Durie-Salmon Stage Research Articles

P-195: Salvage autologous stem cells transplantation and maintenance therapy in relapsed refractory multiple myeloma

<h3>Background</h3> Multiple myeloma (MM) is an incurable hematological neoplasm. However, new therapies have improved overall survival (OS). In relapsed/refractory MM (RRMM) and a resource-limited environment, optimizing treatment options is essential. Autologous hematopoietic stem cell transplantation (ASCT) is an available strategy, frontline and at relapse <h3>Objective</h3> to analyze overall survival (OS2) and progression-free survival (PFS2) in RRMM patients comparing second-line consolidation strategies. <h3>Methods</h3> This retrospective survival analysis study, based on the Uruguayan Multiple Myeloma Registry, included all RRMM adult patients <66 years diagnosed in 2010-2020 who received second-line therapy. RRMM was defined according to international criteria. OS2 and PFS2 were measured from the identification of relapse until death/last control and progression, respectively. We used SPSSv.25 for statistical analysis. Survival was analyzed using Kaplan-Meier model with Log-Rank test, and Cox regression model along with hazard ratios (HR) <h3>Results</h3> Fifty-nine patients were included, with a median age at diagnosis of 56 years (IQR 12), 49.1% were male, 70.10% IgG, 84.75% were Durie-Salmon stage (DS) III and 37.3% ISS-III, 27.1% ISS-II, and 30.5% ISS-I. Age, ISS, and DS were not statistically different between therapeutic groups. Most (69.5%) patients had received a first ASCT, and 35.6% received maintenance as first-line therapy. Maintenance therapy was lenalidomide in 20.3%, thalidomide in 6.8%, and 8.5% other options. Eleven patients (18.6%) received salvage ASCT and maintenance, 18.6% received only ASCT, 16.9% received only maintenance and 45.8% neither ASCT nor maintenance. The median OS2 was 34 months, and PFS2 was 26 months. The 3-year OS2 and 3-year PFS2 were 47.2% and 32.2% for the entire cohort, respectively. The combination of ASCT and maintenance achieved a 3-year OS2 of 75.0% whereas OS2 in the non-combined therapy (NCT)(ASCT or maintenance) was 50.7% (HR 0.1, CI95% 0.01 to 0.6, p=0.01). ASCT and maintenance achieved a 3-year PFS2 of 43.1% whereas PFS2 was 37.6% for the NCT (HR 0.2, CI95% 0.1 to 0.7, p=0.01). The 3-year OS2 was 50.7% for those who received ASCT or maintenance vs. 28.4% for those without second-line consolidation (HR 0.3, CI95% 0.2 to 0.9, p=0.02). The 3-year PFS2 was 37.6% for patients who received any of the consolidative strategies vs 19.1% (HR 0.4, CI95% 0.2 to 0.9, p=0.02) in those who did not receive salvage ASCT or maintenance <h3>Conclusion</h3> ASCT has been recommended for patients relapsing after primary therapy, including an ASCT with an initial remission duration of >18 months. The role of salvage ASCT in patients who received lenalidomide maintenance has not been determined. In our analysis, the combination of ASCT and maintenance improved the OS2 and PFS2 compared to those treated with only ASCT or maintenance. Not receiving second-line consolidation was associated with inferior PFS2 and OS2.

P-124: The history of survival improvement in patients with Multiple Myeloma through real-world data in a 45-year period at a single institution

<h3>Background</h3> The prognostic landscape of multiple myeloma (MM) has evolved significantly over the last few decades. After the introduction of high-dose melphalan followed by autologous stem cell transplantation (HDM-ASCT) and, more recently, the first generation of proteasome inhibitors and immunomodulatory drugs have been implemented. There are, however, few data measuring such improvement in real-world patients. This study aimed to investigate trends in survival improvement over 45-years, and the associated clinical factors, in an unselected population of patients with MM in a single tertiary center. <h3>Methods</h3> Between 1970 and 2015, 1161 consecutive MM patients were included in the study. Patients were classified into three calendar periods (1970-84, 1985-99, and 2000-15), according to the treatment which they received; polychemotherapy, HDM-ASCT, and novel drugs, respectively. We analyzed relative (RS) to accurately evaluate MM-related death rates after excluding the mortality expected in the general population. In addition, we chose the Brenner's period method to estimate RS in patients diagnosed after 2000 in order to detect any recent advance towards statistical cure. <h3>Results</h3> After a median follow-up of 3.6 years (IQR: 1.4-6.5), 953 (82.1%) patients had died and 208 (19.9%) were censored alive. Median follow-up for survivors was 7.7 (IQR: 5.3-12.0) years. Median survival steadily improved from 1.7 years in 1970-1984 to 3.0 years in 1985-1999, and to 5.1 years in 2000-2015 (p<0.001). The estimated proportion of patients diagnosed before 2000 who survived more than 20 years was 6% (95% CI: 4.0-8.0). The 5-year RS improved from 27% in 1970-1984 to 38% in 1985-1999, and 56% in 2000-2015, and the 10-year RS improved from 10%, to 21%, to 33%, respectively. Patients younger than 65 years old, and those with ECOG performance status (PS) < 2, and Durie-Salmon stage I/II benefited the most from the improved survival, mainly in the 2000-2015 period. Nevertheless, even patients with ECOG PS ≥ 2 and Durie Salmon stage III improved their RS after 2000 in comparison with the two precedent calendar periods. At the multivariate Poisson regression analysis, increased age, poor ECOG PS, and advanced Durie-Salmon stage were independently associated with smaller improvements in RS. The estimated RS by Brenner's method in the patients diagnosed between 2000 and 2015 did not showed evidence of bending to the horizontal, which discarded statistical cure. <h3>Conclusions</h3> The survival rates of real-world patients with MM have improved over the last 50 years. The largest improvement was seen in younger patients and in those diagnosed after the year 2000, although older patients and those with more advanced disease or poor PS have also benefitted from increased survival. Unfortunately, there is no evidence for statistical cure and 5.1 years as median survival in the last time period still leaves significant room for improvement.

Outcomes of upfront autologous hematopoietic cell transplantation in patients with multiple myeloma who are 75 years old or older.

Consolidative autologous hematopoietic stem cell transplantation (AHCT) is commonly used for patients with multiple myeloma (MM). We studied AHCT use and outcomes in patients with MM ≥75 years old. Patients with MM ≥75 years old receiving AHCT between 2013 and 2017 in the United States were identified using the Center for International Blood and Marrow Transplant Research database. Relapse and/or progression (REL), progression-free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models. Covariates used were age, sex, Karnofsky performance score (KPS), HCT-comorbidity index (HCT-CI), International Staging System and/or Durie-Salmon stage, high-risk cytogenetics, melphalan dose, and disease status at and 1 year after transplant. AHCT utilization rate using the Surveillance, Epidemiology, and End Results database was used to estimate specific incidence among ≥75 years old by race and gender. Of 360 patients, 63% were male, 84% were White, 56% had KPS <90, and 57% had HCT-CI ≥3. The 100-day transplant-related mortality was 1% (0%-2%) with a 2-year REL rate of 27% (95% confidence interval [CI], 22%-33%), PFS of 66% (95% CI, 60%-72%), and OS of 83% (95% CI, 78%-87%). On multivariate analysis, only high-risk cytogenetics was associated with REL risk and decreased PFS. In White males, transplant utilization rate was 5.2%-5.8% compared to 3.5%-4.0% in African American males (P = .02). There was 3.37-3.79% transplant utilization in White females compared to 1.88-2.12% in African American females (P < .01). The use of AHCT was associated with excellent 2-year outcomes in this selected MM population ≥75 years old. Transplant utilization for patients ≥75 years old remains low with significant racial and gender disparities.

Prognostic nomogram incorporating cytokines for overall survival in patients with newly diagnosed multiple myeloma

ObjectiveThe purpose of this study was to explore the relationship between pretreatment cytokine status and overall survival and establish a prognostic nomogram incorporating cytokines in newly diagnosed multiple myeloma (NDMM) patients. MethodsA total of 121 patients with NDMM from the Wuhan Union Hospital were included in our study. Patient serum levels of cytokines, including macrophage inflammatory protein 1 alpha (MIP-1α), migration inhibitory factor (MIF), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor-α (VEGF-α), monocyte chemoattractant protein-1 (MCP-1) and soluble interleukins IL-17A, IL-6, IL-21 and IL-10 were assessed before treatment. Based on the results of the multivariate Cox proportional hazards model, we developed a prognostic nomogram. We used the concordance index (C-index) and a calibration curve to measure the predictive performance of the nomogram. ResultsThree important variables (lactate dehydrogenase, MIP-1α and creatinine) were incorporated in the nomogram using multivariate Cox analysis. The 3-year overall survival (OS) rate and progression-free survival (PFS) rate were 83.8% and 21.8% in the low-risk group of the nomogram and 17.4% and 8.4% in the high-risk group, respectively. The C-index of the nomogram for OS prediction was 0.80 (95% CI: 0.68–0.92), showing superiority over the predictive power of the Durie-Salmon staging system (C-index = 0.58; 95% CI: 0.49–0.67), International Staging System (C-index = 0.70; 95% CI: 0.61–0.79) and Revised-International Staging System (C-index = 0.71; 95% CI: 0.63–0.80). The calibration curve showed that the nomogram accurately predicted the 1-year, 2-year and 3-year OS of NDMM patients. ConclusionThe established nomogram provides accurate and individualized OS risk estimation for NDMM patients.

Utility and Clinical Implications of Appendicular Skeleton Magnetic Resonance Imaging in Multiple Myeloma: A Single-Institutional 15-Year Experience.

The aim of this study was to evaluate the utility of appendicular skeleton magnetic resonance imaging (MRI) in the management of multiple myeloma over 15 years. A total of 107 appendicular MRIs were obtained from 67 patients. Variables including age, sex, diagnosis, stage, indication, transplant status, MRI result, and treatment course were analyzed. The most common indication was pain (76.6%). The most commonly affected bone groups were the proximal lower (54.3%) and upper extremity (47.6%). Most (83%) positive examinations demonstrated focal disease. Advanced Durie-Salmon stage was associated with increase in appendicular disease (P = 0.0056). Increasing age and prior negative positron emission tomography/computed tomography were associated with a decrease in appendicular disease (P = 0.0036 and 0.0011). When neoplasm was seen, 58.5% underwent management alteration. Advanced stage and history of relapse were associated with treatment alterations (P = 0.0096 and 0.0031). Appendicular MRIs comprised 9.6% of MRIs ordered. Appendicular MRI elucidates both neoplastic and nonneoplastic causes of pain. Most examinations with MRI positive for myeloma had subsequent skeletal disease and resulted in altered management.

Epidemiology and Analysis of Early Mortality of Patients with Multiple Myeloma in Russia According to the Kirov Regional Population-Based Database

Multiple myeloma (MM) is a heterogeneous disease with the survival ranges from a few months to 10 years and more. The prevalence of MM varies according to ethnicity and geographical backgrounds. The real incidence of this disease in Russia is poorly understood. Available data are limited. Although the survival of MM patients has increased over the past 10-15 years, there is still a proportion of patients who die within a few months during induction therapy. The aim of this study was to examine the incidence of MM in Russia, describe characteristics of newly diagnosed MM patients, and assess patient survival, using the data from a population-based primary care database. Moreover we identified the clinical and laboratory features that are associated with early death within the first 12 months after initiation of antimyeloma therapy.Methods. Patients with new diagnosed MM were identified in the Kirov regional population-based primary care database (dates of diagnosis ranged from 01 Jan 1994 to 31 Dec 2016). Demographic and clinical characteristics were described at time of diagnosis. Median overall survival (OS) was estimated using Kaplan-Meier methods using individual patient level data from diagnosis date to date of death or end of follow-up. Survival rates were stratified by 5-year periods by calendar year of diagnosis: 1994-1999, 2000-2005, 2006-2011 and 2012-Dec 2016.Results. The five hundred and sixty seven patients with new diagnosed MM (male - 215, female - 352) were included in this study. Median age of the patients was 64 years (range, 29-90 years). The age-standardized incidence of MM was 1.8 cases per 100.000/year. During research period (23 years) we have the positive trend of the incidence and prevalence of MM and negative tendency of mortality every year. Our prognosis of the intensive incidence is 2.2-2.3 cases per 100.000 in 2017-2019 years. The 5-year OS rate was 18% (1994-1999); 24% (2000-2005) and 36% (2006-2011) respectively (Fig. 1). The median OS was 28; 26 and 38 months respectively. The median OS for patients who diagnosed in the period 2012-2016 was not achieved.The incidence of early mortality was different in selected observation periods. In particular it was 45% between 1994 and 1999, 43% in 2000-2005, 36% in 2006-2011 and 11% between 2012 and 2016. These frequencies differed from each other (X-squared = 22.125, df = 3, p-value = 6.143e-05). The impact of age, hemoglobin and platelets levels, serum creatinine, LDH, albumin, B2-microglobulin, plasma cells in bone marrow, immature plasma cells in bone marrow, Durie-Salmon stage, IgA type and treatment by proteasome inhibitors (bortezomib) were estimated as predictors of a short survival rate. Based on the results of univariate analysis age, Durie-Salmon stage III, bortezomib treatment, hemoglobin level, B2-microglobulinum, serum creatinine and albumin were found to be significant (p<0.05). These factors were evaluated in multivariate analysis. In multivariate analysis the strongest predictors of death within <12 months were hemoglobin level (HR: 0.97, 95% CI: 0.94-0.99, p=0.04), B2-microglobulin (HR: 1.09, 95% CI: 1.03-1.15, p=0.002) and using bortezomib in treatment (HR: 0.17, 95% CI: 0.05-0.45, p=0.0007). According analysis the using bortezomib in treatment of MM patients reduce risk of early mortality in 5.9 times. The odds ratio for dying in the first year was 0.13 (CI: 0.07-0.25) for patients receiving a bortezomib compared to the rest.Conclusion. The age-standardized incidence of MM in Kirov region (Russia) was 1.8 cases per 100.000/year. 5y-OS was 18% (1994-1999); 24% (2000-2005) and 36% (2006-2011). In newly diagnosed MM low hemoglobin level and high B2-microglobulin levels were associated with high risk of early mortality (<12 months after initiation of antimyeloma therapy). In 2006-2016 recent years a novel agents (bortezomib, lenalidomide) for treating MM have been introduced, which according to our database is associated good outcome and low risk of early mortality. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Gene Expression Profiling (GEP) As a Prognostic Indicator of Multiple Myeloma, Irrespective of Disease Stage, Prior Treatment and Prior Transplant - a Single Center Experience

BackgroundMultiple myeloma (MM) risk is classified using fluorescence in situ hybridization (FISH) routine cytogenetics, and gene expression profiling (GEP). GEP is a clinically validated tool for prognostication of MM in newly diagnosed and relapsed patients (pts), its role in very heavily treated stages is less clear. A study (Nishihori et al, ASH, 2016) concluded that GEP is useful regardless of disease stage. We aim to determine the prognostic significance of GEP heavily pre-treated MM cohort.Methods299 pts with MyPRSTM GEP results at Hackensack University Medical Center (NJ) between 2012 and 2016 were included. High risk GEP was defined with the validated cutoff score of >45.2, high risk FISH was determined according to the mSMART classification as del17p, t(14,16), t(14,20). Chi-square tests were performed on categorical data and Wilcoxon rank sum tests on continuous data. Overall survival (OS) and progression free survival (PFS) were performed using Kaplan-Meier.ResultsMedian age was 63 years (range, 25-91), 170 pts (56%) were men, 81 pts (28%) had International Staging System (ISS) 3 and 191 pts (62%) had Durie-Salmon Staging (DSS) III. 245 pts (81%) had at least one bone marrow transplant (BMT). Median time from myeloma diagnosis to GEP was 30.1 (range 0.1-178.4) months. Most pts had GEP on diagnosis but 24% were heavily pretreated (range, 1-6 lines of treatment), and 13% had a BMT prior to GEP testing. 77 pts (25%) had high-risk disease based on GEP with a median score of 36.5 (range, 9.03-84.05). Molecular subtypes were hyperdiploidy (HY) 31%, cyclin family (CD)-2 20%, low bone disease (LB) 13%, proliferation (PR) 11%, MAF associated (MF) 10%, CD-1 8%, and MMSET associated (MS) 6%. Median OS and PFS were significantly inferior in patients with high-risk by GEP, 25 vs 33 months (p<0.021), 13 vs 21 months (p<0.004) respectively. Molecular subtypes were not individual predictors of OS (p<0.2). When MF, MS and PR subtypes were combined, they had inferior OS compared to other subtypes but this was not statistically significant (p<0.3).ConclusionsGEP can accurately predict risk status in heavily pre-treated and post-transplant MM pts. In conclusion, our data confirm that GEP is a good prognostic indicator in MM pts irrespective of disease stage and prior treatments. Further prospective studies with larger samples and correlating with baseline and intra-treatment GEP are needed. DisclosuresRichter:Janssen: Speakers Bureau; BMS: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Vesole:Takeda: Speakers Bureau; Celgene: Speakers Bureau. Siegel:Celgene, Takeda, Amgen Inc, Novartis and BMS: Consultancy, Speakers Bureau; Merck: Consultancy. Biran:Takeda: Speakers Bureau; Celgene, Amgen: Consultancy, Speakers Bureau.

Randomized Phase III Study (ADMYRE) of Plitidepsin in Combination with Dexamethasone Vs. Dexamethasone Alone in Patients with Relapsed/Refractory Multiple Myeloma

Randomized Phase III Study (ADMYRE) of Plitidepsin in Combination with Dexamethasone Vs. Dexamethasone Alone in Patients with Relapsed/Refractory Multiple Myeloma

Prognostic Relevance of Clonal Circulating Plasma Cells Detected By Multiparameter Flow Cytometry in Patients with Newly Diagnosed Multiple Myeloma Treated with Novel Agents: Comparative Investigation with the Revised International Staging System

BackgroundAlthough previous studies demonstrated the presence and prognostic significance of clonal circulating plasma cells (cPCs) detected by multiparameter flow cytometry (MFC) in patients with multiple myeloma (MM), monocle gammopathy of undetermined significance (MGUS), and smoldering MM (sMM), most were conducted during the pre-novel agent era. The relationship between cPC quantification and the revised international staging system (R-ISS) has not been elucidated thus far. We retrospectively analyzed the prognostic significance of cPCs in patients with newly diagnosed MM (NDMM) receiving novel agent-containing induction therapies and their relationship with R-ISS.Patients and methodsFrom November 2007 to April 2017, we evaluated clonal cPCs of newly diagnosed, symptomatic MM patients admitted to Kameda Medical Center, Kamogowa-shi, Japan. We retrospectively analyzed clonal cPCs at diagnosis. Diagnosis and assessment of response to treatment were made according to IMWG criteria. Survival analysis was performed using Kaplan-Meier curve and differences were assessed by log-rank test. Two-tube 6- or 7-color MFC was performed on peripheral blood mononuclear cells (MNCs), isolated by the Ficoll-Hypaque density gradient]. We stained MNCs with monoclonal antibodies to CD45, CD38, CD19, CD138, CD56, and cytoplasmic kappa and lambda light chains. To achieve a sensitivity of 0.01%, we required 500,000 events. Negative cPC was defined as <1 clonal cPC detected by MFC among 10,000 events. Clonal cPCs were expressed as the number per 500,000 total events. Receiver operating characteristics (ROC) analysis determined the optimal cutoff levels of cPCs for predicting the highest risk of disease progression within 3 years for all patients and patients with R-ISS stage Ⅱ, and disease progression within 2 years for patients with R-ISS stage Ⅲ.ResultsClonal cPCs were measured in 132 patients and detected in 95 patients (72.0%). The median number of clonal cPCs was 228 [interquartile range (IQR), 28-1,362] per 500,000 total MNCs. ROC analysis showed the optimal cutoff for predicting the highest risk for disease progression within 3 years, in all cohorts, to be 500 cPCs per 500,000 MNCs, yielding an area under the curve (AUC) of 0.649 with a sensitivity of 65.0% and a specificity of 64.1%. All 132 patients were divided into patients with higher (≥500) and lower (<500) cPCs. Comparing the higher and lower clonal cPCs groups, male sex, patients with advanced clinical stage (ISS, R-ISS, and Durie-Salmon stage), albumin, β2-microglobulin, hemoglobin, lactate dehydrogenase, and presence of high-risk cytogenetic abnormality (CA) were significantly associated with the higher clonal cPC group. Survival analysis showed that patients in the higher clonal cPC group had significantly shorter progression-free survival (PFS) [median survival; 52.2 vs 21.9 months (m), P=0.001] and overall survival (OS; median survival; not reached vs 40.7 m, P=0.02). These survival differences remained significant when separately analyzed in patients with R-ISS stage II and stage III (median PFS, 17.9 vs. 41.2 m; P=0.002, and median OS, 40.4 m vs. not reached; P=0.040, in patients with R-ISS stage II, and median PFS, 6.6 vs. 44.9 m; P=0.004, and median OS, 35.8 m vs. not reached; P=0.025, in patients with R-ISS stage III). We used univariate analysis to assess clinical variables and determine their survival effects. High-risk CA, ISS ≥stage II, and higher cPCs were significantly associated with a shorter PFS and ISS. For patients with R-ISS ≥stage II, higher cPCs were associated with OS. Multivariate analysis showed higher cPCs to be independent predictors of poor PFS after adjusting for high-risk CA, ISS ≥stage II, R-ISS ≥stage II and maintenance therapy (P=0.001).cPCs also independently predicted poor OS after adjusting for age, ISS ≥stage II, and R-ISS ≥stage II (P=0.017).ConclusionQuantification of cPCs by MFC predicts PFS and OS in patients with NDMM, treated with novel agents. It also showed prognostic significance in patients with the same R-ISS categories (both stage Ⅱ and Ⅲ,), suggesting that it is an independent prognostic predictor of R-ISS and has potential for refining the current prognostic system, including R-ISS. [Display omitted] DisclosuresKitadate:Toyama kagaku: Research Funding; Otsuka: Research Funding; Eisai: Research Funding; Kyowa Kirin: Research Funding; Fujimoto: Research Funding; Pfizer: Research Funding; Novartis: Research Funding; Asahi Kasei: Research Funding; Chugai: Research Funding.

Conditioning Chemotherapy with BOR-MEL in Autologous Stem Cell Transplant in Multiple Myeloma

INTRODUCTIONIn multiple myeloma (MM) the intensive chemotherapy strategy followed by autologous stem cell transplantation (ASCT) has improved the overall median survival of patients with MM from 36 months to more than 5 years in patients at standard risk. Despite modern therapy, most patients with MM will have disease progression. Several prognostic factors have been identified for the progression of the disease, such as beta-2-microglobulin, albumin (international staging system score), elevated serum lactate dehydrogenase and certain chromosomal abnormalities such as t (14; 16), 17 , 8q21 and the loss of 1p or gains of 1q. Among the main strategies to achieve the best response in the transplanted MM, is the improvement of the conditioning regimen.In some Latin American cities, access to melphalan IV is limited, the use of oral melphalan has been previously reported. The addition of bortezomib to high doses of melphalan has been reported by several groups and has shown that the toxicity profile Is comparable to the high doses of Melphalan (mel200).OBJECTIVESTo assess the impact of bortezomib in combination with oral doses of oral melphalan (BorMel) on progression-free survival and overall survival of patients with multiple myeloma. We will also assess the toxicity and complications that occur during and after transplantation as well as time of grafting of both neutrophils and platelets.METHODS AND PATIENTSIt is a unilateral, observational, descriptive study that included patients 18 to 70 years of age with diagnosis of multiple myeloma included in the program of autologous stem cell transplantation at the National Medical Center “20 de Noviembre” in the Hematology Service since 2010 to 2017. All of them received oral melphalan 200mg / m2SC conditioning from day -5 to -2, in addition to Bortezomib 1.3mg / m2SC on days -11, -8, -4, -1.RESULTSWe included 47 patients, of whom 31 (65.9%) were men and 16 (34.1%) were women. The median age was 52 years (31-67 years).Regarding the immunoglobulin involved, 55% were IgG (26 patients), 12% IgA, non-secretors 8%. The Durie-Salmon stage I, II and III were 15, 14 and 71% respectively, 100% received first line bortezomib, the combination with Cyclophosphamide in 25%, Thalidomide 36% and Doxorubicin 29% mainly. To be admitted to ASCT, they had to have at least MBRP, 73% of the patients were transplanted after the first line of treatment, 17% required a second line, of these 4 (8.5%) by primary progression. The mobilization was based on Cyclophosphamide in 76.6%, the median of mononuclear cells obtained was 3.19 x 10(8) CMN / kg. There was no difference in the myeloid and platelet graft with mean of 13 days with a range of 9 to 24 days . During transplantation, 10% of the patients presented gastrointestinal toxicity, an infectious process in 40%, and the upper airway infection in 8%, the mortality during transplantation was 0%. 94% of patients entered maintenance treatment. At present, 63% of the patients continue to be maintained, progression-associated death in 6%, 17% in follow-up in other units, 25% progressed with an average of 18 months posttransplant.CONCLUSIONSThe addition of bortezomib to oral melphalan proved to be safe, as it did not increase toxicity or transplant-related mortality, however, if there was an improvement in event- free survival when compared with previous studies of oral melphalan, where the mean was 14 months. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The Impact of M-Protein Screening-Driven Early Diagnosis on Mortality from Multiple Myeloma in China

Introduction:The annual incidence of MM in China is 0.6/100,000, much lower than that in United States (6.6/100,000). Despite ethnic disparities and hereditary distinction, the difference in incidence between China and US may also be attributed to unscientific health-seeking behavior that Chinese people are less likely to receive routine body examination and often delay seeking health service. Furthermore, primary care physicians in China often lack awareness of early signs of myeloma. Therefore, most myeloma patients in China were diagnosed and treated only until severe complications occurred, with 85.8% of patients staged as Durie-Salmon stage III at diagnosis. Meanwhile, Chinese myeloma patients suffer from an inferior outcome, with a median overall-survival of only 4.5 year.In Zhongshan Hospital, Fudan University, a large national reference center in Shanghai delivering medical service for over 3,400,000 patients annually, serum protein electrophoresis (SPEP) is routinely incorporated into liver biochemical and function tests, and therefore providing us unique opportunities to observe the prevalence of monoclonal gammopathy in a hospital population, to screen and identify patients with myeloma or other monoclonal immunoglobulins (M-protein) related disorders at earlier stage, and to evaluate the impact of M-protein screening on baseline characteristics and outcome of patients with MM.Methods:Given every patient receiving liver biochemical tests were routinely screened for M-protein by SPEP in our institute, we initiated a standardized M-protein screening procedure based on SPEP screening in hospital population (Figure Panel A),In this retrospective cohort study, we examined records of hospitalized newly diagnosed MM patients with complete data from January 2013 to December 2016. MM patients with concurrent cardiac amyloidosis were excluded due to distinct prognosis. Patients were categorized by the means of detection of the disease. Patients were considered in screening-driven group if they had an incidental finding of M-protein during workup of unrelated medical conditions and had a visit with hematologist in M-protein specialized clinic or during consultation. Symptom-driven group included patients visited or were referred to hematologic department due to suspected myeloma-related end-organ damage. Baseline characteristics, treatment, overall survival (OS) and progression-free survival (PFS) were compared. Institutional ethics committee approved the study and informed consent was waived.All tests were 2-sided (SPSS version 21.0 was used) and a P -value < 0.05 was considered statistically significant.Results:We identified 193 eligible MM patients. The Table summarizes the baseline features. Compared to symptom-driven group, patients in screening-driven group had earlier DS stage disease (DS III 74.3% vs 89.9%, P= .004), lower frequency of anemia (66.2% vs 81.5, P= .016) and bone lesion (73.0%vs 90.8%, P= .001), and lesser number CRAB symptoms (P= .000).The Figure (panel B and C) depicts survival of MM patients. Patients diagnosed via M-protein screening demonstrated significantly (HR 0.358, 95% CI, 0.138-0.932; P= .035) better outcome (2-yr OS, 89.9%; 95% CI, 75.9%-95.9%) than those in symptom-driven subgroup (2-yr OS, 73.1%; 95% CI, 62.2%-81.3%; HR 1) after adjusted for age, gender, treatment and number of CRAB symptoms with a Cox proportional hazards model.Discussion:Although M-protein screening in normal population is not currently recommended, the impact of myeloma screening in hospital population has not been studied. This very first report reveals increased detection of early stage myeloma and remarkable survival improvement resulted by M-protein screening in hospital population in China. Early detection and prolonged survival implies improvement in health-related Quality of Life and more opportunities to receive further lines of treatment when disease relapses, which is critical for Chinese MM patients, given that most of them were diagnosed and treated only after severe complications developed. Moreover, our data suggests that shortening the time between initial occurrence of end-organ damage and myeloma-targeted treatment by early detection may lead to better outcome.Limitations of this report include its retrospective observational design, relying on data from a single center, and relatively insufficient follow-up. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Bortezomib Consolidation after Nonmyeloablative Allogeneic Transplant Is Safe and Leads to a High Incidence of Immunophenotypic Complete Response in High-Risk or Young Myeloma Patients

▪Introduction: Allogeneic stem cell transplantation (alloSCT) is the only curative treatment for newly diagnosed multiple myeloma (NDMM) patients but is hampered by a high incidence of relapse and chronic graft-versus-host disease (cGVHD). We hypothesized that bortezomib (BTZ) in consolidation after tandem autologous stem cell transplantation (ASCT) and nonmyeloablative (NMA) alloSCT could decrease the incidence of cGVHD while improving quality of response.Method: NDMM patients ≤65 years with high-risk (HR) disease (defined as HR cytogenetics [del17p, t(4;14), t(14;16), t(14;20), del1p or gain 1q], ISS 3 or plasma cell leukemia) or ≤ 50 year regardless of risk status with an 8/8 HLA identical sibling or unrelated donor are eligible to participate in this prospective trial. After triplet BTZ-based induction chemotherapy and ASCT, outpatient NMA alloSCT is performed with either fludarabine 30 mg/m2 and cyclophosphamide 300 mg/m2 for 5 days (sibling donor) or fludarabine 30 mg/m2 for 3 days and total body irradiation 2 Gy (unrelated donor) followed by peripheral blood stem cell infusion. Acute GVHD (aGVHD) prophylaxis consists of tacrolimus and mycophenolate mofetil (MMF). BTZ is started on day +120 post-transplant at 1.3 mg/m2 every 2 weeks for 1 year. Response evaluation is based on IMWG criteria. Bone marrow minimal residual disease (MRD) evaluation is performed with highly sensitive (≥10-5) next-generation flow cytometry using 8-color Euroflow protocol before alloSCT, before BTZ, every 3 months for 2 years and at relapse. Immunophenotypic complete response (iCR) is defined as stringent CR in addition to 2 consecutive negative MRD results. aGVHD and cGVHD are evaluated according to modified Glucksberg and NIH criteria, respectively.Results: As of 07/10/2017, 33 NDMM patients (16 males) have been enrolled; median age is 55 (range: 35-64) years. ISS 3 is found in 39%, Durie-Salmon stage 3A or 3B in 85%, HR cytogenetics in 58% (12% del17p, 15% t(4;14), 33% gain 1q21, 9% del1p and 12% with >1 HR cytogenetics). Induction consisted of CyBorD (79%) or VTD (21%) for a median of 4 (range: 4-7) cycles followed by ASCT. Median times from induction to ASCT and from ASCT to alloSCT are 5.7 and 4.4 months, respectively. Sibling donor transplants were performed in 42%. With a median follow-up of 15 months after alloSCT, 23 patients have started BTZ and received 96% of planned doses. No dose reduction was needed for toxicity. Consolidation BTZ improve depth of response, increasing ≥CR rate from 55% to 80% and iCR rate from 17% to 67% (Table 1), regardless of cytogenetic abnormalities. Median progression-free survival (PFS) is not reached; 12-month PFS is 87% (CI: 66-96) (Fig. 1). The cumulative incidence of progression at 12 months is 8%. Median overall survival (OS) is also not reached and 12-month OS is 91% (CI: 68-98). In 23 patients followed ≥6 months, cumulative incidences of grade II-IV and grade III-IV aGVHD are 30% and 15%, respectively. In 18 patients followed ≥12 months, the cumulative incidence of all grade and moderate-severe cGVHD at 12 months are 58% and 40%, respectively, with mostly mouth, skin and liver involvement. There is no clear association between time of occurrence of cGVHD and improvement of response. Three patients died, one from myeloma progression and 2 from grade III aGVHD, with a non-relapse mortality at 12 months of only 5%. Observed grade ≥3 non-hematologic toxicities possibly/related to BTZ include diarrhea (n=1), viral hemorrhagic cystitis (2 adenovirus, 1BK virus) and subclinical EBV reactivations (n=4).Conclusion: Tandem ASCT-NMA alloSCT and BTZ consolidation result in a remarkably high rate of CR or better including iCR. Despite a HR NDMM population, a low relapse rate is observed. BTZ following alloSCT is safe and may contribute to decrease both the incidence of cGVHD or its severity. [Display omitted] DisclosuresSebag:Celgene, Janssen: Consultancy. Cohen:University of Montreal: Patents & Royalties: royalties.

A Comparison between 3 Staging Systems in Multiple Myeloma Using the Center for International Blood and Marrow Transplant Research (CIBMTR) Database

Background: The International Staging System (ISS) which has 2 components, serum albumin and beta-2 microglobulin, has been used effectively to prognosticate newly diagnosed multiple myeloma (MM) since 2006 when it effectively replaced the Durie-Salmon staging system. In 2014, the International Myeloma Working Group proposed a system inclusive of ISS incorporating molecular markers and age (IMWG-2014). More recently, the revised- ISS (R-ISS) including ISS, high risk molecular markers and serum LDH at diagnosis has been proposed and validated in Europe. We hypothesized that the IMWG-2014 and R-ISS are more prognostic of outcomes than the ISS.Methods: MM patients identified in the CIBMTR database who underwent first AHCT in 2008-2014 with high dose melphalan after novel therapy induction, within 18 months of diagnosis, and with available diagnostic LDH and molecular studies were included (n= 628). Patients were categorized into each of the 3 systems: ISS, IMWG-2014 and R-ISS. The relative risk of relapse/progression, progression-free survival and overall survival was calculated using the Cox proportional hazards regression with staging system as predictor. We computed a measure of separation (SEP) for the Kaplan-Meier curves, with larger numbers representing more separation. Agreement between the systems was determined using the kappa statistic.Results: The number of patients in each group were as follows: ISS I, N=244; ISS II, N=214) and ISS III, N=170, IMWG-14 low, N =130; standard N=451 and high N=47, and R-ISS stage I, N=199; R-ISS II, N=360 and R-ISS III, N=69. Table 1 shows the baseline characteristics of the cohort. Multivariate analysis comparing outcomes in this cohort using 3 prognostic models found statistically significant hazard ratios for PFS and OS when comparing stages in all models except for PFS when using the IMWG-2014 model (PFS 0.06) (Table 2). The SEP was 1.74 using the R-ISS, 1.60 using the IMWG-2014 and 1.58 using ISS for OS. For PFS, the SEP was 1.59 using R-ISS; 1.24 using the IMWG-2014 and 1.42 using ISS (Table 2). Greater separation was seen in the R-ISS survival compared to ISS and IMWG- 2014, which was also reflected in the higher hazard ratios. Figure 1 shows OS by ISS (1A), R-ISS (1B) and IMWG-2014 (1C). Upon measuring agreement between ISS and R-ISS, the weighted kappa statistic was 0.78 (95% CI 0.74-0.81) denoting good agreement between the 2 systems, but only 0.30 (95% CI 0.25-0.35) between ISS and IMWG-2014.Conclusions: Although all 3 models are valuable, the R-ISS system provides the greatest degrees of separation between survival curves and thus most accurately delineates the differences between the 3 stages, followed by the ISS. R-ISS has good agreement with ISS. [Display omitted] DisclosuresHari:Celgene: Consultancy, Honoraria, Research Funding. Kumar:Celgene, Millennium/Takeda, Onyx, AbbVie, Janssen, Sanofi, Novartis, Amgen, Genentech, Merck, Oncopeptides, Roche, Skyline Diagnostics: Research Funding; Celgene, Millennium, BMS, Onyx, Janssen, Noxxon, AbbVie, Amgen, Merck, Oncopeptides, Skyline Diagnostics, Takeda: Consultancy; Skyline: Honoraria. Gasparetto:Janssen, BMS, Celgene: Consultancy; Celgene: Research Funding; Janssen, BMS, Celgene, Takeda: Honoraria; Janssen, BMS, Celgene: Other: Travel, accommodations, or other expenses paid or reimbursed. D'Souza:Celgene: Consultancy; Prothena: Research Funding; Merck: Research Funding.

The Prognostic and Predictive Value of IKZF1 and IKZF3 Expression in T-Cells in Patients with Multiple Myeloma

PURPOSE:The report of cereblon being the target for immunomodulatory drugs, and the subsequent degradation of Ikaros (IKZF1) and Aiolos (IKZF3) was a milestone in the understanding of their mechanism of action. While recent studies have described the role of IKZF1/3 proteins in multiple myeloma (MM) cells, few have highlighted the significance of IKZF1/3 expression in T-cells.PATIENTS AND METHODS:We analysed the IKZF1/3 expression levels in T-cells from 38 healthy donors (HD), 43 patients with monoclonal gammopathy of undetermined significance (MGUS), 45 patients with asymptomatic MM stage I (MMI) and 50 symptomatic patients with MM stage III (MMIII), diagnosed using Durie-Salmon staging system, by flow cytometry to examine their prognostic and predictive value. We also combined in vivo observations with in vitro assays to determine the effect of IKZF1/3 expression on the T-cell immunophenotype and anti-tumour T-cell response in 162 MMIII patients.RESULTS:Flow cytometry analyses revealed marked differences in the frequency of T-cells expressing IKZF1/3 proteins in patients with different plasma cell diseases, patients with MMIII exhibited significantly higher IKZF3 expressing cells than HD, MGUC and MMI patients (Figure 1.A). We found that high IKZF3, but not IKZF1, expression in T-cells correlates with superior overall survival in MMIII patients treated with immunomodulatory drugs (thalidomide, lenalidomide and pomalidomide, Figure 1.B). Moreover, we show that higher IKZF3 expression in T-cells inhibits myeloma-specific T-cell response in vitro (Figure 1.C) and patients with high IKZF3 expression exhibit increased T-cell response to lenalidomide compared to patients with low IKZF3 expression (Figure 1.D). We also show that the immunophenotype of newly diagnosed MMIII patients with high IKZF3 expressing T-cells frequency shows features of immunodeficiency that are contrary to the changes induced by immunomodulatory drugs (Figure 1.E). Although we observed higher IKZF3 expression in T-cells from patients with MMIII compared to MMI, IKZF3 expression was unaffected by the tumour microenvironment.CONCLUSION:In conclusion, IKZF3 expression in T-cells is a predictive value for clinical outcome in MMIII patients treated with immunomodulatory drugs due to its profound modulation of T-cell functionality.An accompanying immunological study to registered GMMG study ID: NCT02495922:https://clinicaltrials.gov/ct2/show/NCT02495922 [Display omitted] DisclosuresAwwad:Bristol-Myers Squibb: Other: Travel, Accommodations, Expenses. Kriegsmann:BMS: Research Funding; Celgene: Research Funding. Hillengass:BMS: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; honoraria from Amgen, BMS, Celgene: Honoraria; Takeda: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Raab:Celgene: Consultancy, Honoraria; Novartis: Consultancy, Research Funding; BMS: Consultancy, Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Munder:Consultancy: Janssen-Cilag, BMS, Takeda, Amgen, Celgene.: Consultancy; Celgene: Consultancy; Amgen: Consultancy; BMS: Consultancy; Takeda: Consultancy. Weisel:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Salwender:Takeda: Honoraria; Amgen: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Honoraria and travel support: Janssen Cilag, Celgene, BMS.: Honoraria, Other: Travel support. Hänel:Novartis: Honoraria; Roche: Honoraria. Fenk:Honoraria and travel grants: Celgene, Janssen, BMS; research funding: Celgene.: Honoraria. Dürig:Lead Discovery Center: Research Funding. Goldschmidt:Chugai: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millenium: Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Morphosys: Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Hundemer:Research Support BMS, Celgene, Sanofi, Morphosys.: Research Funding.

Clinical Features and Prognostic Factors of Patients with Multiple Myeloma

To summarize the clinical and Laboratory characteristics of patients with multiple myeloma (MM) and analyze the prognostic factors. Two hundred MM patients were retrospectively analyzed for the following parameters, including peripheral blood, bone marrow morphology, cytogenetics, clinical staging, and response to the chemotherapy in order to summarize related factors affecting overall survival (OS). The prognostic factors were also analyzed. 200 patients with MM were divided into 3 groups according to bone marrow plasma cell percentage (BMPC%) in bone marrow smears: ＜10% group (74 cases, 37.0%), 10%-50% group (75 cases, 37.5%), ＞50% group (51 cases, 25.5%). Compared with the other two groups, patients in BMPC%<10% group were characterized by lower clinical staging levels, lower rates of 13q14 deletion and t(11;14) positive, better response to chemotherapy and favorable three-year OS rate. The univariate analysis showed that prognostic factors indicating favorable outcome as evaluated by OS included age≤55 years old, BMPC%＜10%, WBC＜7.5×109/L, Hb≥68 g/L, PLT≥150×109/L, β2-MG＜5.5 mg/L, LDH≤230 U/L, Durie-Salmon staging A, achievement of VGPR or better outcome after the first chemotherapy, achievement VGPR or better outcome after the fourth chemotherapy, and presence of autologous hematopoietic stem cell transplantation(auto-HSCT)(P<0.05). The multivariate analysis showed that prognostic factors indicating favorable outcome as evaluated by OS included age≤55 years old, BMPC%≤50%, WBC＜7.5×109/L, Hb≥68 g/L, achievement of VGPR or better outcome after the fourth chemotherapy (P<0.05). The clinical characteristics are different among MM patients with different BMPC% in bone marrow smears at initial diagnosis, and prognostic analysis shows that the BMPC% in bone marrow smears has an effect on OS rate. BMPC% in bone marrow smears at initial diagnosis, age, WBC, Hb, response to the fourth chemotherapy are also the main factors impacting the prognosis of patients.

Whole Body Low Dose Computed Tomography (WBLDCT) Can Be Comparable to Whole-Body Magnetic Resonance Imaging (WBMRI) in the Assessment of Multiple Myeloma.

Aim of the study is to compare the agreement between whole-body low-dose computed tomography (WBLDCT) and magnetic resonance imaging (WBMRI) in the evaluation of bone marrow involvement in patients with multiple myeloma (MM). Patients with biopsy-proven MM, who underwent both WBLDCT and WBMRI were retrospectively enrolled. After identifying the presence of focal bone involvement (focal infiltration pattern), the whole skeleton was divided into five anatomic districts (skull, spine, sternum and ribs, pelvis, and limbs). Patients were grouped according to the number and location of the lytic lesions (<5, 5–20, and >20) and Durie and Salmon staging system. The agreement between CT and MRI regarding focal pattern, staging, lesion number, and distribution was assessed using the Cohen Kappa statistics. The majority of patients showed focal involvement. According to the distribution of the focal lesions and Durie Salmon staging, the agreement between CT and MRI was substantial or almost perfect (all κ > 0.60). The agreement increased proportionally with the number of lesions in the pelvis and spine (κ = 0.373 to κ = 0.564, and κ = 0.469–0.624), while for the skull the agreement proportionally decreased without reaching a statistically significant difference (p > 0.05). In conclusion, WBLDCT showed an almost perfect agreement in the evaluation of focal involvement, staging, lesion number, and distribution of bone involvement in comparison with WBMRI.

Circular RNA_0000190 and its target microRNA-767-5p are dysregulated, and they are related to risk stratification as well as prognosis in multiple myeloma patients.

This study aimed to explore the correlation between circular RNA_0000190 (circ_0000190) and microRNA-767-5p (miR-767-5p), and their correlations with biochemical indices, risk stratification, treatment response, and survival in multiple myeloma (MM) patients. Bone marrow (BM) plasma cells of 86 MM patients (during standard diagnostic procedures) and 30 healthy donors (HDs) (examination of the eligibility for BM transplantation) were obtained, among which circ_0000190 and miR-767-5p expressions were detected using reverse transcription quantitative polymerase chain reaction. In MM patients, Durie-Salmon stage and International Staging System (ISS) stage were assessed. Clinical responses (including complete response (CR) and objective response rate (ORR)) were assessed. The progression-free survival (PFS) and overall survival (OS) were calculated. Circ_0000190 was decreased, but miR-767-5p was increased in MM patients compared with HDs. Circ_0000190 was negatively correlated with miR-767-5p in both HDs and MM patients. In MM patients, circ_0000190 was negatively correlated with ISS stage, serum creatinine, beta-2-microglobulin, and lactate dehydrogenase but was positively correlated with albumin. Whereas an opposite trend in miR-767-5p was observed. Regarding clinical response, circ_0000190 had the value for predicting increased ORR, while miR-767-5p had the value for predicting decreased CR and ORR. Circ_0000190 high expression was correlated with better PFS and OS, while miR-767-5p high expression was correlated with worse PFS and OS. Multivariate Cox's analyses revealed circ_0000190 high expression as an independent factor predicting better OS. Circ_0000190 and its target miR-767-5p are dysregulated, and they are related to risk stratification and prognosis in MM patients.

Pleural effusion-based nomogram to predict outcomes in unselected patients with multiple myeloma: a large single center experience.

Pleural effusion (PE) is prevalent in unselected "real-life" populations of multiple myeloma (MM). However, its prognostic value on MM is currently elusive. This study aimed to explore the role of PE on MM prognosis and to develop a novel prognostic nomogram for a cohort of Chinese patients with MM. Patients diagnosed with MM form 2000 through 2017 were retrospectively enrolled. PE was evaluated by chest computed tomography (CT) scans. Independent predictors of overall survival (OS) were identified using a multivariable Cox regression model performed on variables selected by the least absolute shrinkage and selection operator (LASSO) algorithm. A nomogram was constructed based on these variables. The concordance index (C-index) and the calibration curve were used to evaluate the predictive performance of the nomogram. Among 861 patients analyzed, 368 patients developed PE. Multivariate cox regression and restricted mean survival time (RMST) analyses revealed that patients with PE experienced worse OS vs. patients without PE. A nomogram predictive of OS was constructed using PE, plasma cell proportion, international staging system (ISS) stage, Charlson comorbidity index (CCI), 1q21 gain, and autologous hematopoietic stem cell transplantation (HSCT). The nomogram showed satisfactory discrimination in the derivation cohort (C-index=0.729) and the validation cohort (C-index=0.684), outperforming the Durie-Salmon (DS) and ISS staging systems. Moreover, the nomogram accurately classified patients into two distinct high- and low-risk groups. PE is frequently encountered in the disease course for MM patients. We derivated and validated a novel nomogram for MM based on PE, outperforming the DS/ISS staging systems.

Characteristics and outcomes of patients with multiple myeloma at the Uganda Cancer Institute.

Data on multiple myeloma (MM) in sub-Sahara Africa is scarce. In Uganda, there is a progressively increasing incidence of MM over the years. We performed a retrospective study on 217 patients with MM at the UCI using purposive sampling method. The objectives of the study were to determine the clinical characteristics, treatment outcomes, 5 year overall survival and predictors of survival of patients with MM at the UCI from 01 January 2008 to 31 December 2012. There were 119 (54.8%) males; the mean(SD) age of the study population at presentation was 59(12.8) years; 183(84.3%) patients presented with bone pain, and 135 (61.9%) had skeletal pathology; 186(85.3%) were HIV negative, and 152(70%) had Durie-Salmon stage III. The median overall survival was 2.5 years, (95% CI, 0.393-0.595); factors significantly associated with worse survival were Durie-Salmon stage III disease, HR=5.9, 95% CI (1.61 - 21.74; P=0.007) and LDH >225 U/L HR=3.3, 95% CI (0.57 - 5.92; P=0.029). Most patients with multiple myeloma at the UCI were diagnosed at a relatively young age, presented with late stage disease and bone pain, and had a shorter survival time. Factors associated with worse survival were Durie-Salmon stage III and LDH >225 U/L.

Association of Growth Differentiation Factor-15 Polymorphisms and Growth Differentiation Factor-15 Serum Levels with Susceptibility to Multiple Myeloma in a Chinese Population.

The aim of our study was to evaluate the relationship between growth differentiation factor-15 (GDF15) rs1058587, rs4808793, and rs1059369 polymorphisms, serum concentrations of GDF15, and International Staging System (ISS) staging or Durie-Salmon staging system (DS) staging in multiple myeloma patients and whether its polymorphism affects the expression of serum GDF15 in Chinese population. A total of 120 patients with multiple myeloma and 119 healthy controls were included in the study. The SNaPshot technique was used to detect the GDF15 gene polymorphisms. Serum GDF15 levels were measured using an Enzyme-Linked ImmunoSorbent Assay (ELISA) kit. There was no significant difference in genotype distribution or allele frequency of three loci between multiple myeloma patients and healthy controls. However, the genotype distribution and allele frequencies of rs1059369 in ISS stage I were significantly different from those in ISS stage II (p = 0.008), and the distribution of rs1058587 genotype was different between ISS stage II and ISS stage III (p = 0.014). The overall serum concentration of GDF15 and the same genotype at the same locus (rs1058587: GC, GG; rs4808793: CC, GC; rs1059369: AA, AT, and TT) in patients with multiple myeloma was significantly higher than in the healthy control group (all p < 0.05). Our results showed the genotype distribution and allele frequencies of rs1059369 and rs1058587 of GDF15 gene have some association with ISS and DS stage. But the polymorphism of GDF15 did not affect the expression of serum GDF15 in patients with multiple myeloma.