The detection of circulating plasma cells may improve the Revised International Staging System (R‐ISS) risk stratification of patients with newly diagnosed multiple myeloma

Author(s):  
Piero Galieni ◽  
Fosco Travaglini ◽  
Davide Vagnoni ◽  
Miriana Ruggieri ◽  
Patrizia Caraffa ◽  
...  
Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2115-2115
Author(s):  
Mark A Fiala ◽  
Michael Slade ◽  
Jesse Keller ◽  
Keith Stockerl-Goldstein ◽  
Michael Tomasson ◽  
...  

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.


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 ◽  
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 ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5756-5756
Author(s):  
Telma Nascimento ◽  
Adriana Roque ◽  
Emília Cortesão ◽  
Luís Francisco Araújo ◽  
Ana Isabel Espadana ◽  
...  

Abstract BACKGROUND: In the last decades, multiple myeloma (MM) prognosis has been changing dramatically. Induction with novel agents, followed by high-dose melphalan and autologous hematopoietic stem cell transplantation (aHSCT) is the standard of care for newly diagnosed (ND) and transplant-eligible MM patients (pts). In 2015, a new score was validated [Revised International Staging System (R-ISS)], including data related to high-risk cytogenetic abnormalities (CA) [del(17p) and/or t(4;14) and/or t(14;16)] and serum lactate dehydrogenase (LDH) levels. Few recent studies have supported R-ISS as a reliable prognostic tool for estimating survival in MM pts submitted to aHSCT. AIMS: To determine whether R-ISS is a valid risk model for predicting progression free survival (PFS) and overall survival (OS) among a cohort of real-life aHSCT pts. METHODS: We conducted a single center retrospective study of ND symptomatic MM pts treated with novel agents (bortezomib, thalidomide or lenalidomide) undergoing aHSCT between Jan/2007 and Dec/2017. We excluded all pts with no available information about ISS, LDH and CA [detected by fluorescence in situ hybridization (FISH)]. Response to treatment was evaluated according to the International Myeloma Working Group consensus criteria (2016). Statistical analysis was performed using STATA v.14.2 and significant levels were set at p<0.05. RESULTS: From the total number of 186 pts submitted to aHSCT, only 81 (45%) pts presented criteria to be included in our analysis; 62% were male, with a median age at aHSCT of 60y (28-70). IgG was the most frequent subtype (59%), followed by IgA (20%). At diagnosis, 38% of pts presented anemia, 14% renal impairment (RI), 20% hypercalcemia, 63% bone disease (BD) and 32% extramedullary disease (EMD). According to ISS, 30 (37%) pts presented stage I, 30 (37%) stage II, and 21 (26%) stage III at diagnosis. There were 38% pts with high-risk CA: 24% with del17p; 19% with t(4;14), and 20% with t(14;16). High LDH levels was seen in 48% of pts. Pts were re-staged at diagnosis according to R-ISS, resulting 17% in stage I, 61% in stage II, and 22% in stage III. Thus, 16 (20%) pts previously categorized as ISS I and 3 (4%) pts as ISS III were re-classified as R-ISS II. Median time from diagnosis to aHSCT was 9.7 months. All pts received induction therapy with novel agents (a bortezomib-based therapy in 89% of pts and an IMID-based in 12%), with 81% of pts responding to first line induction; 19% were refractory. At the time of aHSCT, all pts presented at least on partial response (PR) [62% at least very good partial response (VGPR)], with an increase in the proportion of pts in complete response (CR) from 15% to 20% before and after aHSCT, respectively. Maintenance therapy was performed in 31% of pts (79% thalidomide; 21% lenalidomide). At a median follow-up of 33.4 months, median OS had not been reached. Two-years OS was 62%. Median PFS from aHSCT was 67.4%.Neither high-risk CA nor high LDH levels individually predicted lower OS and PFS (p=NS). The 2-year OS for R-ISS I, II and III was 86 %, 61% and 44%, and the 2-year PFS was 79 %, 63% and 39%, respectively. In our cohort we observed statistical significance differences between R-ISS I and III at 2 years in what concerns PFS (p=0.025) and OS (p=0.017) . No differences were seen in between other R-ISS categories. When we stratified R-ISS stage II in two subgroups based on the presence or absence of high-risk CA no differences were found. Pts classified as R-ISS III presented anemia (p<0.001) and RI (p=0.001) more frequently, but no differences concerning hypercalcemia, BD or EMD. CONCLUSIONS: In our real-life cohort, R-ISS at diagnosis was a reliable tool only to predict both OS and PFS between R-ISS I and III and not between other R-ISS subgroups. The main reasons that explain the absence of significance between all R-ISS subgroups were probably the very low number of pts with available cytogenetics compared with the total number of pts submitted to aHSCT in our center and the short follow up of our study. Larger real-life studies with a longer follow up are necessary to determine if R-ISS is a good risk stratification model to applicate to NDMM pts submitted to aHSCT in the era of novel agents. 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.


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 (&gt;1 site) involvement (nine cases with EME). EMM patients had high levels of hemoglobin (Hgb, ≥10 g/dl) and serum lactate dehydrogenase (LDH, &gt;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.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5338-5338
Author(s):  
José Luís García de Veas Silva ◽  
Johanna Carolina Rojas Novoa ◽  
Carmen Bermudo Guitarte ◽  
Stephen Harding ◽  
Luisa Campos ◽  
...  

Abstract Background : The outcome for patients with Multiple Myeloma (MM) is highly variable. Understanding the prognosis for a particular patient can help when selecting the intensity of treatment to be used and the frequency of reviews. The International Staging System (ISS) is the current standard used for risk stratification of patients with MM. Recent studies have evaluated the relationship between serum free light chains (sFLC) at diagnosis and the prognosis of these patients. The aim of this study is to evaluate the prognostic value of sFLC ratio (sFLCR) at baseline in newly diagnosed MM in a Southern Spanish population. Materials and Methods : 180 patients (82 Male:98 Female) with a median age of 69 years (range 61-76) were recruited and followed for up to 7 years. The median follow up of the patients was 35 (18-61) months. sFLC concentrations were measured nephelometrically (Freelite, The Binding Site, Birmingham, UK) and the sFLCR was calculated using the monoclonal sFLC as the numerator. Patients were stratified into two groups according to the median value of sFLCR: group "low" with sFLCR<50 (90 patients) and group "high" with sFLCR≥50 (90 patients). Clinical and laboratory variables (including sFLC, Albumin, Beta-2-microglobulin (B2M), creatinine, hemoglobin, calcium, LDH, M-protein size, plasma cell infiltration and presence of lytic bone lesions) were recorded and evaluated for their impact on patient's outcome. Statistical analysis was performed using SPSS 23. Overall survival (OS) was analyzed by Kaplan-Meier method and significant variables were further analyzed by Cox Regression analysis. Results : During follow-up there were 72 disease-related deaths: 23 in group "low" and 49 in group "high". The 7-years OS of all patients was 38%, whereas it was 57% and 10% in groups "low" and "high" respectively (HR=5.07 IC95% 3.01-8.55, p<0.0001). Univariate analysis identified age>65 years old, creatinine>2 mg/dL, hemoglobin<10 g/dL, B2M>3.5 mg/L, albumin<3.5 g/dL, involved sFLC≥100 mg/L and ISS stages 2 & 3 as being significantly associated with adverse outcome (Table 1). There was no significant correlation with the others variables. Multivariate Cox regression identified sFLCR (HR=4.65, IC95% 2.71-7.98, p<0.0001) and B2M (HR=2.92, IC95% 1.67-5.11, p<0.0001) as independent risk factors for adverse outcome. The combination of sFLCR≥50 and B2M>3.5 mg/L allows us to include patients in a new model with three risk groups more accurate compared with ISS model (Table 2 and Figure 1). Conclusions : sFLCR value at diagnosis is an important independent risk factor for poor prognosis in patients with newly diagnosed MM. Our new staging system model based on sFLCR and B2M allow us an accurate risk stratification of patients with MM in our population. Table 1. Univariate and multivariate analysis of prognostic factors for patients with newly diagnosed MM. Variables Univariate analysis Multivariate analysis HR (95%IC) p-value HR (95%IC) p-value Age>65 years 1.99 (1.17-3.41) 0.01 - sFLC ratio≥50(involved/uninvolved) 5.07 (3.01-8.55) <0.0001 4.65 (2.71-7.98) <0.0001 Involved sFLC≥100 mg/L 2.19 (1.24-3.90) 0.007 - Total protein (g/dL) 1.45 (0.91-2.31) 0.2 - Calcium>11 mg/dL 1.75 (0.87-3.53) 0.2 - Hemoglobin<10 g/dL 1.95 (1.22-3.12) 0.005 - Creatinine>2 mg/dL 2.15 (1.25-3.70) 0.005 - Lytic bone lesions 1.21 (0.74-1.97) 0.4 - B2M>3.5 mg/L 3.66 (2.16-6.21) <0.0001 2.92 (1.67-5.11) <0.0001 Albumin<3.5 g/dL 1.84 (1.14-2.96) 0.01 - M-protein>3 g/dL 1.86 (1.07-3.21) 0.03 - Plasma cell>10% 1.57 (0.92-2.71) 0.1 - ISS-2 (vs. ISS-1) 3.02 (1.56-5.73) 0.001 - ISS-3 (vs. ISS-3) 4.88 (2.50-9,52) <0.0001 - Table 2. Prognostic value of International Staging System (ISS) and New Staging System based on sFLCR and B2M. NR=not reached. (1)p-value=0.09 between ISS-2 and ISS-3. (2)p-value<0.0001 between stages 2 and 3. Risk groups N Number of deceasesn (%) 7-years OS (%) Median survival(months) HR (95% CI) p-value International Staging System (ISS) Stage 1 56 14 (25) 56 NR 1.00 - Stage 2 65 30 (46) 33 51 3.02 (1.59-5.73) 0.001 Stage 3 59 28 (47) 0 44 4.88 (2.50-9.52 <0.0001 (1) New Staging System based on sFLCR and B2M Stage 1(B2M<3.5 mg/L and sFLCR<50) 53 12 (23) 63 NR 1.00 - Stage 2(B2M>3.5 mg/L or sFLCR≥50) 62 23 (37) 33 67 3.02 (1.49-6.13) 0.002 Stage 3(B2M>3.5 mg/L and sFLCR≥50) 65 37 (57) 0 35 11.60 (5.53-24.33) <0.0001 (2) Figure 1. Figure 1. Disclosures Harding: The Binding Site Group Ltd: Employment, Membership on an entity's Board of Directors or advisory committees. Campos:The Binding Site Spain: Employment.


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