scholarly journals Multiple Extramedullary-Bone Related and/or Extramedullary Extraosseous Are Independent Poor Prognostic Factors in Patients With Newly Diagnosed Multiple Myeloma

2021 ◽  
Vol 11 ◽  
Author(s):  
JingSong He ◽  
XiaoYan Yue ◽  
DongHua He ◽  
Yi Zhao ◽  
Yang Yang ◽  
...  

BackgroundExtramedullary (EM) lesions are common in multiple myeloma (MM) and are often related to the poor prognosis of MM but are scarcely understood.MethodsIn this retrospective study, the baseline characteristics of 357 newly diagnosed patients with extramedullary multiple myeloma (EMM) and their impact on the prognosis were analyzed. All patients received first-line treatment with bortezomib-based regimen.ResultsThe overall incidence rate of EM was 22.4%, and the detection rate of PET/CT was significantly higher than other imaging methods (P = 0.015). The cohorts consisted of 10 cases of extramedullary extraosseous (EME) and 70 cases of extramedullary-bone related (EMB), including 53 cases with single site involvement (one case with EME) and 27 cases with multiple sites (>1 site) involvement (nine cases with EME). EMM patients had high levels of hemoglobin (Hgb, ≥10 g/dl) and serum lactate dehydrogenase (LDH, >245u/L) and are inclined to early-stage revised international staging system (R-ISS). Compared to patients without EM, those with EMM had worse progression-free survival (PFS) (P = 0.014) and overall survival (OS) (P = 0.032). In addition, patients without EM and those with a single site of EMB had similar PFS and OS, while patients with multiple sites of EMB or EME and multiple sites of EMB with EME had poor PFS and OS. Multivariate analysis confirmed that multiple sites of EMB and/or EME were independent prognostic predictors affecting PFS and OS in newly diagnosed MM patients.ConclusionsThis study suggested that among patients treated with bortezomib-based regimens, multiple sites of EMB and/or EME are independent poor prognostic factors for newly diagnosed MM patients, while a single site of EMB does not affect the survival of newly diagnosed MM patients. Thus, these findings could be used as a reference for the study of EMM patients in the new drug era, but prospective clinical studies are needed to provide evidence-based data for the diagnosis and treatment of EMM.

2015 ◽  
Vol 33 (26) ◽  
pp. 2863-2869 ◽  
Author(s):  
Antonio Palumbo ◽  
Hervé Avet-Loiseau ◽  
Stefania Oliva ◽  
Henk M. Lokhorst ◽  
Hartmut Goldschmidt ◽  
...  

Purpose The clinical outcome of multiple myeloma (MM) is heterogeneous. A simple and reliable tool is needed to stratify patients with MM. We combined the International Staging System (ISS) with chromosomal abnormalities (CA) detected by interphase fluorescent in situ hybridization after CD138 plasma cell purification and serum lactate dehydrogenase (LDH) to evaluate their prognostic value in newly diagnosed MM (NDMM). Patients and Methods Clinical and laboratory data from 4,445 patients with NDMM enrolled onto 11 international trials were pooled together. The K-adaptive partitioning algorithm was used to define the most appropriate subgroups with homogeneous survival. Results ISS, CA, and LDH data were simultaneously available in 3,060 of 4,445 patients. We defined the following three groups: revised ISS (R-ISS) I (n = 871), including ISS stage I (serum β2-microglobulin level < 3.5 mg/L and serum albumin level ≥ 3.5 g/dL), no high-risk CA [del(17p) and/or t(4;14) and/or t(14;16)], and normal LDH level (less than the upper limit of normal range); R-ISS III (n = 295), including ISS stage III (serum β2-microglobulin level > 5.5 mg/L) and high-risk CA or high LDH level; and R-ISS II (n = 1,894), including all the other possible combinations. At a median follow-up of 46 months, the 5-year OS rate was 82% in the R-ISS I, 62% in the R-ISS II, and 40% in the R-ISS III groups; the 5-year PFS rates were 55%, 36%, and 24%, respectively. Conclusion The R-ISS is a simple and powerful prognostic staging system, and we recommend its use in future clinical studies to stratify patients with NDMM effectively with respect to the relative risk to their survival.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5637-5637
Author(s):  
Yahui Yuan ◽  
Yan Gu ◽  
Xiaoyan Qu ◽  
Qinglin Shi ◽  
Hua Bai ◽  
...  

Abstract 【Abstract】 Objective Multiple myeloma (MM) is a kind of plasma cell malignancy tumor with larger heterogeneity. Patient's survival varies greatly. This study retrospectively analyzed serum lactate dehydrogenase (LDH) in 107 cases of elderly MM patients, to discuss its correlation with other clinical indicators of MM and the prognostic significance. Methods 107 cases of elderly MM patients were selected from our hospital from July 2008 to January 2016 as the research objects, all of whom were above 60 years and were newly diagnosed. OLIPAS AU5400 fully automatic biochemical analyzer was used to assay serum LDH concentration, and prognosis analysis was carried out combined with patients' clinical data. On this basis, 73 cases of MM patients were given R-ISS staging. Results At primary diagnosis, about 9.4% patients had increased LDH (10/107), with the median follow-up time of 15 (1-88.5) months. Median overall survival (OS) was 52.5±6.9 months in normal LDH group, while 15.5±5.2 (months) in elevated LDH group, and there were statistically significant differences (p<0.001); Median progression free survival (PFS) was 24.0±3.5 months in normal LDH group, while 12.0±10.5 monthsin elevated LDH group, and there were statistically significant differences (p=0.008). Multiple factors analysis showed that LDH was an independent prognosis factor of elderly MM. Median OS of patients was 44 and 72 months (p=0.820) with stage II and stage III of ISS staging, while median PFS was 23 and 22 months (p=0.963); Median OS of patients was 44 and 22.5 months (p=0.308) with stage II and stage III of R-ISS staging, while median PFS was 24 and 14 months (p=0.105). Conclusions LDH is one of the important indicators for prognostic judgment of elderly MM patients. R-ISS staging based on LDH level is superior to the ISS staging system in prognostic judgment. Disclosures No relevant conflicts of interest to declare.


2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Sherian Salama ◽  
Rodaina Yousef ◽  
Asma Al Olama ◽  
Mahmoud Marashi ◽  
Hana Salama ◽  
...  

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.


2019 ◽  
Vol 143 (3) ◽  
pp. 279-288 ◽  
Author(s):  
Ling-Juan Huang ◽  
Ying Shen ◽  
Ju Bai ◽  
Fang-Xia Wang ◽  
Yuan-Dong Feng ◽  
...  

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.


2018 ◽  
Vol 46 (6) ◽  
pp. 2230-2237
Author(s):  
Jun Xia ◽  
Lingling Wang ◽  
Xin Zhou ◽  
Jing Wang ◽  
Huan Wang ◽  
...  

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.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2402-2402 ◽  
Author(s):  
Shaji Kumar ◽  
Emily Blood ◽  
Martin M. Oken ◽  
Philip R. Greipp

Abstract Background: Syndecan-1 (CD138) is a heparan sulfate bearing proteoglycan found on various epithelial cells as well as on B lineage cells depending on its stage of development. Syndecan-1 (CD138) is abundantly expressed by plasma cells, especially myeloma cells. The extra cellular domain along with the heparan sulfate side chains can be cleaved off the cell surface and can be detected in the serum as soluble syndecan. Syndecan possibly plays a multifunctional role in the biology of myeloma. It has been shown to be an independent prognostic factor in patients with multiple myeloma. It has also been shown to promote myeloma cell growth through different mechanisms. Its expression has also been suggested to correlate with bone disease in MM. Methods: In this study we studied serum levels of soluble syndecan in newly diagnosed MM patients enrolled in the Eastern Cooperative Oncology Group (ECOG) E9486 and its associated correlative laboratory clinical trial E9487. We evaluated the prognostic value of syndecan in MM and its relationship to other known prognostic factors for this disease. In addition, syndecan levels were correlated with clinical and laboratory markers of bone disease. Results: A total of 501 patients were studied and the median serum syndecan-1 was 158 ng/mL. Syndecan levels correlated positively with other prognostic factors and markers of tumor burden such as β2-microglobulin (correlation coefficient 0.3; P &lt;0.00001), labeling index (0.25; &lt;0.0001), creatinine (0.23; &lt;0.0001), soluble IL6 receptor (0.3; &lt;0.0001), BM plasma cell percentage (0.16; &lt;0.0006), and disease stage (P=0.0007). Significant differences in the overall and progression free survival was found between two groups of patient separated using the median value as cut-off. The High syndecan group had a median overall survival of 36.3 months compared to 49.3 months for the low syndecan group (P &lt; 0.0001). Similarly, the high syndecan group had progression free survival of 25.4 months compared to 33.5 months for the low syndecan group (P &lt; 0.0001). In a proportional hazards model including syndecan-1 as well as labeling index, β2M, Platelet count, IL-6R, syndecan-1 retained its prognostic value for overall survival (HR 1.3, P = 0.021). Syndecan levels were correlated with various bone markers including C-terminal telopeptide of type I collagen (ICTP), osteocalcin (OC), C-terminal type I procollagen (PICP), bone-specific alkaline phosphatase (BAP), and tartrate resistant alkaline phosphatase (TRAP) and were found to correlate only with ICTP (0.25, P &lt; 0.0001). No correlation was found between clinical markers of bone disease including presence of lytic lesions, osteoporosis and pathologic fractures on X-rays or bone pain. Conclusion: In this large study, we once again confirm the prognostic value of serum syndecan-1 levels in large group of patients with newly diagnosed myeloma. Syndecan-1 level correlates with other disease markers. Syndecan levels also correlated with ICTP, a marker of bone turnover, though no strong correlation was found between syndecan levels and clinical markers of myeloma bone disease. The biological basis of these finding needs further evaluation.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4827-4827
Author(s):  
Zhen Cai ◽  
Weiyan Zheng ◽  
Guoqing Wei ◽  
Xiujin Ye ◽  
Jingsong He ◽  
...  

Abstract Background: Bortezomib-dexamethasone-thalidomide has been reported to be effective in newly-diagnosed multiple myeloma (MM) with an overall response rate of 92% and a CR rate of 18% (Alexanian et al, Hematology12(3):235–239, 2007), but this regimen has not been reported in Chinese patients. We now report our experience with this combination. Objectives: To investigate the efficacy and safety of bortezomib in combination of dexamethasone plus subsequent thalidomide as primary treatment for MM. Patients and Method: Between June 2006 and August 2007, 11 consecutive newly-diagnosed patients with symptomatic MM were treated with bortezomib at 1.3 mg/m2 IV on days 1, 4, 8 and 11, dexamethasone at 20 mg/m2 IV daily on the day of bortezomib and the day after. All patients received daily oral thalidomide that was escalated from 100 mg to 200 mg. Seven of 11 patients were male and 4 were female. Median age was 57 years (range 47–86). Seven of 11 patients were stage 2 according to the International Staging System, 4 out of 11 patients were stage 3. Eleven patients received a median of 2 cycles of therapy (range 1–6). The Blade criteria were used for response evaluation. Toxicities were evaluated according to the NCI Common Toxicity Criteria version 3. Results: Nine out of 11 patients (82%) achieved PR and 2 (18%) achieved CR; therefore the overall response rate was 100%. With a median follow-up duration of 5 months (1– 14 months), no patients died. Grade 3–4 toxicities included fatigue (3/11), thrombocytopenia (3/11), diarrhea (3/11) and orthostatic hypotension (2/11). Grade 2 neuropathy occurred in 3 out of 11 patients, herpes zoster occurred in 3 out of 11 patients. Routine anticoagulation or anti-thrombosis was not used. There was no DVT/PE in 11 patients. Conclusion: Our preliminary experience indicated that bortezomib-dexamethasone-thalidomide is highly effective in newly-diagnosed MM. Grade 3 and 4 toxicities were rare after median 2 cycles of therapy. The relative lower rates of neuropathy and DVT/PE in this report with Chinese MM patients are being cautiously observed.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3082-3082
Author(s):  
Yi Li ◽  
Wenjun Wu ◽  
Jingsong He ◽  
Xiaoyan Han ◽  
Gaofeng Zheng ◽  
...  

Abstract Introduction multiple myeloma (MM) is currently an incurable hematological malignancy. Discovering molecular therapeutic targets is a new approach to improve the outcome in the treatment of the malignant disease. As CD200 is a type Ⅰmembrane glycoprotein expressed on myeloma cells, we asked if the expression of CD200 could serve as a prognostic marker for MM patients. Our data indicated that the expression level of CD200 is indeed correlated with the prognosis of the MM patients. Methods bone marrow samples from 96 newly diagnosed MM patients from April 2011 to July 2013 were evaluated by flow cytometry, using PE-conjugated anti-CD200 mAb, FITC-conjugated anti-CD138 mAb, and PE-Cy7-conjugated anti-CD45 mAb. PE-or FITC-conjugated normal mouse IgG was used as isotype-matched controls. Results 96 MM patients were investigated in the present study, including 60 men and 36 women, with a median age of 63 years (range 34–86 years). 81/96(84%) MM patients were CD200 positive with a median Mean Fluorescence Intensity (MFI) of 127 as analyzed by flow cytometry, which was consistent with the previous studies. While in 15 of 96 patients, CD200 expression was undetectable. Among the CD200 positive ones 7.40% patients were classified as stage Ⅰ, 12.35% were stage Ⅱ, and 80.25% were stage Ⅲ according to Durie–Salmon staging criteria. 40.74% patients were stageⅠ, 22.22% were stage Ⅱ, and 37.04% were stage Ⅲ, according to the International Staging System (ISS). Analysis of the CD200 positive patients revealed the MFI<127 group had a better progression free survival (PFS) (p=0.046) (Fig 1A) and overall survival (OS) (p=0.069) compared to those with MFI≥127. In the patients with age ≥65 years old, PFS (p=0.023) (Fig 1B) and OS (p=0.044) (Fig 1C) were much shorter in the MFI≥127 group, compared to the MFI<127 ones. Conclusions Our study demonstrated that the expression and MFI of CD200 on primary multiple myeloma cells is correlated with the prognosis of the MM patients. The better PFS and OS were observed in the MFI<127 group compared to the patients with MFI≥127, especially in the patients with age≥65 years old. Improved PFS in CD200 positive ones is likely due to the immune suppression mediated by CD200. Our study suggests that targeting therapy against CD200 may become a new approach to the treatment of MM in clinical practice. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5595-5595
Author(s):  
Naoki Takezako ◽  
Naoya Kaneko ◽  
Airi Hamano ◽  
Kenichi Ito ◽  
Naohiro Sekiguchi ◽  
...  

Background Although multiple myeloma remains an incurable disease, the triplet therapy with novel agents has significantly improved the prognosis. However, the utility of the novel agents is often not obtained in transplant-ineligible patients, particularly in unfit or frail patients because of the low tolerance. So, in real world, it is common to use a combination of lenalidomide and low dose dexamethasone (Rd), which are generally dose-adjusted. Certainly, in the elderly patients, triplet therapy including novel agents may be excessive treatment in terms of adverse events. However, patients with only partial response are known to have a poor prognosis, and it is important how to improve their prognosis. At our medical center, we select Rd therapy for elderly patients, except for fit patients, but we have switched to triplet therapy for patients who have not had a response above VGPR. Here, we retrospectively reviewed this treatment outcome. Method We retrospectively reviewed 71 transplant ineligible newly diagnosed multiple myeloma (NDMM) patients who received Rd therapy as initial therapy between November 2015 and March 2019. The median age was 73 years old (range 66~89). Patients received normal Rd therapy (lenalidomide 25 mg/day, day 1-21 (if they have normal renal function) and dexamethasone 20mg on days 1, 8, 15, 22) for every 4 weeks as initial therapy. If the response after 6 cycles was less than VGPR, another novel agent was added and treatment was continued as triplet therapy including lenalidomide. The International Staging System (ISS) were I in 15 (21.1%), II in 45 (63.3%) and III in 11 (15.5%). High-risk cytogenetics, defined as the presence of deletion 17, t(4;14) and t(14;16) by FISH analysis, were identified in 11 (15.4%) patients. The Revised International Staging System (R-ISS) were I in 14 (19.7%), II in 49 (69.0%) and III in 8 (11.2%). Results The overall response rate (ORR) after 6 cycles of Rd therapy was obtained in 69 (97.1%). including sCR in 5 (7.0%), CR in 3 (4.2%), VGPR in 23 (32.3%), and PR in 38 (53.5%). SD were observed in 2 patients (2.8%), respectively and they relapsed within six cycles. Twenty-nine out of 38 patients who had a response less than VGPR had changed to a triplet therapy with the addition of some novel agent (13 patients with elotuzumab, 5 patients with carfilzomib, 8 patients with ixazomib, and 3 patients with daratumumab). Forty-nine out of 71 cases (69.0%) achieved a response of at least VGPR, finally. The disease-free survival time was significantly longer in cases which obtained in excess of VGPR (figure). Grade 3 or greater toxicities occurring in 5% within 6 cycles, however, in triplet therapy, 6 patients (20.6%) were suffered from severe adverse events (most were infectious diseases such as pneumonia). Conclusion This retrospective analysis revealed that Rd therapy might be able to improve prognosis if patients obtain more than VGPR and even if treatment response is less than PR in the 6th cycle, triplet therapy might be effective to change the patients' prognosis. However, patients who do not reach VGPR even with triplet therapy have a poor prognosis and need further treatment. This results may be indicate that, in elderly NDMM patients, Rd therapy is sufficiently successful, and it is not always necessary to select triplet therapy as initial from the viewpoint of adverse events. Further study is warranted. Figure Disclosures Teshima: Novartis: Honoraria, Research Funding.


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