Bortezomib-Based Chemotherapy Regimens Can Inmprove The Complete Remission In Newly Diagnosed Multiple Myeloma Patients With Bcl-2 and Survivin Overexpression

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5349-5349
Author(s):  
Zeng Wen ◽  
Huang Lifang ◽  
Yicheng Zhang ◽  
Sun Hanying ◽  
Liu Wenli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Complete Remission ◽  
Conflicts Of Interest ◽  
Clinical Manifestations ◽  
Staging System ◽  
Chemotherapeutic Agents ◽  
Tumor Burden ◽  
Newly Diagnosed ◽  
Double Positive ◽  
Research Fields

Abstract Compared with the traditional chemotherapeutic agents, Bortezomib-based chemotherapy regimens can increase the complete remission and improve the prognosis significantly in the newly diagnosed multiple myeloma patients. Molecular markers which can predict the chemotherapeutic efficacy and safety could help the physicians to make the right decisions and benefit the patients, and it has been one of most interesting research fields in MM. It has been reported that Survivin and Bcl-2 was involved in the adverse clinical events and therapeutic resistance, respectively. In order to investigate the relationship between the Survivin and Bcl-2 expression and the different regimens therapeutic efficacy, we retrospectively studied the proteins expression in the bone marrow biopsy specimens by inmmunohistochemistry and the efficacy of different chemotherapy regimens in the newly diagnosed MM in a single center of Tongji Hospital. Total 59 newly diagnosed MM were admitted into this study. The positive expression rate for Survivin and Bcl-2 was 35.3%（n=21）and 73.5%（n=43）, respectively. The protein expression had no relationship with the Durie-Salmon and International Staging System stratification, which suggested that Survivin and Bcl-2 were not responsible for the clinical manifestations. Bortezomib-based regimens (n=22) could effectively decrease the tumor burden and achieve response (CR+PR: 67.5% ). The non-bortezomib regimens (n=37), containing VAD(T), MP(T), TAD, were effective in the absent of Survivn and Bcl-2 expression(n=7; CR+PR 62.5% ). When Survivin and Bcl-2 were single or double positive (n=30), the newly diagnosed MM patients had no response for non-bortezomib regimens with none reaching complete remission or partial remission (p=0.0088). According to this study, we recommend the newly diagnosed MM which were Survivin and Bcl-2 single or double positive by inmmunohistochemistry received the regimens containing bortezomib for anti-myeloma therapy. Disclosures: No relevant conflicts of interest to declare.

The Expression Of CD200 As a Prognostic Factor In Newly Diagnosed Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3082-3082
Author(s):  
Yi Li ◽  
Wenjun Wu ◽  
Jingsong He ◽  
Xiaoyan Han ◽  
Gaofeng Zheng ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Flow Cytometry ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
Staging System ◽  
Newly Diagnosed ◽  
New Approach ◽  
Myeloma Cells ◽  
Targeting Therapy ◽  
Molecular Therapeutic

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.

scholarly journals 18F-FDG and 11C-Methionine PET/CT in Newly Diagnosed Multiple Myeloma Patients: Comparison of Volume-Based PET Biomarkers

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1042 ◽  
Author(s):  
Maria I Morales-Lozano ◽  
Oliver Viering ◽  
Samuel Samnick ◽  
Paula Rodriguez-Otero ◽  
Andreas K Buck ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Staging System ◽  
Tumor Burden ◽  
Newly Diagnosed ◽  
Focal Lesions ◽  
Pet Tracer ◽  
Standardized Uptake Values ◽  
Pet Ct ◽  
18F Fdg ◽  
Met Pet

11C-methionine (11C-MET) is a new positron emission tomography (PET) tracer for the assessment of disease activity in multiple myeloma (MM) patients, with preliminary data suggesting higher sensitivity and specificity than 18F-fluorodeoxyglucose (18F-FDG). However, the value of tumor burden biomarkers has yet to be investigated. Our goals were to corroborate the superiority of 11C-MET for MM staging and to compare its suitability for the assessment of metabolic tumor burden biomarkers in comparison to 18F-FDG. Twenty-two patients with newly diagnosed, treatment-naïve symptomatic MM who had undergone 11C-MET and 18F-FDG PET/CT were evaluated. Standardized uptake values (SUV) were determined and compared with total metabolic tumor volume (TMTV) for both tracers: total lesion glycolysis (TLG) and total lesion 11C-MET uptake (TLMU). PET-derived values were compared to Revised International Staging System (R-ISS), cytogenetic, and serologic MM markers such as M component, beta 2 microglobulin (B2M), serum free light chains (FLC), albumin, and lactate dehydrogenase (LDH). In 11 patients (50%), 11C-MET detected more focal lesions (FL) than FDG (p < 0.01). SUVmax, SUVmean, SUVpeak, TMTV, and TLMU were also significantly higher in 11C-MET than in 18F-FDG (p < 0.05, respectively). 11C-MET PET biomarkers had a better correlation with tumor burden (bone marrow plasma cell infiltration, M component; p < 0.05 versus p = n.s. respectively). This pilot study suggests that 11C-MET PET/CT is a more sensitive marker for the assessment of myeloma tumor burden than 18F-FDG. Its implications for prognosis evaluation need further investigation.

scholarly journals Comparative survival analysis using the International Stratification Score (ISS) in newly-diagnosed multiple myeloma in the Uruguayan population

2021 ◽  
Author(s):  
David Israel Garrido ◽  
Virginia Bove ◽  
Victoria Matosas ◽  
Eloisa Riva
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Latin America ◽  
Survival Analysis ◽  
Hematologic Malignancy ◽  
Staging System ◽  
Newly Diagnosed ◽  
Hematopoietic Stem ◽  
Survival Estimation ◽  
Real Practice

Background and aims. Multiple myeloma is a frequent hematologic malignancy, in which the International Stratification Score (ISS) is widely used to estimate the overall survival. However, there are no studies in Latin America evaluating its performance. This study aims to describe the ISS performance in the overall survival estimation for newly diagnosed multiple myeloma patients in Uruguay. Methods. This is a retrospective registry‐based survival analysis through the Grupo Uruguayo de Mieloma Múltiple (GUMMA) database, including newly diagnosed multiple myeloma patients from January 2001 until May 2019. Results. 249 patients were included, 51.81% males and an average age of 63.49 years. According to ISS and Durie-Salmon score (DSS), 47.79% and 82.3% were ISS III and DSS III, respectively. Also, 32.3% were DSS B. Auto hematopoietic stem cell transplantation was performed in 31.73% of patients, and bortezomib was used in 44.18% as frontline therapy. The overall survival was 80% for ISS1, 64.9% ISS2, and 48.6% ISS3 (Log-Rank; p <0.01). The average overall survival was 116.5 months for ISS 1, 77.6 months for ISS 2, and 57.8 months for ISS 3. The hazard ratio between ISS II and ISS I was 2.42 (95% CI 1.10-5.33; p<0.05), and 3.94 (95% CI 1.88-8.26; p<0.05) between ISS III and ISS II. Conclusion. The ISS staging system allows an adequate stratification of patients according to overall survival in the real-practice setting. However, considering the relevance of the new cytogenetic advances, it is necessary to increase the availability and quality of iFISH in Latin America.

scholarly journals Novel Insight into Multi-Hit Multiple Myeloma Based on "Two-Hit" Theory of Cancer Causation

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 47-48
Author(s):  
Chenxing Du ◽  
Xue-Han Mao ◽  
Jiahui Liu ◽  
Huishou Fan ◽  
Weiwei Sui ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Therapy ◽  
Conflicts Of Interest ◽  
Prognostic Significance ◽  
Staging System ◽  
Hazard Ratio ◽  
Drug Induction ◽  
Double Hit ◽  
Definition Of ◽  
Standard Risk

Background: Current definition of multi-hit multiple myeloma (MM) is based upon the number of high-risk cytogenetic abnormalities (CA). But we may overlook the influence of standard-risk CA and different concurrent patterns. In fact, standard-risk t(11;14) and del(13q) may bring extra danger when concurrent with other CA. And the concurrency of two secondary CA may do more harm to patients than that of one secondary CA with one primary CA. This study is to answer whether CA number or pattern exert an impact on outcomes of MM patients. Methods: This study was carried out based on the prospective, non-randomized clinical trial BDH 2008/02. 537 MM patients with complete cytogenetic data were enrolled, of whom 64% (341/537) patients were treated with bortezomib-based three-drug induction therapy, and the remaining patients with thalidomide-based therapy. Autologous stem cell transplantation (ASCT) was recommended post induction therapy in transplant-eligible patients, and all patients received maintenance therapy for two years. CA were divided into primary CA [pCA: any type of IgH breakage], and secondary CA [sCA: del(17p), del(13q), gain(1q) (≥3 copies)] Results: In the era of novel agents, patients with pCA only did not have outcomes different from those patients without any FISH abnormality. Patients with s1 CA or s1+p CA had hazard ratio for PFS or OS of 1.5-2.0. Patients with s2 CA or s2+p CA had hazard ratio for PFS or OS of 2.0-3.0. Patients with concurrent del(13q), del(17p) and gain(1q) (s3 CA) had hazard ratio for PFS of 3.11 and for OS of 3.00. Patients with s3+p CA had hazard ratio for PFS of 4.65 and for OS of 6.16. Based on these results, we divided patients into four subgroups: no CA or only pCA, s1 CA in the presence or absence of pCA, s2 CA in the presence or absence of pCA, and s3 CA in the presence or absence of pCA. Both the PFS and OS decreased in a stepwise fashion with the accumulation of CA (Figure 1). Therefore, we defined double-hit MM as any one sCA in the presence or absence of pCA. Triple-hit MM referred to two sCA plus pCA or not, and quadra-hit MM referred to three sCA plus pCA or not. Furthermore, we confirmed the prognostic independence of CA pattern in the multivariant analysis with International Staging System (ISS) and LDH (Table 1). Conclusion: In this study, we found that the primary CA as a whole lost its adverse effect when treated by bortezomib-based regimens. CA subtype conferred a prognostic value. In details, secondary CA imposed an accumulative risk to patients. For the first time, we indicated that double-hit or triple-hit MM should be defined upon the number of secondary CA. This definition coincides with the "Two-Hit" theory of cancer causation and fits well with MM evolution model. The prognostic significance of CA pattern needs validation in further prospective trials. Disclosures No relevant conflicts of interest to declare.

scholarly journals Efficacy of Modified Vrd-Lite for Transplant Ineligible Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 4-4
Author(s):  
Mizuki Ogura ◽  
Tadao Ishida ◽  
Moe Nomura ◽  
Hirofumi Irita ◽  
Junichiro Nashimoto ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Multiple Myeloma ◽  
Cardiac Amyloidosis ◽  
Staging System ◽  
Treatment Interruption ◽  
Cardiac Complications ◽  
High Dose ◽  
Al Amyloidosis ◽  
Newly Diagnosed ◽  
The Impact

BACKGROUND: High dose chemotherapy followed by autologous peripheral blood stem cell transplantation is an effective treatment for multiple myeloma. However, many patients with newly diagnosed multiple myeloma are transplant-ineligible because of their age and complications, result in a poorer prognosis than transplant-eligible patients. Furthermore, many of them cannot complete normal chemotherapy because of low tolerability. Here, we investigated the efficacy and safety of modified bortezomib with lenalidomide and dexamethasone (mVRD-lite) for transplant-ineligible patients with newly diagnosed multiple myeloma. STUDY DESIGN: A retrospective observational analysis was performed on patients who received mVRd-lite for the first line chemotherapy between Jan. 2016 and Mar. 2020 in our hospital. Patients who received high dose dexamethasone to reduce tumor burden, and patients who received bortezomib with dexamethasone or lenalidomide with dexamethasone as a reduction regimen of mVRd-lite were also included. We evaluated ORR, OS, PFS and adverse effect. mVRD-lite at first was administered over a 28-day cycle. Bortezomib 1.3 mg/m2 weekly was administered subcutaneously on days 1, 8, 15 and 22. Lenalidomide 15 mg was given orally 18 days, omitted on days 1, 8, 15, which are the days of bortezomib administration. Dexamethasone 20 mg was given orally on days 1, 2, 8, 9, 15, 16, 22, which are the day of and day after bortezomib. We also reviewed patients background, especially complication of light-chain amyloidosis and considered the impact of cardiac amyloidosis on patient prognosis. This study was conducted with the permission of the Ethics Review Board in our hospital. RESULTS: The subjects analyzed totaled 40 transplant-ineligible patients. 11(27.5%) patients were AL amyloidosis associated with multiple myeloma and 8(20%) patients had cardiac amyloidosis. Median age at diagnosis was 73 (range 48-86) and Male:Female=1:1. Most of them were judged inadequate to transplantation due to their age, general condition, or complication. One patient was ruled unfit to transplantation, because of his refusion. The Revised International Staging System (R-ISS) were I in 5 (12.5%), II in 25 (62.5%) and III in 8 (20%). 5(25%) patients switched to maintenance therapy. 17(42.5%) patients discontinued treatment, because of adverse effect (cardiac failure 4 ; two of them combined with cardiac amyloidosis, rash 4, peripheral neuropathy 3, infection 3, etc). 2(5%) patients died during treatment by mVRd-lite, because of Grade 4 adverse effect, such as pneumonia. 11(27.5%) patients died during observation period and causes of death were primary disease and TRM. 1(2.5%) patient was died of heart failure associated with cardiac amyloidosis. The overall response rate(ORR) during treatment period of mVRd-lite was obtained in 34(85%), including sCR in 5 (12.5%), VGPR in 13 (32.5%) and PR in 14(30%). 2(5%) patients achieved MRD negative. SD were observed in 3(7.5%) patients. 3(7.5%) patients were not evaluated efficacy because of treatment interruption by adverse effect. Overall survival rate at two year is 64.3%, median OS was not reached, at a median follow-up of 20 months. CONCLUSIONS: Transplant-ineligible multiple myeloma patients are associated with poor prognosis. Modified RVD-lite is one of the appropriate therapeutic options, in the transplant-ineligible multiple myeloma patients. Twenty-five percent of patients with cardiac amyloidosis had treatment discontinued due to cardiac complications. Further study is needed for treatment of patients with multiple myeloma complicated with cardiac amyloidosis. Disclosures Ishida: Janssen: Speakers Bureau; Celgene: Speakers Bureau; Ono pharmaceutical co: Speakers Bureau; Takeda pharmaceutical co: Speakers Bureau. Nashimoto:Janssen: Speakers Bureau; Celgene: Speakers Bureau. Tsukada:Takeda pharmaceutical co: Speakers Bureau. Suzuki:Takeda, Amgen, Janssen and Celgene: Consultancy; Takeda, Celgene, ONO, Amgen, Novartis, Sanofi, Bristol-Myers Squibb, AbbVie and Janssen: Honoraria; Bristol-Myers Squibb, Celgene and Amgen: Research Funding.

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.

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.

Metaphase Cytogenetics Adds to Gene Expression Profiling in the Identification of High Risk Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 114-114
Author(s):  
Guido Tricot ◽  
Fenghuang Zhan ◽  
Bart Barlogie ◽  
Yongsheng Huang ◽  
Jeffrey Sawyer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Prognostic Significance ◽  
Staging System ◽  
Treatment Modalities ◽  
Prognostic Impact ◽  
Newly Diagnosed ◽  
Prognostic Information

Abstract The International Staging System (ISS), based on B2-microglobulin and albumin levels at the time of diagnosis, has now generally been adopted as a new prognostic classification system for multiple myeloma (MM). While readily and widely applicable, ISS does not account for genetic disease features, such as metaphase (CA) and interphase fluorescence in situ hybridization (FISH) cytogenetic abnormalities, which when examined in the context of standard prognostic variables, confer higher hazards of relapse and disease-related death. Recently, gene expression profiling (GEP) uncovered the major prognostic significance for outcome of high expression of CKS1B, a gene mapping to an amplicon at chromosome 1q21. We have performed a comprehensive study of CA, FISH, GEP and ISS staging in 351 newly diagnosed MM patients, treated uniformly on Total Therapy 2. We have analyzed outcome based on a combination of high CKS1B by GEP and CA. GEP-based t(11;14) was prognostically favorable, irrespective of expression of CKS1B and, therefore, was removed from the group of patients with high CKS1B expression. After this adjustment, with the combination of both CA and high CKS1B (approximately 10% of all patients) conferred a very poor outcome with only 24% and 40% of such patients being event-free and/surviving at 3 years, compared with 72% and 84% for the others (p values : &lt;.0001). Such patients fared poorly, irrespective of their ISS stage. Similar prognostic information could be gained by combining CA with FISH-defined amplification of 1q21 and t(11;14). Because of their major prognostic impact, all newly diagnosed patients should be tested for these genetic markers. Novel treatment modalities are justified in the small subgroup of such poor prognosis patients, since they derive only a minor benefit from advances in MM therapy. CKS1B Q4 + CA (with no CCND1) vs. Others CKS1B Q4 + CA (with no CCND1) vs. Others

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