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Type 2-diabetes (T2D) is thought to be a relevant risk factor for multiple myeloma (MM), but the relationship between both traits is still not well understood. Thus, we decided to conduct a population-based case-control study in a population of 1420 MM patients (705 women and 715 men) and 1858 controls (916 women and 942 men) to evaluate whether 58 genome-wide association studies (GWAS)-identified common variants for T2D influence the risk of developing MM. Logistic regression analyses showed that carriers of the KCNQ1rs2237892T allele or CDKN2A-2Brs2383208G/G, IGF-1rs35767T/T and MADDrs7944584T/T genotypes had an increased risk of MM (OR=1.32, 95%CI 1.01-1.71, P=0.039; OR=1.86, 95%CI 1.12-3.11, P=0.016; OR=2.13, 95%CI 1.35-3.37, P=0.001 and OR=1.33, 95%CI 1.06-1.67, P=0.014, respectively) whereas those carrying the KCNJ11rs5215C, KCNJ11rs5219T and THADArs7578597C alleles or the FTOrs8050136A/A and LTArs1041981C/C genotypes showed a decreased risk for the disease (OR=0.85, 95%CI 0.73-0.99, P=0.38; OR=0.84, 95%CI 0.72-0.99, P=0.034; OR=0.81, 95%CI 0.68-0.98, P=0.032; OR=0.78, 95%CI 0.64-0.95, P=0.013; and OR=0.76, 95%CI 0.58-0.99, P=0.042, respectively). The associations of these T2D-related variants with an increased or decreased risk of MM were due to non-diabetogenic alleles, which suggests a non-diabetogenic mechanism underlying the effect of these variants to determine the risk of the disease. A gender-stratified analysis also revealed a significant gender effect modification for ADAM30rs2641348, and NOTCH2rs10923931 SNPs (Pinteraction=0.001 and 0.0004 and Phet=0.19 and 0.60, respectively), which also underlies the importance of considering gender as a factor modifying the risk for MM. Men harbouring the ADAM30rs2641348C and NOTCH2rs10923931T alleles had a decreased risk of MM (OR=0.71, 95%CI 0.54-0.94, P=0.015 and OR=0.66, 95%CI 0.50-0.86, P=0.0019) whereas an opposite but not significant effect was observed in women. Finally, SNP-SNP interaction analysis revealed overall significant two- and three-locus interaction models to increase the risk of MM (FAM148Brs11071657-KCNJ11rs5219, and SLC30A8rs13266634-KCNJ11rs5219-FTOrs8050136; P=0.01 and 0.001, respectively) whereas a significant four-locus model was also found to increase the risk of MM in men (FADS1rs174550-TSPAN8rs7961581-PROX1rs340874-KCNJ11rs5219, P=0.001). Although further studies in independent populations are warranted to replicate these findings, these results suggest that TD2-related variants may influence the risk of developing MM, likely through non-diabetogenic mechanisms. Abstract 2044. Table 1. Demographical characteristics of IMMEnSE cases and controls. CASES CONTROLS Region* Gender M/F (Total) Mean Age (± STD) Gender M/F (Total) Mean Age (± STD) Control type Italy 117/107 (224) 62.60±9.90 127/105 (232) 58.75±10.92 General population Poland 173/198 (371) 62.35±10.39 124/226 (350) 50.68±19.43 Blood donors Spain 139/133 (272) 63.06±11.04 218/192 (410) 63.12±11.94 Hospitalized subjects France 42/33 (75) 55.80±9.04 95/89 (184) 44.07±15.22 Blood donors Portugal 32/35 (67) 65.79±11.16 52/42 (94) 60.88±07.88 Blood donors Hungary 49/87 (136) 65.83±11.19 50/51 (101) 73.18±10.10 Hospitalized subjects Denmark 163/112 (275) 55.20±07.32 276/211 (487) 43.26±11.84 General population Total 715/705 (1420) 61.06±10.57 942/916 (1858) 53.56±16.45 Table 2. Selected type-2 diabetes-related polymorphisms Gene name dbSNP rs# Gene name dbSNP rs# ADAM30 rs2641348 JAZF1 rs864745 ADAMTS9 rs4607103 KCNJ11 rs5215 ADCY5 rs11708067 rs5219 ADRA2A rs10885122 KCNQ1 rs2237897 ARAPI, CENTD2 rs1552224 rs2074196 BCL11A rs10490072 rs2237892 CDC123 rs12779790 rs2237895 CDKAL1 rs7754840 KCNQ1OT1 rs231362 CDKN2A-2B rs564398 LTA rs1041981 rs10811661 MADD rs7944584 rs2383208 MCR4 rs12970134 COL5A1 rs4240702 MTNR1B rs1387153 CRY2 rs11605924 NOTCH2 rs10923931 DCD rs1153188 PKN2 rs6698181 EXT2 rs1113132 PPARG rs1801282 FADS1 rs174550 PRC1 rs8042680 FAM148B rs11071657 PROX1 rs340874 FLJ39370 rs17044137 RBMS1 rs7593730 FTO rs8050136 SLC2A2 rs11920090 G6PC2 rs560887 SLC30A8 rs13266634 GCK rs1799884 TCF2 rs7501939 GCKR rs1260326 TCF7L2 rs7903146 HHEX rs1111875 TCF7L2 rs12255372 HMGA2 rs1531343 THADA rs7578597 HNF1A, TCF1 rs7957197 TP53INP1 rs896854 IGF1 rs35767 TSPAN8 rs7961581 IGF2BP2 rs4402960 VEGFA rs9472138 IL13 rs20541 WFS1 rs734312 IRS1 rs2943641 rs10010131 Disclosures No relevant conflicts of interest to declare.

Background: Genome wide association studies (GWAS) have recently identified 8 loci identified with multiple myeloma (MM) susceptibility. We hypothesized that germ line genetic variants may also affect MM progression. We performed the first GWAS of MM survival, by conducting a meta-analysis of two existing studies at University of California San Francisco (UCSF) and the Mayo Clinic, and replicating findings in the International Multiple Myeloma rESEarch (IMMEnSE) consortium. Methods: The UCSF study included 353 MM patients genotyped on an Illumina Omni5 and Illumina 660 array. The Mayo clinic study included 239 MM patients genotyped on an Affymetrix 6.0 array. We imputed missing genotypes using the 1000 Genomes dataset and performed a GWAS for survival using proportional hazards models adjusting for age and gender and genetic ancestry using principal components analysis. We conducted a meta-analysis of the results from the two GWAS. We replicated the top SNPs in the IMMEnSE cohort which included 772 patients with survival data from 7 European countries and one North American site. We used the dataset from Grundberg et al (Nat Genetics 2012) to test for an association between SNPs associated with survival and gene expression in immortalized lymphocytes. We used gene expression data from Zhan et al (Blood 2006) to analyze the association between expression and survival. Results: In meta-analysis, we found a genome wide significant association between SNPs on a region at 16p13 and survival (rs72773978; p=2.9x10e-10). Patients with the minor allele were at increased risk for mortality (HR 2.73; 95% CI: 1.99 - 3.73). The top associated SNPs were all in strong linkage disequilibrium and were centered over the gene FOPNL. We replicated the association in the IMMEnSE cohort and found a significant association between the top SNP from the discovery dataset (rs72773978 p=0.037). We used previously published data to determine the association between gene expression and the top associated SNPs from the GWAS. The top SNP (rs72773978) was not in previously published eQTL databases, so we used rs7201759 which was also associated with survival in our data (p=3.8x10e-10) as a proxy. The minor allele for this SNP was associated with increased levels of expression of FOPNL (p=9x10e-5), but not with expression of any other genes within a 1 megabase region. Finally, we also observed an association between increased expression of FOPNL and shorter survival (HR: 2.62 per standard deviation.; 95% CI: 1.08 - 6.32). Conclusion: Germ line variants at 16p13 near the FOPNL gene are associated with survival among MM patients. FOPNL is thought to be involved in centrosomal function, and centrosomal activity has previously been associated with survival in MM patients. Our results support this previous observation. Furthermore, they suggest that germ line variants could also be useful in assessing prognosis for patients with MM. Citation Format: Elad Ziv, Eric Dean, Donglei Hu, Alessandro Martino, Daniel Serie, Daniele Campa, Blake Aftab, Paige Bracci, Gabriele Buda, Jennifer Caswell, Charles Dumontet, Marek Dudziński, Laura Fejerman, Alexandra Greenberg, Scott Hunstman, Artur Jurczyszyn, Krzysztof Jamroziak, Shaji Kumar, Herlander Marques, Thomas Martin, Joaquin Martinez-Lopez, Vincent Rajkumar, Juan Sainz, Annette Juul Vangsted, Marzena Watek, Jeffrey Wolf, Susan Slager, Federico Canzian, Celine Vachon. Genome wide association study identifies variants at 16p13 associated with survival in multiple myeloma patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5078. doi:10.1158/1538-7445.AM2014-5078

Abstract 5014 Exposure to toxic compounds and pesticides leads to an increased risk to develop Multiple Myeloma (MM). The metabolism and the excretion of xenobiotics are mediated by the enzymes and transporters acting in the detoxifying/elimination process. The nuclear receptors NR1I2 (or PXR) and NR1I3 (or CAR) act as xenosensor activating the detoxifying/elimination process in response to the intracellular levels of xenobiotics. It has been hypothesized that part of the individual variability in drug metabolism efficiency could be due to the genetic variations within these regulator genes affecting their expression and/or function. To investigate the impact of genetic variation within these genes on MM susceptibility, we selected and genotyped 10 tag Single Nucleotide Polymorphisms (SNPs) in the PXR gene and 7 tag SNPs in the CAR gene in 627 MM cases (320 males and 307 females) and 883 (459 males and 424 females) controls from different European populations. All the SNPs were in Hardy-Weinberg equilibrium (p>0.001), with the exception of the PXR SNP rs2461818 that was therefore excluded from the analysis. We found no association of any of the genotyped SNPs with MM risk. In the same way, haplotype distribution showed no differences between cases and controls. This was the first comprehensive investigation of genetic variation in xenobiotic regulators genes PXR and CAR in relation to MM risk and our data suggest that common variants in these genes have no impact in modifying MM risk. Table I. Genotype distribution of the PXR and CAR SNPs among MM cases and controls. SNP (rs) Cases (%) Controls (%) OR* 95%C.I. p-value p-trend PXR C/C 429 (69.5) 623 (70.7) 1.00 Ref 0.423 rs10511395 A/C 160 (25.9) 228 (25.9) 1.02 0.81 – 1.30 0.851 A/A 28 (4.6) 30 (3.4) 1.38 0.81 – 2.35 0.232 PXR C/C 452 (74.0) 656 (74.8) 1.00 Ref 0.451 rs1054190 C/T 137 (22.4) 200 (22.8) 1.00 0.78 – 1.28 0.993 T/T 22 (3.6) 21 (2.4) 1.56 0.84 – 2.88 0.155 PXR C/C 412 (65.9) 591 (67.2) 1.00 Ref 0.819 rs11917714 C/T 190 (30.4) 250 (28.5) 1.07 0.85 – 1.35 0.535 T/T 23 (3.7) 38 (4.3) 0.84 0.49 – 1.44 0.536 PXR C/C 223 (36.3) 296 (33.7) 1.00 Ref 0.126 rs12488820 C/T 289 (47.0) 407 (46.4) 0.93 0.74 – 1.18 0.574 T/T 103 (16.7) 175 (19.9) 0.79 0.58 – 1.06 0.119 PXR G/G 430 (69.6) 593 (67.4) 1.00 Ref 0.807 rs13071341 A/G 166 (26.9) 269 (30.6) 0.85 0.67 – 1.07 0.158 A/A 22 (3.5) 18 (2.0) 1.70 0.90 – 3.22 0.102 PXR A/A 352 (58.7) 516 (39.4) 1.00 Ref 0.981 rs3237359 A/G 209 (34.8) 291 (33.5) 1.04 0.83 – 1.30 0.720 G/G 39 (6.5) 62 (7.1) 0.90 0.59 – 1.37 0.619 PXR C/C 255 (41.2) 383 (43.6) 1.00 Ref 0.815 rs13059232 C/T 299 (48.3) 390 (44.4) 1.16 0.93 – 1.44 0.192 T/T 65 (10.5) 106 (12.0) 0.94 0.66 – 1.33 0.711 PXR A/A 300 (48.7) 437 (49.7) 1.00 Ref 0.258 rs3732357 A/G 240 (39.0) 361 (41.0) 0.94 0.75 – 1.17 0.589 G/G 76 (12.3) 82 (9.3) 1.31 0.92 – 1.85 0.130 PXR T/T 328 (53.6) 463 (52.9) 1.00 Ref 0.424 rs1357459 C/T 249 (40.7) 345 (39.4) 1.02 0.82 – 1.27 0.850 C/C 35 (5.7) 67 (7.7) 0.75 0.49 – 1.17 0.206 CAR A/A 218 (35.4) 335 (38.1) 1.00 Ref 0.571 rs3003596 A/G 296 (48.0) 393 (44.7) 1.16 0.93 – 1.46 0.191 G/G 102 (16.6) 151 (17.2) 1.04 0.77 – 1.41 0.799 CAR G/G 264 (42.7) 371 (42.0) 1.00 Ref 0.642 rs3813627 G/T 276 (44.7) 392 (44.4) 0.98 0.79 – 1.23 0.882 T/T 78 (12.6) 120 (13.6) 0.91 0.66 – 1.26 0.581 CAR A/A 441 (73.1) 635 (73.5) 1.00 Ref 0.911 rs11265571 A/T 147 (24.4) 207 (24.0) 1.01 0.79 – 1.29 0.911 T/T 15 (2.5) 22 (2.5) 0.97 0.49 – 1.89 0.921 CAR T/T 404 (64.2) 575 (65.7) 1.00 Ref 0.836 rs2307418 G/T 193 (31.1) 268 (30.6) 1.02 0.81 – 1.27 0.879 G/G 23 (3.7) 32 (3.7) 1.05 0.60 – 1.83 0.863 CAR C/C 348 (56.6) 508 (57.7) 1.00 Ref 0.527 rs2502805 C/T 220 (35.8) 313 (35.6) 1.05 0.84 – 1.30 0.693 T/T 47 (7.6) 59 (6.7) 1.16 0.77 – 1.74 0.484 CAR A/A 245 (39.8) 346 (39.4) 1.00 Ref 0.770 rs4073054 A/C 291 (47.2) 412 (46.9) 0.98 0.78 – 1.22 0.855 C/C 80 (13.0) 120 (13.7) 0.94 0.68 – 1.31 0.720 CAR C/C 360 (57.6) 524 (59.8) 1.00 Ref 0.391 rs4233368 A/C 225 (36.0) 302 (34.4) 1.09 0.88 – 1.36 0.439 A/A 40 (6.4) 51 (5.8) 1.15 0.74 – 1.78 0.538 Genotype distribution among MM cases and controls in the overall population. * OR are adjusted for age, gender and region of origin. Differences in samples numbers are due to failures in genotyping. Disclosures: No relevant conflicts of interest to declare.

Abstract 2481 Poster Board II-458 Objective: With the pressure on healthcare budgets, it has become increasingly important for healthcare decision makers to consider the value for money of the treatments they reimburse. The objective of this analysis was to evaluate the long term outcomes and costs of rituximab in combination with cyclophosphamide/vincristine/prednisolone chemotherapy regimen (R-CVP) versus CVP alone, in previously untreated patients with indolent Non-Hodgkin Lymphoma (NHL) from the Portuguese National Health System (NHS) perspective. Methods: Cost-effectiveness (Life Years Gained - LYG) and cost-utility analysis (Quality Adjusted Life years – QALYs) were performed for a time horizon of 10 years, according to a Markov economic model with three health states (“progression free survival”, “progression” and “death”) and monthly cycles for a population of previously untreated patients with indolent NHL. Data from a phase III clinical trial (Marcus 2007) was used and expanded to include unpublished 53-month median follow-up data. Survival after first-line therapy was estimated from the Scotland and Newcastle Lymphoma Group registry data and utilities were derived from a study in the UK performed in patients with follicular lymphoma. Resource consumption was estimated by a Portuguese expert panel (Delbecq Panel). Costs were calculated from the Portuguese NHS perspective through official data with prices updated to 2008. Only direct medical costs were considered. Costs and clinical outcomes were discounted at 5% per annum. Deterministic and probabilistic sensitivity analysis were performed around assumptions on the time horizon, costs, utilities and excess mortality rate due to progression applied in the base-case analysis. Results: The 10-year base-case analysis showed a lower total cost per patient with CVP alone (€ 85,838) in comparison with R-CVP (€ 87,774). Life expectancy and quality-adjusted life expectancy per patient were higher with R-CVP (6.361 and 4.166, respectively) than with CVP alone (5.557 and 3.438, respectively), representing increases of 0.804 in LYG and 0.728 (8.7 months) in QALYs gained. The incremental cost per LYG was € 2,407 and the incremental cost per QALY gained was € 2,661. The probabilistic sensitivity analysis confirmed the robustness of the base-case analysis results. Conclusions: This study demonstrates that the combination R-CVP in previously untreated non-Hodgkin lymphoma patients improves life expectancy and is a cost-effective alternative to CVP in Portugal. Disclosures: Braga: Roche Farmacêutica Química, Lda: Employment. Pereira:Roche Farmacêutica Química, Lda.: Employment.

The first line treatment regimen differs according to the type of lymphoma. ABVD for Hodgkin’s Lymphomas (HL) and CHOP or R-CHOP for non-Hodgkin’s Lymphomas (NHL) are the most worldwide used treatments. There is good evidence that reduction in relative dose intensity (RDI) results in loss of clinical benefit. The aims of this study were to define predictive risk factors for the RDI reduction and to evaluate patterns of Granulocyte-Colony Stimulating Factors (G-CSF) use in these first line treatment regimens. Retrospective data from three Portuguese centres of 133 patients (pts) with NHL and HL treated with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), R-CHOP 21 like (rituximab, cyclophosphamide, vincristine, doxorubicin/mitoxantrone, prednisolone) and CHOP 21 like regimens was collected. Dose Intensity Evaluation Programme (DIEP®) software was developed to allow calculation of RDI and includes demographic data, clinical and treatment characteristics, chemotherapy dose modifications and delays, haematological toxicities and patterns of use of G-CSF. Three classes were defined for “size of tumoral mass” (< 5 cm, 5–10 cm, >10 cm) and for “G-CSF administration” (primary prophylaxis, secondary prophylaxis and neutropenia/febrile neutropenia treatment). Univariate and multivariate analyses were performed to identify factors related to RDI ≤ 90% of standard. A P-value < 0.05 was considered for statistical significance. Patient distribution according to lymphoma is HL – 37.6%, NHL – 62.4%. All HL pts were treated with ABVD regimen. Among NHL pts, only 9.9% had a T-cell related lymphoma, 43.7% were treated with CHOP 21 like and 56.3% with R-CHOP 21 like. Median RDI was 92.0% in ABVD, 92.4% in CHOP 21 like and 92.3% in R-CHOP like. RDI ≤ 90% was delivered in 37.1% of all pts. According to the univariate analysis there was no statistical significant difference between RDI (cut-off 90%) and treatment regimen, body mass index, body surface area, serum LDH, albumin, hemoglobin, type of lymphoma, Ann Harbor Staging, symptoms, existence of secondary extranodal involvement, organ with primary involvement, IPI, FLIPI and G-CSF administration. A significant reduction of RDI was associated with age ≥ 65 years, female gender, size of tumoral mass (< 5 cm), bone marrow involvement, hospitalization and presence of a primary extranodal lymphoma. In multivariate analysis, the independent predictor of RDI ≤ 90% was hospitalization (P=0.018). Twenty per cent of R-CHOP 21 like pts were hospitalized due to febrile neutropenia (representing all febrile neutropenia hospitalizations in the study). Six per cent of ABVD pts and 12.1% of CHOP like pts were hospitalized due to other reasons.G-CSF was administrated as primary prophylaxis to 3.33% of the pts treated with ABVD regimen, 12.5% of CHOP 21 like pts and 5.71% of the R-CHOP 21 like pts. The proportion of pts receiving G-CSF as secondary prophylaxis was: ABVD - 80%, CHOP 21 like – 75% and R-CHOP like – 60%. Administration of G-CSF due to neutropenia or febrile neutropenia was performed to 93.33% of ABVD regimen pts, 81.25% of CHOP 21 like pts and 85.71% of R-CHOP 21 like pts. Differences in the reduction of RDI in lymphoma pts treated with the three distinct regimens were not significant. However, hospitalizations in general were statistically associated with RDI reduction. In this study, a relation was found between R-CHOP 21 like regimen and hospitalization due to febrile neutropenia. These results may indicate that R-CHOP 21 like regimen pts could be candidates for primary G-CSF prophylaxis.

OBJECTIVE: Evaluate costs and benefits of rituximab in combination with cyclophosphamide/vincristine/prednisolone chemotherapy regimen (R-CVP), in previously untreated patients with indolent non-Hodgkin lymphoma (NHL), compared to CVP alone from a Portuguese National Health System (NHS) perspective. METHODS: Cost-effectiveness (Life Years Gained--LYG) and cost-utility analysis (Quality Adjusted Life Years--QALYs) were performed for a time horizon of 10 years, according to a Markov economic model with three health states (progression free survival, progression and death) and monthly cycles for a population of previously untreated patients with indolent NHL. Data from a phase III clinical trial was used and expanded to include unpublished 53-month median follow-up data. Survival after first-line therapy was estimated from the Scotland and Newcastle Lymphoma Group registry data and utilities were derived from a study in the UK performed in patients with follicular lymphoma. Resource consumption was estimated by a Portuguese expert panel (Delbecq Panel). Costs were calculated from the Portuguese NHS perspective through official data with prices updated to 2008. Only direct medical costs were considered. Costs and clinical outcomes were discounted at 5% per annum. Deterministic and probabilistic sensitivity analysis were performed around assumptions on the time horizon, costs, utilities and excess mortality rate due to progression applied in the base-case analysis. RESULTS: The 10-year base-case analysis showed a lower total cost per patient with CVP alone (€ 85,838) in comparison with R-CVP (€ 87,774). Life expectancy and Quality adjusted life expectancy per patient were higher with R-CVP (6.361 and 4.166, respectively) than with CVP alone (5.557 and 3.438, respectively), representing increases of 0.804 in LYG and 0.728 (8.7 months) in QALYs gained. The incremental cost per LYG was € 2,407 and the incremental cost per QALY gained was € 2,661. The probabilistic sensitivity analysis confirmed the robustness of the base-case analysis results. CONCLUSIONS: This study demonstrates that the combination R-CVP in previously untreated indolent NHL patients improves life expectancy and is a cost-effective alternative to CVP in Portugal.

We established the IMMEnSE (International Multiple Myeloma rESEarch) consortium, to increase our understanding of the genetic determinants of multiple myeloma (MM) risk, response to therapy and survival. At present we have DNA samples of over 3200 MM cases and 3000 healthy controls from 10 countries, mainly in Europe. For the majority of the cases clinical data on known prognostic factors, therapy outcome and survival have been also collected. We already performed several association studies in the context of the IMMEnSE consortium. In particular, associations were found between MM risk and SNPs in the ABCB1 gene, which encodes for an efflux pump that has a key role in protecting cells from chemical damage (rs10264990: odds ratio (OR) =0.79, 95% confidence interval (CI) 0.68-0.91; p=0.001, and rs17327442: OR=1.99; 95%CI 1.32-3.02; p=0.001). We also investigated the 8q24 region, which has been shown to harbor multiple loci of susceptibility to various cancers, and found an association between a SNP mapping in this region and MM risk (rs2456449: OR=1.37; 95%CI 1.12-1.68; p=0.0022). In addition, IMMEnSE cases and controls were also genotyped for three MM risk SNPs from the first genome-wide association study (GWAS), and the association of two of them (rs4487645 on chromosome 7p15.3 and rs6746082 on chromosome 2p23.3) was confirmed. Finally, SNPs of key telomere-related genes were genotyped and telomere length was measured in MM cases and controls, and a pleiotropic and functional variant of the TERT gene was found to be associated with reduced MM risk (rs2242652: OR=0.81; 95%CI 0.72-0.92; p=0.001). A suggestive association between longer telomeres and increased MM risk was also found (ptrend=0.01). We will study new SNPs emerging as promising candidates from ongoing GWAS on MM risk and survival, as well as SNPs of key genes involved in the pathogenesis of MM. Finally, we plan to study methylation status of key genes involved in MM etiology, and mitochondrial copy number. The role of all these factors will be investigated in relation to MM risk and prognosis. Collection of samples and data of MM cases and controls is ongoing, as well as of subjects with monoclonal gammopathy of undetermined significance (MGUS). Table 1. MM cases and healthy controls collected in the IMMEnSE consortium Country Cases Median age(5th-95th percentile) Controls Median age(5th-95th percentile) Control type Italy 232 63 (46-78) 237 59 (42-76) General population Poland 1,286 63 (42-82) 200 68 (43-79) Blood donors Spain 322 64 (46-82) 1,131 66 (43-84) Hospitalized subjects France 642 57 (37-68) 191 48 (18-63) Blood donors Portugal 70 68 (45-82) 100 58 (53-79) Blood donors Hungary 148 68 (34-90) 105 74 (55-87) Hospitalized subjects Denmark 348 56 (43-65) 1,000 63 (52-73) Blood donors Israel 109 60 (41-77) 95 - Blood donors Canada 62 58 (42-70) - - - Japan 51 66 (47-84) - - - Total 3,270 63 (37-84) 3,059 63 (18-92) Figure 1 Centers involved in IMMEnSE Figure 1. Centers involved in IMMEnSE Disclosures No relevant conflicts of interest to declare.

The research project is designed to create new ways of looking at the story of a city; the focus is to present elements of the city as an art gallery space. Mapping technologies are used to present information as an aesthetic image. This project will add the emotional context of the moment and location as part of the information aesthetic. The story of a city is an ongoing timeline of interconnected exchanges, thoughts and ideas. The stories and ideas used in this project can be taken from any point in the timeline and presented together as information aesthetics.\ud Datum will be recorded via image motion capture and audio technologies to create image and soundscapes. made from the shape of letterforms. When the audio fi le is read back into a sonogram the sound wave created is in the\ud shape of the letterform. Further research will look at creating typefaces based on the sound the letterform makes instead of any visual aesthetic. Content will be presented in various ways, using digital and traditional formats. The artwork can be displayed in situ via web based geo tagging and augmented reality platforms on mobile devices, plus physical representations of this work as printed and sculptural forms.