Health Scale 66 66 50 <0.001 Physical Functioning Scale 86 80 63 <0.001 Cognitive Functioning Scale 83 83 83 NS Emotional Functioning Scale 75 75 75 NS Social Functioning Scale 83 83 66 <0.001 Role Functioning Scale 66 66 50 <0.001 Disease Symptom Scale 27 22 27 NS Fatigue Scale 33 33 44 <0.001 Pain Scale 33 33 42 0.016 Note-Median presented unless specified. *- CD38+/CD138+ by flow cytometry Disclosures Vij: Takeda, Onyx: Research Funding; Celgene, Onyx, Takeda, Novartis, BMS, Sanofi, Janssen, Merck: Consultancy.

scholarly journals Early mortality in elderly patients undergoing treatment for multiple myeloma in real-world practice

2018 ◽  
Vol 46 (6) ◽  
pp. 2230-2237
Author(s):  
Jun Xia ◽  
Lingling Wang ◽  
Xin Zhou ◽  
Jing Wang ◽  
Huan Wang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Lactate Dehydrogenase ◽  
Elderly Patients ◽  
Real World ◽  
Staging System ◽  
Early Mortality ◽  
Stage Iii ◽  
Newly Diagnosed ◽  
International Staging System ◽  
High Lactate

Objectives This study was performed to analyze the risk factors for early mortality (EM) in elderly patients undergoing treatment for multiple myeloma (MM) in real-world clinical practice. Methods Retrospective data from 108 elderly patients who were newly diagnosed with MM from January 2007 to July 2015 were analyzed in a single hematology center. EM was defined as death of any cause within 12 months after diagnosis. A multivariate regression model was used to evaluate EM. Results EM occurred in 16 (14.8%) elderly patients with newly diagnosed MM. The most common cause of death was infection (10/16, 62.5%). In the multivariate analysis, only an age of ≥75 years, International Staging System (ISS) stage III disease, and high lactate dehydrogenase concentration were significantly and independently associated with EM. Conclusion Our results suggest that infection is the leading cause of EM in elderly patients with MM. An age of ≥75 years, ISS stage III disease, and a high lactate dehydrogenase concentration are significant predictors of EM. We should further target this higher-risk patient population to define personalized therapy with which to improve outcomes.

Validation of International Staging System (ISS) for Multiple Myeloma: A Retrospective Analysis of 487 Patients at 8 Brazilian Centers.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5069-5069
Author(s):  
Vania T.M. Hungria ◽  
Angelo Maiolino ◽  
Gracia Martinez ◽  
Gisele Colleoni ◽  
Luciana Oliveira ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Factors ◽  
Median Survival ◽  
Staging System ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
High Dose ◽  
International Staging System ◽  
New System

Abstract Introduction: The survival of patients with multiple myeloma varies from a few months to more than 10 years. This heterogeneity is related to the characteristics of the myeloma itself and of the host. The identification of the factors which influence the prognosis is very important to predict the result, assist in the choice of the treatment and adequately stratify the patients in clinical studies. Many prognostic factors have been identified in patients with multiple myeloma, such as anemia, renal failure, ß2 microglobulin, albumin and chromossomic alterations. Some authors have combined prognostic factors and proposed various systems of staging. However, none of them have yet substituted the Durie-Salmon staging system. Recently, the International Myeloma Working Group, with the objective of developing a simple and reliable staging system, which can be internationally applied to classify and stratify patients with multiple myeloma, identified 3 risk groups. This new system of staging, the “International Staging System” (ISS), consists of stage I: ß2 microglobulin &lt; 3.5 mg/L plus albumin ≥ 3.5 g/dL (median survival: 62 months); stage II: neither I nor III (median 44 months); stage III: ß2 microglobulin &gt; 5.5 mg/L (median 29 months). This study included sites in North America, Europe and Asia, but the sites in Latin America were not included. Objective: To validate the ISS in patients with multiple myeloma at Brazilian centers. Patients and Methods: Four hundred and eighty-seven patients with the diagnosis of multiple myeloma within the period of 1998 to 2004 at Santa Casa de São Paulo, Hospital Universitário Clementino Fraga Filho do Rio de Janeiro, Hospital das Clínicas de São Paulo, Hospital São Paulo, Hospital das Clínicas de Ribeirão Preto, HEMOPE, Hospital Prof. Edgar Santos de Salvador and Hospital de Clínicas de Porto Alegre, with available data on albumin and ß2 microglobulin, were stratified according to the ISS. A total of 339 patients received standard therapy and 148 received high-dose therapy as initial therapy. The survival was estimated using the Kaplan-Meier method with differences in survival examined using the logrank test. Results: The median age of the patients was 60 years, 52% male and 48% female. In Stage I (n=104), the global median survival was not reached, the survival at 60 months was 60%, in stage II (n=264), the global median survival was 61 months and in stage III (n=119), 19 months (p&lt;0.001). Conclusion: The new system of staging for multiple myeloma (ISS) is simple, based on variables easy to be applied and was possible to be validated in patients with multiple myeloma in Brazilian centers.

The Role of Cytokines, Growth and Angiogenic Factors in Patients with NEWLY Diagnosed Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4997-4997
Author(s):  
Gurhan Kadikoylu ◽  
Hakan Dogan ◽  
Mukadder Serter ◽  
Aslihan Karul ◽  
Ibrahim Meteoglu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Growth Factor ◽  
Staging System ◽  
Angiogenic Factors ◽  
Stage I ◽  
Stage Iii ◽  
Control Group ◽  
Newly Diagnosed

Abstract Abstract 4997 The cytokines such as interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-a may play some roles in both the pathogenesis of multiple myeloma (MM) and bone destruction. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and angiopoietin (Ang)-2 in recent years may trigger angiogenesis in MM. Moreover transforming growth factor (TGF)-β and insulin-like growth factor (IGF)-1 induce angiogenesis and proliferation of myeloma cells. In this prospective study, we investigated the role of cytokines, growth and angiogenic factors in patients with newly diagnosed MM. Fifty patients (32 were male and 18 female, with mean age of 63 ± 11 years) with newly diagnosed MM were enrolled to this study. Local ethical commity of our university approved this study. 30 healthy individuals (12 were male and 8 female, with mean age of 55±9 years) were selected as control group. The exclusion criteria were malignancy, acute and chronic infections, autoimmune disorders, diabetes mellitus, immune deficiency, and chronic inflammatory diseases. According to Durie-Salmon staging system, 10%, 22%, and 68% of the patients with MM were in Stage I, Stage II and Stage III, respectively. 17%, 44%, and 39% of patients with MM were in International prognostic index-1 (IPI1), IPI2, and IPI3, respectively. 90% of the patients were symptomatic MM, 6% of them were smoldering MM, and solitary plasmacytoma was detected in 4% of the patients. The levels of IL-1β, IL-2, IL-6, IL15, TNF-a, VEGF, bFGF, TGF-β, HGF, IGF-1, Ang-1 and Ang-2 were determined using ELISA in patients and controls. VEGF and nuclear factor kappa-B (NFkB) were evaluated as immunohistochemistry in bone marrow biopsy in patients and pathological control group (13 were male and 6 female, with mean age of 64±14 years) with non-Hodgkin's lymphoma and without bone marrow involvement. In this study, the levels of IL-1β (p<0. 001), IL-2 (p<0. 001), IL-6 (p<0. 001), TNF-a (p<0. 001), IGF-1 (p<0. 001), TGF-β (p<0. 001), HGF (p=0. 004), and Ang-2 (p<0. 001) in patients were higher than controls. But there was no difference for Ang-1, IL-15, and VEGF in between two groups (p>0. 05). According to immunohistochemistry scoring, while NFkB scores in patients were higher than controls (p=0. 035), any significance was not detected for VEGF in between patient and pathological control groups (p>0. 05). According to Durie-Salmon staging system, TNF-a levels in Stage I were higher than Stage III (p=0. 035). According to IPI, TGF-β levels in patients with IPI-1 were higher than the patients with IPI-2 (p=0. 017) and IPI-3 (p=0. 003). The pathogenesis of MM is stil unclear. In this study, although VEGF did not increase, increment in the levels of Ang-2 and other growth factors indicated the induction of angiogenesis in MM. In earlier stage, this condition may be apparent. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Role of18F-FDG PET/CT in Multiple Myeloma Staging according to IMPeTUs: Comparison of the Durie–Salmon Plus and Other Staging Systems

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Shengming Deng ◽  
Bin Zhang ◽  
Yeye Zhou ◽  
Xin Xu ◽  
Jihui Li ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Prognostic Factors ◽  
Staging System ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Newly Diagnosed ◽  
Deauville Score ◽  
Staging Systems

We aimed at comparing the Durie–Salmon Plus (DS Plus) staging system based on Italian Myeloma criteria for PET USe (IMPeTUs) with other two staging systems in predicting prognosis of patients with all stages of newly diagnosed multiple myeloma (MM). A total of 33 MM patients were enrolled in this retrospective study. The variation between the DS Plus classification and Durie–Salmon staging system (DSS) or Revised International Staging System (RISS) classification was assessed. When staged by the DSS, patients in stage I and stage II did not reach the median overall survival (OS), and the median OS was 33 months for stage III (p=0.3621). When staged by the DS Plus, patients in stage I did not reach the median OS of stage I, and the median OS for stages II and III was 38 and nine months, respectively (p=0.0064). When staged by the RISS, patients in stage I did not reach the median OS, and the median OS was 33 and 16 months for stage II and stage III, respectively (p=0.0319). The concordances between two staging systems were 0.07 (DS Plus versus DSS) and 0.37 (DS Plus versus RISS), respectively. Multivariate analysis revealed that DS Plus stage III (HR: 11.539,p=0.021) and the Deauville score of bone marrow ≥4 (HR: 3.487,p=0.031) were independent prognostic factors associated with OS. Both the DS Plus based on IMPeTUs and RISS possessed a better potential in characterizing and stratifying MM patients compared with the DSS. Moreover, DS Plus stage III and the Deauville score of bone marrow ≥4 were reliable prognostic factors in newly diagnosed MM patients.

Prognostic factors in multiple myeloma: definition of risk groups in 410 previously untreated patients: a Grupo Argentino de Tratamiento de la Leucemia Aguda study.

1989 ◽  
Vol 7 (12) ◽  
pp. 1839-1844 ◽  
Author(s):  
C Corrado ◽  
M T Santarelli ◽  
S Pavlovsky ◽  
M Pizzolato
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Renal Function ◽  
Prognostic Factors ◽  
Plasma Cells ◽  
Performance Status ◽  
Univariate Analysis ◽  
Staging System ◽  
Risk Groups ◽  
Bone Marrow Plasma

Four hundred ten previously untreated multiple myeloma patients entered onto two consecutive Grupo Argentino de Tratamiento de la Leucemia Aguda (GATLA) protocols were analyzed to identify significant prognostic factors influencing survival. The univariate analysis selected the following variables: performance status, renal function, percentage of bone marrow plasma cells at diagnosis, hemoglobin, and age. A multivariate analysis showed that performance status, renal function, percentage of bone marrow plasma cells, hemoglobin, and age were the best predictive variables for survival. A score was assigned to each patient according to these variables, which led to their classification in three groups: good, intermediate, and poor risk, with a probability of survival of 26% and 10% at 96 months, and 5% at 56 months, and median survival of 60, 37, and 14 months, respectively (P = .0000). In our patient population, this model proved to be superior to the Durie-Salmon staging system in defining prognostic risk groups, and separating patients with significantly different risks within each Durie-Salmon stage.

Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome

Blood ◽  
2007 ◽  
Vol 109 (8) ◽  
pp. 3489-3495 ◽  
Author(s):  
Hervé Avet-Loiseau ◽  
Michel Attal ◽  
Philippe Moreau ◽  
Catherine Charbonnel ◽  
Frédéric Garban ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Plasma Cells ◽  
Treatment Strategies ◽  
Staging System ◽  
Hematologic Malignancies ◽  
Therapeutic Trials ◽  
Bone Marrow Plasma ◽  
Genomic Aberrations ◽  
International Staging System ◽  
Chromosomal Changes

Abstract Acquired genomic aberrations have been shown to significantly impact survival in several hematologic malignancies. We analyzed the prognostic value of the most frequent chromosomal changes in a large series of patients with newly diagnosed symptomatic myeloma prospectively enrolled in homogeneous therapeutic trials. All the 1064 patients enrolled in the IFM99 trials conducted by the Intergroupe Francophone du Myélome benefited from an interphase fluorescence in situ hybridization analysis performed on purified bone marrow plasma cells. They were systematically screened for the following genomic aberrations: del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p). Chromosomal changes were observed in 90% of the patients. The del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p) were present in 48%, 21%, 14%, 39%, 13%, and 11% of the patients, respectively. After a median follow-up of 41 months, univariate statistical analyses revealed that del(13), t(4;14), nonhyperdiploidy, and del(17p) negatively impacted both the event-free survival and the overall survival, whereas t(11;14) and MYC translocations did not influence the prognosis. Multivariate analyses on 513 patients annotated for all the parameters showed that only t(4;14) and del(17p) retained prognostic value for both the event-free and overall survivals. When compared with the currently used International Staging System, this prognostic model compares favorably. In myeloma, the genomic aberrations t(4;14) and del(17p), together with β2-microglobulin level, are important independent predictors of survival. These findings have implications for the design of risk-adapted treatment strategies.

Impact of Serum Albumin and B2-Microglobulin level on 2-Year Overall Survival among Newly Diagnosed Multiple Myeloma Patients: A retrospective Study

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Sherian Salama ◽  
Rodaina Yousef ◽  
Asma Al Olama ◽  
Mahmoud Marashi ◽  
Hana Salama ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Serum Albumin ◽  
United Arab Emirates ◽  
Staging System ◽  
Albumin Level ◽  
Age At Diagnosis ◽  
Newly Diagnosed ◽  
International Staging System ◽  
Beta 2 ◽  
Beta 2 Microglobulin

Background: Multiple myeloma accounts for 1% of all cancers and approximately 10% of all hematologic malignancies. Evaluation and initial staging of the disease is made once the diagnosis is confirmed. The recommended staging system is the International Staging System (ISS). Which determines the Myeloma prognosis by 2 factors: beta-2 Microglobulin and Serum albumin. Goal and Objective: The main goal of this study is to assess the effect of Beta-2 microglobulin and Serum albumin on patient’s survival rate with Multiple Myeloma. The secondary objective is to compare the age at diagnosis with other literature. Methodology: The current study was carried out in Hematology Unit, Dubai Hospital, Dubai, Dubai Health Authority (DHA), United Arab Emirates. Chart review was done retrospectively for 49 newly diagnosed patients with Multiple Myeloma diagnosed between the period 2012-2016. Purposive sample was used to those patients who met the inclusion criteria of this study, to be diagnosed and treated in DH. diagnosed and received regular treatment in Dubai Hospital. Results: Medina follow-up of the patients in this study was (12.8) months. The 2-year overall survival rate for patients with Multiple Myeloma (n = 49) was approximately 80%. While, the 2-year OS rate based on Albumin level. Patients with albumin level > 3.5 mg\dl was significantly higher compared to those who had an albumin level <3.5 mg\dl. 100%, 65% respectively, P = 0.033. Moreover, the 2-year OS rate in terms B2MG level. Patients who had a B2MG < 3.5 mg\dl OS was slightly higher compared to those who had (3.5-5.5 and 5.5 mg\dl). OS rate approximately 85 %, 80 % and 75 respectively, P = .737 Conclusion: Multiple myeloma (MM) is a very heterogeneous disease. For this reason, various prognostic factors and staging systems have been developed to predict the disease outcome. International Staging System (ISS) is very useful in determine the survival based on serum β2- microglobulin and serum albumin levels. The age at diagnosis in Dubai hospital, United Arab Emirates is much younger compared to other studies conducted worldwide. The sample used in the study was also highly diverse in terms of culture and nationality. Such diversity is largely typical in Gulf especially in United Arab Emirates. Therefore, this can play important role in age at diagnosis.

High Expression Levels of Long Noncoding RNA Small Nucleolar RNA Host Gene 18 and Semaphorin 5A Indicate Poor Prognosis in Multiple Myeloma

2019 ◽  
Vol 143 (3) ◽  
pp. 279-288 ◽  
Author(s):  
Ling-Juan Huang ◽  
Ying Shen ◽  
Ju Bai ◽  
Fang-Xia Wang ◽  
Yuan-Dong Feng ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Noncoding Rna ◽  
Poor Prognosis ◽  
Clinical Characteristics ◽  
Staging System ◽  
High Expression ◽  
Newly Diagnosed ◽  
High Expression Group ◽  
International Staging System ◽  
Nucleolar Rna

Background: The aim of this study was to detect the expression of long noncoding RNA small nucleolar RNA host gene 18 (SNHG18) andsemaphorin 5A (SEMA5A) genes in multiple myeloma (MM) patients and to explore the correlation of the expression of these genes with the clinical characteristics and prognosis of MM patients. Methods: Forty-seven newly diagnosed MM, 18 complete remission MM, 13 refractory/relapse MM, and 22 iron deficiency anemia (serving as control) samples were extracted at the Department of Hematology, Second Affiliated Hospital of Xian Jiaotong University between January 2015 and December 2016. The clinical features of the MM patients are summarized. Real-time quantitative PCR was performed to analyze the relative expression levels of the SNHG18 and SEMA5Agenes. The clinical characteristics and overall survival (OS) of the MM patients were statistically analyzed while measuring different levels of SNHG18 and SEMA5Agene expression. At the same time, the correlation between the expression of SNHG18 and SEMA5A was also analyzed. Results: The analysis confirmed that SNHG18 and its possible target gene SEMA5A were both highly expressed in newly diagnosed MM patients. After analyzing the clinical significance of SNHG18 and SEMA5A in MM patients, we found that the expression of SNHG18 and SEMA5A was related to the Durie-Salmon (DS), International Staging System (ISS), and Revised International Staging System (R-ISS) classification systems, and the Mayo Clinic Risk Stratification for Multiple Myeloma (mSMART; p < 0.05). Moreover, we observed a significant difference in OS between the SNHG18/SEMA5A high expression group and the low expression group. We found a positive correlation between SNHG18 and SEMA5A expression (r = 0.709, p < 0.01). Surprisingly, the expected median OS times of both the SNHG18 and SEMA5Ahigh expression groups were significantly decreased, which was in contrast to those of both the SNHG18 and SEMA5Alow expression groups and the single-gene high expression group (p < 0.05). Conclusion: High expression of both SNHG18 and SEMA5A is associated with poor prognosis in patients with MM.

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