Higher Incidence Of Multiple Myeloma Research Articles

Abstract P05: Testing patterns and referrals for monoclonal protein detection at John Peter Smith hospital

Abstract Background: Multiple myeloma (MM) is an incurable disease. Blacks have a higher incidence of MM and are diagnosed at a younger age compared to other populations. Safety-net hospitals (SNH) treat a high proportion of Black patients. Early detection of myeloma is important to prevent permanent organ dysfunction. Serum monoclonal protein testing using expanded panel aids in the diagnosis and monitoring of monoclonal gammopathies. This test result has 16 discrete components and any out-of-range value can be confusing to the ordering providers, triggering referrals to hematology oncology (hemonc). We sought to identify the testing and referral patterns at John Peter Smith (JPS) Hospital, a SNH in North Texas. Methods: Data was obtained from JPS Data Analytics and Reporting department. All serum monoclonal protein expanded panel (LAB174) orders and results for patients tested from 1-1-2022 to 12-31-2022 were abstracted from EPIC EMR. Demographic information was collected along with details about ordering providers and referrals. We sorted the data and excluded all orders by oncology providers as well as all inpatient orders. Data analysis was completed using Excel. Results: A total of 1063 tests were performed on 1026 patients. 39% were Non-Hispanic White (NHW), 36% were Black, and 13% were Hispanic. Median age was 57 years. Monoclonal band was seen in 143 (13%) samples; immunoglobulin (IG) kappa (k) 59, IG lambda (λ) 68, both IG k and IG λ 9. Results with gamma (γ) and beta (β) band were seen in 22 and 3 respectively. Measurable k band (>0.1 g/dL) was seen in 12 tests, > 1 g/dL in 5, and > 3 g/dL in only 1 test. Measurable λ band seen in 9 tests, > 1 g/dL in 3, and > 3 g/dL in no tests. Serum protein electrophoresis (SPEP) was normal in 525, and immunofixation (IFE) was normal in 507. Polyclonal SPEP was noted in 169 tests. Hypogammaglobinemia was seen in 11. 72 out of 369 (20%) Blacks had abnormal bands vs 47 out of 397 (12%) NHW. Two-tailed t-test was significant at p-value 0.00327. Referrals were generated to hemonc in 201 patients. Rheumatology accounted for 19% of tests, nephrology 18%, neurology 19%, and remaining were from primary care and other specialties. 212 patients were referred to hematology oncology using ICD10 diagnosis code R77.8. Rheumatologists referred 48 patients, which is 25% of all patients that they tested. Referrals from neurology: 39 (20%) and nephrology: 25 (13%). Conclusions: At JPS, clinical care providers are conducting tests to identify precursor conditions to myeloma. The test positivity rate was 13% in the non-oncology outpatient setting. Blacks had a higher percentage of positivity, reinforcing the need for a higher index of suspicion. The complexity of the test results, however, is overwhelming to the ordering providers, triggering referrals to the hemonc division, prompting recruitment and training of midlevel providers within hemonc to ensure proper monitoring of patients with precursor conditions. JPS Office of Clinical Research is planning to participate in early detection clinical trials for myeloma. Citation Format: Kavya Athipatla, Melissa Howell, Anuradha Lingam, Kayani Narra. Testing patterns and referrals for monoclonal protein detection at John Peter Smith hospital [abstract]. In: Proceedings of the Blood Cancer Discovery Symposium; 2024 Mar 4-6; Boston, MA. Philadelphia (PA): AACR; Blood Cancer Discov 2024;5(2_Suppl):Abstract nr P05.

Eliminating Racial Disparities Among Transplant Patients in Multiple Myeloma after Referral to a Tertiary Center

Introduction: Autologous stem-cell transplantation (ASCT) remains an integral part of therapy for many newly diagnosed and relapsed multiple myeloma (MM) patients. Most tertiary centers rely on age, ECOG status, and multi-organ function evaluation to determine eligibility for ASCT. African Americans (AA) have a higher incidence of monoclonal gammopathy of undetermined significance (MGUS), higher incidence of MM and higher mortality rates than their Caucasian counterparts, mainly due to lower access to care. Furthermore, AA patients are also underrepresented in clinical trials. Studies have shown AA patients have similar to improved progression-free survival (PFS) and overall survival (OS) compared to Caucasian patients when similar therapies are offered to both groups; however, lower rates of transplantation are reported among AA patients. This is likely multifactorial in origin, with varying risk factors, biological influences, and social hindrances leading to racial disparity. We sought to examine the differences in rates of ASCT among African Americans vs Caucasian patients. Methods: We conducted a retrospective chart review of all patients with myeloma referred to our center between 2018 and 2022. Information regarding demographics, referral information, insurance and transplant status obtained for all patients referred and/or transplanted at our center were obtained from this chart review. The diagnosis date was obtained from referral records if they were referred from an outside institution. All patients received therapy at the discretion of treating physicians. Statistics are descriptive. Results: 206 AA patients were referred to our center for transplant evaluation, of which 138 underwent autologous transplantation (67%). Additionally, 141 Caucasian patients were referred to us for transplant evaluation, 98 of which underwent ASCT (69%). The transplant rates were similar across both genders among AA patients, with female AA patients accounting for 49% of all AA transplants. Among Caucasian patients, female patients accounted for 37% of all Caucasian transplants. The median referral delay time was 104 days among AA patients and 85 days among Caucasian patients. The median time from the date of referral to transplant was 128 days for AA patients and 124 days for Caucasian patients. The reasons for non-transplant varied between the two races. For African Americans, the most common reason was medical contraindication followed by patient disinterest in contrast to Caucasian patients, which was patient disinterest followed by medical contraindication. Conclusion: Once referred to a tertiary center, we observed no racial disparities among transplants in AA and Caucasian patients. While the median time from the date of referral to the date of transplant was similar across both groups, we noted an increased referral delay among AA patients.

Exposure to Fine Particulate Matter (PM2.5) Is Associated with Worse Multiple Myeloma Outcomes in a Large, Urban, Multi-Ethnic Cohort

Introduction Outdoor air pollution (OAP) is a complex mixture, primarily consisting of black carbon (BC), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and particulate matter with an aerodynamic diameter of less than 2.5 microns (PM2.5). OAP is typically generated by the combustion process from motor vehicles, fossil fuel burning and industrial waste. The potential impact of air pollutants on cancer outcomes has not been systematically studied in communities of color. Multiple Myeloma (MM) is a hematologic malignancy defined by the clonal expansion of plasma cells leading to subsequent monoclonal protein expression resulting in multiple complications including anemia, renal disease, significant bone pain and increased fracture risk. MM is the second most common hematologic malignancy. The US Surveillance, Epidemiology, and End Results (SEER) registry estimates 34,000 new cases diagnosed and 13,000 deaths annually from MM. Risk factors for multiple myeloma include race, BMI, and occasionally genetic predisposition. Blacks and Hispanics were shown to have a higher incidence of MM that of non-Hispanic whites (Kaur G et al Clin Lymphoma Myeloma Leuk. 2021). There is recent evidence to suggest that environmental exposures, OAP in particular, may play a role in propagating disease progression in multiple myeloma (Landgren O JAMA Oncol 2015). A recent study demonstrated that first responders to the World Trade Center disaster had a higher rate of developing myeloma precursor disease (MGUS) and an earlier age of developing multiple myeloma (Landgren O JAMA Oncol. 2018). Our study seeks to further characterize patterns of exposure to OAP in patients with MM. Methods A retrospective cohort was developed of patients diagnosed with Multiple Myeloma at Montefiore Health System (Bronx, NY) between 1997-2018 (n=1608), using the Montefiore Electronic Data Warehouse. Of those patients, 1525 were identified as having 1 st cancer diagnosis of MM. Patient addresses (n=1514) were then used to geospatially overlay with OAP and Organic Matter from 2000-2018 using land use regression models. Ground-level PM2.5 was estimated by combining Aerosol Optical Depth (AOD) retrievals from the NASA MODIS, MISR, and SeaWIFS instruments with the GEOS-Chem chemical transport model, and subsequently calibrated to regional ground-based observations of both total and compositional mass using Geographically Weighted Regression (Hammer M.S et al Environ. Sci. Technol. 2020). This initial analysis focuses specifically on PM2.5, which was summarized as the number of years each patient was exposed to levels higher than the EPA standard of 12ug/m 3 and if the patient experienced an average PM2.5 >12ug/m 3 across their entire follow-up in the cohort. Additional information regarding demographics, dates of diagnosis and certain clinical parameters (Hgb, Cr, albumin, etc) were extracted. Differences in PM2.5 exposures, and clinical parameters, were compared by race and ethnicity using t-tests and chi-squared tests. Cox proportional hazards regression estimated the risk of death during follow-up associated with PM2.5 exposure, adjusting for confounders. Results Our patient population was highly diverse. Patients were 21% White, 50% Black with 27% having Race classified as Other. Thirty percent were Hispanic. Age at mean diagnosis was 66.24 years. On average, Bronx MM patients had higher exposure to PM2.5 than the EPA safe standard of 12 µg/m 3 from years 2000-2007 and the WHO safe standard of 5 µg/m 3 in all years of follow-up. Improved overall survival among our Multiple Myeloma patients was associated with fewer number of years exposed to PM2.5 >12 µg/m 3 (Hazard Ratio (HR)=1.12, 95% Confidence Interval (CI)=0.99- 1.27), when adjusting for sex and race. Further adjustment for smoking status yielded similar results (HR = 1.13, 95%CI = 0.98-1.30). Conclusion In this large urban, multi-ethnic cohort of MM patients, many patients experienced annual exposures to PM2.5 that were higher than the EPA and WHO safe standards of 12 µg/m 3 and 5 µg/m 3. Overall survival in MM patients was associated with fewer years of exposure to PM2.5, suggesting that reducing exposure to environmental pollutants, particularly OAP for our patients may lead to better outcomes. Additional analyses are needed to better understand the impact of treatment and clinical factors, as well as the other air pollutants in this patient population.

Impact of Race on Progression-Free Survival and Overall Survival in Patients with Multiple Myeloma

Background: Multiple myeloma (MM) is a disorder of plasma cells. Management typically includes induction therapy, autologous stem-cell transplantation (ASCT) and maintenance therapy. Despite significant progress in treatment modalities and improved survival and response rates in patients diagnosed with MM, it remains an incurable disease with a poor outcome, especially in high-risk groups. Black patients have been shown to have a higher incidence of MM than white patients. Multiple studies have been done to examine racial disparities among white and black patients, specifically in overall survival (OS) and progression free survival (PFS). However, data has been overall inconclusive with some studies suggesting there is a difference in survival based on race, while other studies suggesting the opposite. Thus, racial disparities among white and black patients' needs to be further investigated. In our retrospective chart review we reviewed all adult patients with advanced MM within Henry Ford Cancer Institute in the last 10 years to determine the impact of maintenance therapy on PFS and overall survival OS. Methods: We conducted a retrospective chart review of adult patients with MM who underwent autologous stem cell transplantation (ASCT) between January 1, 2012 to December 31, 2022. Those who received maintenance chemotherapy after transplant were included in the study. Patients who were lost to follow-up or who had largely incomplete records were excluded. Data points including age, gender, race, date of transplant, maintenance chemotherapy regimen, last follow-up, and date of death (if applicable) were recorded. Kaplan-Meier plots were used to illustrate overall survival and time to relapse between various races. Statistical significance was set at p<0.05. Results: There were 158 patients included in the study. Of the 158 patients, 82 (51.9%) were male, and 76 (48.1%) were female. The average age of patients included was 61.66 + 9.30 years, spanning from 32 to 78 years old. There were 71 (44.9%) White patients, 76 (48.1%) Black patients, and 11 (7.0%) patients that were of another race. There was no statistical significance in PFS and OS between Black, White and Other race categories. Conclusions: We did not see a difference in outcome based on race and believe all patients would derive equal benefit from maintenance therapy. Further prospective studies are warranted to examine racial disparities in patients with multiple myeloma.

The role of obesity on autologous bone marrow transplant and post-transplant outcomes

Background/Aim: Autologous hematopoietic cell transplantation (AutoHCT), administered at high doses, has improved survival rates among patients with refractory or recurrent lymphoma and multiple myeloma (MM). However, inconsistencies in defining obesity, varying body weight ranges, and heterogeneous patient populations have been examined. Some researchers have hypothesized that significantly overweight patients face a higher risk of transplant-related complications. This study investigates the association between body mass index (BMI), obesity, and autologous peripheral stem cell mobilization. Methods: A retrospective evaluation of data from 180 patients who underwent peripheral stem cell mobilization at our clinic between 2014 and 2020 was conducted. Excluding patients under 18 years of age, the primary objective was to assess how BMI influences autologous transplant outcomes and mortality. This retrospective cohort study aimed to determine whether obesity constitutes an independent risk factor for autologous bone marrow transplantation. Results: Among the patients, the most prevalent diagnosis (47.2%) was MM, with notable differences in incidence rates across BMI categories (P=0.039). Obesity and overweight were associated with a higher incidence of MM (47.2%), whereas normal and underweight individuals had predominantly been diagnosed with DLBCL (44.2%). Significant differences in CD34 cell counts were observed among BMI groups (P=0.033). Overweight and obese individuals exhibited lower CD34 cell counts than underweight/normal groups (P=0.033). The treatment group showed significantly higher CD34 cell counts than the G-CSF alone group (P=0.046). Female gender (P=0.022), PLT engraftment (P=0.024), post-chemo-mobilization hospital-stay duration (P=0.019), and G-CSF count were identified as mortality risk factors (P=0.017). Conclusions: This investigation found no adverse correlation between mortality and weight among patients with various hematological malignancies undergoing AutoHCT. Obesity alone should not be a contraindication for proceeding with AutoHCT in clinically warranted hematological malignancy treatment, as no significant survival differences were observed among overweight, obese, and normal-weight individuals.

Analysis of racial and ethnic disparities in multiple myeloma US FDA drug approval trials

AbstractAfrican Americans (AAs) have a higher incidence of multiple myeloma (MM) than White patients. Mortality is also higher in AAs compared with White patients. AAs more commonly have immunoglobulin H translocations t(11;14) and t(14;16) compared with White patients. We sought to characterize the demographic representation in MM clinical trials and evaluate outcomes based on race and ethnicity. We conducted a pooled analysis of all trials submitted to the US Food and Drug Administration (FDA) to support approval of a MM therapeutic between 2006 and 2019. Demographic characteristics were analyzed descriptively. An age-adjusted stratified Cox regression model was used to evaluate the relationship between time-to-event outcomes and race and ethnicity. Nineteen global trials comprising 10 157 patients were pooled. White, Asian, and Black patients comprised 84%, 7%, and 4% of the dataset, respectively; Hispanic patients comprised 4%. The age-adjusted overall survival hazard ratio (HR) for Black compared with White patients was 0.89 (95% confidence interval [CI], 0.75-1.05). The age-adjusted HR for US Black vs US White patients was 0.82 (95% CI, 0.66-1.02). For rest-of-world (RoW) Black vs RoW White patients, the HR was 1.31 (95% CI, 0.97-1.77). Black and Hispanic patients were underrepresented in the trials supporting FDA approval of MM drugs. Black patients were primarily enrolled in the United States. Outcomes in US patients were more favorable compared with those in patients in the RoW. Given the higher incidence of MM in AAs and the different disease characteristics, efforts should be made to improve representation of AAs in MM clinical trials.

Similar Survival for African American and Caucasian Multiple Myeloma Patients Receiving Auto-SCT

INTRODUCTIONAfrican Americans (AA) have higher incidence of multiple myeloma (MM), younger age at presentation, delays in starting therapy, and inadequate referral for auto-SCT compared to other races (Bhatnagar, V et al; Cancer 2015). However, prior studies are conflicted about AA patients' clinical outcomes if they have access to the same treatment as Caucasians. Herein, we evaluated survival endpoints for AA and Caucasian MM patients who underwent auto-SCT at a single center. METHODSWe retrospectively analyzed patients with MM who underwent first auto-SCT between July 2013 and October 2016. July 2017 was the cut-off for survival data. Clinical features, MM therapies (pre- and post-transplant), treatment responses, and transplant outcomes were compared between AA and Caucasian patients. Continuous variables were compared using the t-test. Categorical variables were compared using the Fisher's exact test. Overall survival (OS) and progression-free survival (PFS) functions were estimated by the Kaplan-Meier method. Plausible risk factors for OS and PFS were assessed by the Cox regression model. RESULTSA total of 169 patients with MM were included (46% AA, 54% Caucasian). Patients' demographics are listed in Table 1. There were possible differences in race distribution. More AA were women (60% versus 45%, p=0.06), AA had intermediate cytogenetic risk based on fluorescent in situ hybridization (FISH) at diagnosis (47% versus 25%, p=0.06), and more AA had BMI > 25 kg/m2 (88% versus 77%, p=0.07). However, all p-values are of marginal statistical significance. AA patients were younger at auto-SCT with a median age of 57 years (range: 39-71) versus 60 (range: 42-74, p=0.01). AA had lower hemoglobin levels at transplant with 60% being at or below 10 g/dL versus 43% (p=0.03). Twenty-six percent of AA had progressive disease prior to transplant versus 11% (p=0.02) and subsequently had a longer time from diagnosis to auto-SCT with a median of 0.82 years (range: 0.39-4.03) versus 0.74 (range: 0.21-4.8, p=0.04). Among those receiving multiple induction regimens, 68% of AA had experienced progressive disease prior to transplant compared to 34% (p=0.02) and had slightly longer time from diagnosis to transplant with a median of 1.43 years (range: 0.57-4.03) versus 0.88 (range: 0.56-4.8, p=0.06). There were no racial differences in initial induction therapy type, best response prior to transplant, maintenance therapy, creatinine level at transplant, or ECOG score, and stage based on the ISS or isotype at diagnosis. Fifty-six of the patients progressed (36% of AA, 31% of Caucasian) and 22 expired (17% of AA, 10% of Caucasian). Univariate Cox regression showed significantly greater hazard of death (HR: 4.55, 95% CI: 1.93, 10.72, p=0.0005) for those with prior progressive disease. Those receiving multiple regimens prior to transplant had 2.4 times higher hazard of death (95% CI: 1.04, 5.54, p=0.04) compared to those receiving single induction regimen. Results of the univariable models did not indicate significantly different hazards of death (HR:1.69, p=0.23) or progression (HR:1.12, p=0.67) for AA when compared to Caucasians. CONCLUSIONEven though AA patients experienced more disease progression prior to transplant and greater time to transplant than Caucasians, there were no significant differences in overall survival or progression-free survival between races. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Initial Whole-Genome Sequencing of Plasma Cell Neoplasms in First Responders and Recovery Workers Exposed to the World Trade Center Attack of September 11, 2001.

The World Trade Center (WTC) attack of September 11, 2001 created an unprecedented environmental exposure to known and suspected carcinogens. High incidence of multiple myeloma and precursor conditions has been reported among first responders to the WTC disaster. To expand on our prior screening studies, and to characterize the genomic impact of the exposure to known and potential carcinogens in the WTC debris, we were motivated to perform whole-genome sequencing (WGS) of WTC first responders and recovery workers who developed a plasma cell disorder after the attack. We performed WGS of nine CD138-positive bone marrow mononuclear samples from patients who were diagnosed with plasma cell disorders after the WTC disaster. No significant differences were observed in comparing the post-WTC driver and mutational signature landscapes with 110 previously published WGSs from 56 patients with multiple myeloma and the CoMMpass WGS cohort (n = 752). Leveraging constant activity of the single-base substitution mutational signatures 1 and 5 over time, we estimated that tumor-initiating chromosomal gains were windowed to both pre- and post-WTC exposure. Although limitations in sample size preclude any definitive conclusions, our findings suggest that the observed increased incidence of plasma cell neoplasms in this population is due to complex and heterogeneous effects of the WTC exposure that may have initiated or contributed to progression of malignancy.

Lifetime Pesticide Use and Monoclonal Gammopathy of Undetermined Significance in a Prospective Cohort of Male Farmers.

Background:Farmers have a higher incidence of multiple myeloma, and there is suggestive evidence of an elevated prevalence of its precursor, monoclonal gammopathy of undetermined significance (MGUS), relative to the general population. Pesticide exposures are suspected to play a role; however, the biologic plausibility for associations with multiple myeloma remains unclear.Objectives:Our objectives were to examine the prevalence of MGUS and evaluate associations with a wide range of pesticides in a large sample of farmers.Methods:We obtained sera and assessed MGUS among 1,638 male farmers of age in the Agricultural Health Study (AHS), a prospective cohort in Iowa and North Carolina. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed to estimate associations with MGUS for recent use (within the 12 months before phlebotomy) and cumulative intensity-weighted lifetime days of use of specific pesticides.Results:The age-standardized MGUS prevalence was significantly elevated among AHS farmers (7.7%) compared with demographically similar men in the National Health and Nutrition Examination Survey (2.8%) or Olmsted County, Minnesota (3.8%; ). Recent use of permethrin was associated with MGUS [recent use vs. no recent use, (95% CI: 1.06, 3.13)], especially among those who had also used it in the past [recent and past use vs. never use, (95% CI: 1.32, 4.69)]. High intensity-weighted lifetime use of the organochlorine insecticides aldrin and dieldrin was associated with MGUS relative to those who never used either of these pesticides [ (95% CI: 1.29, 4.54); ]. We also observed a positive association with high lifetime use of petroleum oil/distillates as an herbicide, as well as an inverse association with fonofos use.Discussion:This is the largest investigation of MGUS in farmers and the first to identify an association with MGUS for permethrin, a pyrethroid insecticide previously associated with multiple myeloma. Given the continued widespread use of permethrin in various residential and commercial settings, our findings may have important implications for exposed individuals in the general population. https://doi.org/10.1289/EHP6960

НЕКОТОРЫЕ ВОПРОСЫ ЭПИДЕМИОЛОГИИ, ПАТОГЕНЕЗА, ДИАГНОСТИКИ И ЛЕЧЕНИЯ МНОЖЕСТВЕННОЙ МИЕЛОМЫ

A literature review article provides a comprehensive overview of literature related to epidemiology, pathogenesis, diagnosis and treatment of multiple myeloma (MM). Literature data show that MM has unclear patterns of the disease distribution, and there are trends in rising incidence. Although the aetiology of MM is not fully understood, according to most researchers, risk factors (RFs) leading to a progressively high incidence of MM include advanced age, male gender, exposure to harmful environmental factors (ionising radiation, chemical agents), family predisposition, an increased prevalence of autoimmune diseases and obesity. MM is characterised by the absence of specific clinical manifestations and similarity with other conditions, which is one of the factors associated with delay in diagnosis of MM. Damage to internal organs, particularly the heart and kidneys, a frequent complication of MM, leads to mutual burdening and is also one of the factors of adverse outcomes early during the disease. The International Myeloma Working Group (IMWG) diagnostic criteria and additional investigation techniques allow high accuracy to diagnose MM and its complications. Despite the development and introduction of new drugs and treatments, the long-term survival rates in MM patient remains low. Therefore there is a need for further research in this direction. Keywords: Multiple myeloma, cardiorenal complications, diagnostics, free light chains of immunoglobulins, treatment.

Initial Whole Genome Sequencing of Plasma Cell Neoplasms in First Responders and Recovery Workers Exposed to the World Trade Center Attack of September 11, 2001

Initial Whole Genome Sequencing of Plasma Cell Neoplasms in First Responders and Recovery Workers Exposed to the World Trade Center Attack of September 11, 2001

African American Patients With Multiple Myeloma: Optimizing Care to Decrease Racial Disparities.

The incidence of multiple myeloma in African Americans is two to three times higher than in other ethnicities and is the leading hematologic malignancy in African Americans. Despite the high incidence of multiple myeloma in African American individuals, a vast majority experience delays in diagnosis and reduced usage of effective therapies, including stem cell transplantation, as well as low participation in clinical trials. Racial disparities, social and financial health disparities, and barriers to earlier access to care can lead to poorer patient outcomes. There are also unique characteristics in the disease manifestation in African Americans with multiple myeloma that are imperative for oncology nurses to understand and recognize to provide optimal care.

Superior Survival in African American Patients Who Underwent Autologous Stem Cell Transplantation for Multiple Myeloma

Introduction/BackgroundAfrican American (AA) individuals have a twofold higher incidence of multiple myeloma (MM) compared with other racial groups. Outcomes are affected by factors such as disparate access to care as well as differences in disease biology. Patients and MethodsWe conducted a single-institution analysis to evaluate the effect of AA race on outcomes of MM patients who underwent autologous stem cell transplantation (ASCT) in the pre-novel and novel agent era. ResultsSixty-one (47%) patients were AA and 69 (53%) were non-AA. Overall, 78 (60%) patients received any novel agent before transplantation and 52 (40%) received only chemotherapy. More non-AA patients received initial induction with a proteasome inhibitor (40 [60%] vs. 17 [28%]; P = .0007), and were treated with post-ASCT maintenance therapy (28 [41%] vs. 14 [23%]; P = .04). Time from diagnosis to ASCT in AA patients was 10 (range, 4-144) versus 8 (range, 3-54) months in non-AA patients (P = .01). Despite this, treatment-free survival (TFS) was equivalent between the 2 groups (x vs. y). Furthermore, AA patients had greater median overall survival (OS) compared with non-AA patients (not reached vs. 108 months; P = .03) and significantly improved OS in multivariable Cox proportional hazards models (adjusted hazard ratio, 0.30; 95% confidence interval, 0.11-0.81; P = .017). Median OS, landmarked at the time of relapse, was improved in AA patients (not reached vs. 68 months for P = .05). ConclusionOur study showed with long follow-up, equivalent TFS after ASCT in AA and non-AA patients yet improved OS. Post relapse survival is improved in AA patients suggesting a better response to salvage therapy.

Genomic Abnormalities Among African Individuals with Monoclonal Gammopathies Using Calculated Ancestry

Monoclonal gammopathies, including multiple myeloma (MM), represent a group of plasma cell (PC) disorders that comprise of mostly incurable hematopoietic malignancies with an increasing incidence in the US. Previous epidemiological studies demonstrated a 2-3 fold higher incidence of monoclonal gammopathy of undetermined significance (MGUS) and a similarly higher incidence of MM along with a ~4-year younger age of onset among African Americans (AA) compared to European Americans (EAs) (Fonseca, Leukemia, 2017). This suggests a possible ancestral-associated genetic predisposition of AAs to the development of monoclonal gammopathies (Landgren, Blood, 2006). When access to care is equal, AAs have a better overall survival compared to EAs suggesting that AAs may have a genetic predisposition that renders them better responders to treatment or have more favorable cytogenetic subtypes of MM (Waxman, Blood, 2010). Previous efforts to understand this disparity have relied on self-reported race rather than genetic ancestry. We hypothesize that quantifying genetic ancestry is necessary to fully understand the genetic mechanisms of racial disparities of monoclonal gammopathies. We describe our study of 881 patients with monoclonal gammopathies who had undergone uniform testing to identify MM-specific cytogenetic abnormalities. DNA from the bone marrow samples was genotyped on the Precision Medicine Research Array. Biogeographical ancestry was assessed using the Geographic Population Structure Origins tool, which provides the ancestral breakdown of 36 admixture components for each individual representing different geographic regions and outputs admixture proportions corresponding to those ancestries (Elhaik, Nat Commun, 2014). We evaluated whether an increase in the percentage of African Ancestry altered the odds of any primary cytogenetic abnormality. We demonstrated that a 10% increase in the percentage of African ancestry was associated with a 6% increase in the odds of detecting either an t(11;14), t(14;16) or t(14;20) (odds ratio = 1.06, 95% CI: 1.02 - 1.11; p-value = 0.05). Although we observed an increase in the odds of each of the individual translocations with 10% increase in African ancestry, l t(11;14) (OR=1.03) t(14;16) (OR=1.11) and t(14;20) (OR=1.10), these three abnormalities were combined to achieve greater statistical power. The differences in cytogenetic abnormalities were most striking among individuals with ≥80.0% African (n=120) compared to individuals with We complement our past studies that relied on self-reported race and characterized patients9 demographic and uniformly collected cytogenetic data in relation to genetically defined African ancestry. We demonstrate the prevalence of having one of three specific subtypes (i.e., t(11;14), t(14;16), or t(14;20)) was significantly higher in those with highest (≥80%) compared to lowest ( Disclosures Elhaik:DNA Diagnostics Center: Consultancy. Baird:DNA Diagnostics Center: Employment. Cerhan:Jannsen: Other: Scientific Advisory Board; Nanostring: Research Funding; Celgene: Research Funding. Stewart:Amgen Inc., BMS, Celgene, Takeda, Roche, Seattle Genetics, Janssen, Ono: Consultancy; Amgen Inc., Celgene, Roche, Seattle Genetics: Research Funding. Dispenzieri:Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK: Research Funding. Kumar:Novartis: Research Funding; KITE: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity9s Board of Directors or advisory committees; AbbVie: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity9s Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity9s Board of Directors or advisory committees; AbbVie: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Roche: Research Funding.

Abstract A27: Diversity in multiple myeloma clinical trials

Abstract Background: Multiple myeloma (MM) accounts for approximately 1% of all cancers and 10% of hematologic malignancies in the United States (U.S.). MM occurs in all races, but the incidence in African Americans is two to three times higher than in non-Hispanic whites. MM is also slightly more frequent in men than women (1.4:1). Many clinical trials lack appropriate representation of specific patient populations, limiting the generalizability of the evidence obtained. Therefore, we determined the representation of ethnic minorities, the elderly, and women in MM clinical trials. Methods: Enrollment data from all therapeutic trials reported as completed in clinicaltrial.gov from 2000 to 2016 were analyzed. Clinical trials including other hematologic malignancies and with recruitment outside of the U.S. were excluded. Enrollment fraction (EF) was defined as the number of enrollees divided by the 2013 SEER database MM complete prevalence. Chi-square test was used to estimate differences in categorical data. Results: Out of 177 MM clinical trials (CT), 78 (44%) reported ethnicity with a total of 12,055 enrollees. Regarding enrollees' ethnic composition, 84% were non-Hispanic White (NHW), 8.6% African American (AA), 2.8% Asian, 1.8% Hispanic, and 0.1% Native American/Alaskan Indian. Out of those 78 CT, 52 (66%) were phase II, 15 (19%) phase III, and 11 (14%) phase I. Most of the results were published from 2012 to 2016 (74%). Forty-six (59%) trials were sponsored by industry, 7 (9%) by NCI, and 25 (32%) were investigator initiated. Participation in CT varied significantly across ethnic groups, NHW were more likely to be enrolled in CT (EF of 0.23) than AA (EF of 0.08, p < 0.0001) and Hispanics (EF of 0.05, p< 0.0001). Males had a higher recruitment rate than females (58% vs. 42%), but this could be explained by the higher incidence of MM in males. Enrollees' median age was 62 years. Younger patients (< 65 years) were more likely to be enrolled in CT than the elderly (66% vs. 34%, p<0.0001). Industry-sponsored trials were less likely to recruit AA compared with investigator-initiated trials (7.6% vs. 12%, p<0.01). Conclusions: Despite the higher incidence of MM in African Americans and the elderly, the former only represented 8.6% of the study participants and 66% of these were less than 65 years of age; therefore, we are lacking data in the tolerability of these new agents in our aging MM population. We also observed that industry studies were less likely to recruit AA patients. Collaborations between investigators, sponsors, and the community are necessary to increase our minority and elderly patients' access to clinical trials. Citation Format: Narjust Duma, Miguel Gonzalez Velez, Jesus Vera-Aguilera, Richardo Parrondo, Veronica Mariotti, Jonas Paludo, Yucai Wang, Ronald Go, Alex Adjei. Diversity in multiple myeloma clinical trials [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A27.

163 - Improved Survival in African American Patients Undergoing Autologous Transplant for Multiple Myeloma in the Chemotherapy and Novel Agent Era

African Americans (AA) have a 2- to 3-fold higher incidence of multiple myeloma (MM) when compared to other racial groups. Evidence suggests that there may be differences in the biology of MM, which confer a more favorable prognosis in AA patients. Prior studies are conflicted as to whether AA patients achieve equal or improved outcomes compared to non-African American (non-AA) patients. Our purpose was to evaluate the impact of AA race on outcomes of MM patients undergoing ASCT at a single center in both the chemotherapy and novel agent era. One hundred and twenty-nine patients who received melphalan 200 mg/m2 and ASCT between 2000 and 2013 were included in the analysis. Sixty-one (47%) patients were African-American and 68 (53%) were non-AA. Baseline characteristics including age, FISH, cytogenetics, paraprotein subtype, median number of prior therapies and International Staging System (ISS) stage were similar between racial groups. Overall, 77 (60%) patients received any novel agent prior to transplant and 52 (40%) received only chemotherapy. More non-AA patients were male (59% vs. 38%, p=0.02), received initial induction with a proteasome inhibitor (59% vs. 28%, p=0.0007), and were treated with post-ASCT maintenance therapy (41% vs. 23%, p=0.008). Time from diagnosis to ASCT in AA patients was 10 (range: 4-144) versus 8 (range: 3-54) months in non-AA patients (p=0.01). The ASCT hospital course was similar between both groups with no significant differences in time to neutrophil and platelet engraftment as well as the duration of hospitalization. Additionally, there was no significant difference in the extra-hematologic toxicity between the two groups including the incidence of diarrhea, mucositis, and infection. Response was measured using the International Myeloma Working Group criteria and was assessed immediately prior to transplant and between 90 to 180 days after transplant. No differences were observed in pre-transplant (p=0.13) or post-transplant (p=0.28) response rates between the two groups. African American patients had a significantly improved median OS compared to non-AA patients (not reached vs. 108 months, p=0.03). We further stratified analyses of OS by those treated in the chemotherapy versus novel agent era. Improved OS was observed in both the chemotherapy (93 vs. 68 months, p=0.02) and novel agent (not reached vs. 79 months, p=0.01) treatment era. In a multivariate Cox proportional hazards model, AA race was associated with improved overall survival (adjusted HR 0.30, 95% CI 0.11 to 0.81; p=0.017). Multiple myeloma has one of the most apparent ethnic disparities in incidence and outcomes among cancers. In our study, AA patients had a longer time to transplant and received less proteasome inhibitor-based induction and post-ASCT maintenance suggesting disparities in access to care. Despite these differences in treatment, we observed improved overall survival after ASCT compared to non-AA patients. We demonstrated this improved OS in patients who had received either chemotherapy or novel agents prior to ASCT. These findings provide further evidence for more favorable outcomes among AA patients. One explanation could be a difference in disease biology that may result in a lower risk disease. Investigation of these biologic differences between AA and non-AA MM patients may increase our understanding of the pathogenesis and future treatments of myeloma. Disclosures No relevant conflicts of interest to declare.

Racial Differences in Long-Term Risk of Venous Thromboembolism Among Older Patients Following Diagnosis and Treatment of Multiple Myeloma

IntroductionIndividuals with multiple myeloma (MM) are at a greater risk of thrombotic complications than those with other cancers. Cancer-related venous thromboembolism (VTE) including pulmonary embolism and deep vein thrombosis is associated with increased morbidity and mortality. Both incidence of MM and VTE differ by race/ethnicity. Blacks have a higher incidence of MM compared to Whites, whereas Asian/Pacific Islanders (API) and Hispanics have a lower incidence. In the general population, the risk of VTE and prevalence of its associated risk factors are higher in Blacks. The hypercoagulable state induced by MM and its treatment could further modify any pre-existing VTE risk in different racial/ethnic groups. Our objective was to describe the incidence of VTE following diagnosis and treatment of MM by race/ethnicity.MethodsWe conducted a retrospective cohort study using data from the Surveillance, Epidemiology, and End Results (SEER) - Medicare linked database. Individuals 66 years or older with myeloma as their first primary malignancy diagnosed between 2001 - 2011 were identified. These individuals were required to have age related eligibility for Medicare, continuous enrollment in the 12 months period prior and post myeloma diagnosis, and Medicare as their primary payer. Using SEER registries and administrative claims, we collected data on race/ethnicity, cancer characteristics and treatment, and chronic comorbidities. VTE events were defined as having an inpatient hospitalization or 2+ outpatient visits with ICD-9 diagnosis codes 415.1x, 451.xx, and 453.xx. Long-term risk of VTE was assessed by determining the annualized incidence of VTE at 12, 24, and 36 months following MM diagnosis. In each 12-month period, MM patients were followed from diagnosis until the earliest of the following: a VTE event, death, or end of 12-month period since diagnosis. Additionally, we calculated VTE incidence rates in the 12-month period following stem cell transplantation for those that received it. Overall and race-specific crude incidence rates with 95% confidence intervals (CIs) were calculated in each period using person-time contributed per observation period. Poisson regression was used to compare age- and gender-adjusted incidence rate ratios (IRRs) and 95% CIs comparing different racial/ethnic groups with White patients.ResultsIn a final analytic cohort of 9,480 patients, most were White (73%) and fewer patients were Black (15%), Hispanic (6%) or API (4%). The median age at diagnosis was 77 years (interquartile range [IQR]: 71-82). Half the cohort (51%) were women, 28% had diabetes and 21% had a history of heart failure at diagnosis. Overall, the median time to first VTE event post-MM diagnosis was 140 days (IQR: 46-409). More patients that developed VTE were female, Black, younger at MM diagnosis, and treated with stem cell transplantation. The overall incidence rate of VTE during the first 12 months following the diagnosis of MM was 170 per 1,000 person-years (95% CI 160-180). Adjusting for age and gender, Blacks had a higher incidence of VTE compared to Whites (IRR 1.24; 95% CI 1.07-1.44) and APIs had a lower incidence (IRR 0.55; 95% CI 0.37-0.81). In the second post-diagnosis year, there were 6,257 individuals remaining that contributed 5,443 person-years. Overall, the incidence rate was 82 per 1,000 person-years (95% CI 75-90). Incidence was greater in Blacks vs. Whites (adjusted IRR 1.25; 95% CI 0.98-1.59). Consistent with findings from the first analysis period, APIs continued to have lower incidence vs. Whites (adjusted IRR 0.44; 95% CI 0.22-0.89). In the third post-diagnosis year, the overall incidence rate was 80 per 1,000 person-years (95% CI 72-89) and any racial disparities observed in age and gender adjusted IRRs were no longer significant. For patients in the first year following stem cell transplantation, annualized incidence rates of VTE were elevated (overall incidence rate of 148, 95% CI 117-188).ConclusionIn this large population-based cohort of older MM patients, we observed racial disparities in the incidence of VTE within the first 24 months of diagnosis. A risk-adapted method of VTE prophylaxis should be considered. Understanding risk factors and groups vulnerable to development of thromboembolic events can help guide clinical decision making regarding VTE prophylaxis. DisclosuresNo relevant conflicts of interest to declare.

Interleukin-32 Induce Production of IL-6 in Multiple Myeloma Bone Marrow Stromal Cells

Background: Multiple myeloma (MM) is closely associated with inflammation. Patients with auto-immune disease history of infection and other inflammatory disease have higher incidence of MM. IL-6 is the most important inflammatory factor in MM which plays a key role in the proliferation and progression. We previously demonstrated that MM cells were modified by bone marrow stromal cells (BMSCs) that formulate a inflammatory microenvironment in bone marrow (BM) and secret IL-6. How the inflammation makes BMSCs secret IL-6, however, remained undocumented. Our subsequent study compared the differential secretion of peripheral blood (PB) between MM patients and normal people by cytokine array, and showed that interleukin 32(IL-32) is highly expressed in MM patients. IL-32, also named natural killer 4(NK-4), is a newly found inflammatory factor. It was reported in solid tumors IL-32 is a pro-inflammatory factor which triggers a massive amplification of inflammatory process resulting in the change of other inflammatory factor including IL-6,IL-10,TNF-α. In this study, we examined BMSCs cytokines in MM BM and found that IL-32 was a functional factor in the process of inflammation in MM BM microenvironment.Results: First, to test our previous study, we detected IL-32 in BM supernatant and PB supernatant in both MM patients (n=45) and healthy controls (n=13) by ELISA. Result showed that in both BM and PB, MM patients have higher expression of IL-32 compared to healthy controls (P<0.05). Next, total BM cells(both CD138+ and CD138- cells) from MM patients were assayed by qRT-PCR for gene expression analysis.IL-32 were highly expressed in MM BM cells and the CD138+ cells (P<0.05). We also detected IL-32 in MM cell lines (RPMI 8226,OPM-2) and BMSCs isolated from MM patients by qRT-PCR, Western blot, and ELISA, and found that IL-32 was highly expressed in MM cell lines than BMSCs. In contrast, proteinase 3(PR3, receptor of IL-32) was highly expressed in BMSCs compared to MM cell lines.Second, we stimulated the MM BMSCs with recombinant IL-32α, and found that the secretion of IL-6,CCL3 (MIP1-α), CCL4(MIP-1β) were significantly increased and CCL-5(RANTES)and IL-10 were decreased (P<0.05). Further, Western blot was applied to detect the inflammation molecular pathway in BMSCs. JAK-STAT pathway and NF-κB pathway were activated, and the phosphorylation of STAT3 was increased. After we knock down the PR3 in BMSCs, these changes were reduced. We repeated these experiments in BMSCs isolated from 15 different MM patients, the phenomenon mentioned above showed in 11 patients. The recombinant IL-32α was also used to stimulate 8226 and OPM-2 cells, but these two kinds of MM cells didn’t secret IL-6, and no significant change in cell proliferation or cell apoptosis.Finally, our group co-cultured the MM BMSCs with 8226 and OPM-2 cells. The secretion of IL-6 and the phosphorylation of JAK-STAT pathway in BMSCs were also increased. Knockdown of IL-32 in 8226 and OPM-2 cells weakened these changes.MM Cell proliferation and cell cycles after co-culture with MM BMSCs are under investigation.Conclusion: our findings suggest that IL-32 is mainly secreted by MM cells. It may not directly promote the MM cells to grow. However, IL-32 promote the MM BMSCs to secret more cytokines including IL-6,CCL3,CCL4 by activating the JAK-STAT3 pathway, which lead to a amplification of inflammation in BM environment, resulting in the cell proliferation . DisclosuresNo relevant conflicts of interest to declare.

Improved Survival in African American Patients Undergoing Autologous Transplant for Multiple Myeloma in the Chemotherapy and Novel Agent Era

African Americans (AA) have a 2- to 3-fold higher incidence of multiple myeloma (MM) when compared to other racial groups. Evidence suggests that there may be differences in the biology of MM, which confer a more favorable prognosis in AA patients. Prior studies are conflicted as to whether AA patients achieve equal or improved outcomes compared to non-African American (non-AA) patients. Our purpose was to evaluate the impact of AA race on outcomes of MM patients undergoing ASCT at a single center in both the chemotherapy and novel agent era.One hundred and twenty-nine patients who received melphalan 200 mg/m2 and ASCT between 2000 and 2013 were included in the analysis. Sixty-one (47%) patients were African-American and 68 (53%) were non-AA. Baseline characteristics including age, FISH, cytogenetics, paraprotein subtype, median number of prior therapies and International Staging System (ISS) stage were similar between racial groups. Overall, 77 (60%) patients received any novel agent prior to transplant and 52 (40%) received only chemotherapy. More non-AA patients were male (59% vs. 38%, p=0.02), received initial induction with a proteasome inhibitor (59% vs. 28%, p=0.0007), and were treated with post-ASCT maintenance therapy (41% vs. 23%, p=0.008). Time from diagnosis to ASCT in AA patients was 10 (range: 4-144) versus 8 (range: 3-54) months in non-AA patients (p=0.01). The ASCT hospital course was similar between both groups with no significant differences in time to neutrophil and platelet engraftment as well as the duration of hospitalization. Additionally, there was no significant difference in the extra-hematologic toxicity between the two groups including the incidence of diarrhea, mucositis, and infection.Response was measured using the International Myeloma Working Group criteria and was assessed immediately prior to transplant and between 90 to 180 days after transplant. No differences were observed in pre-transplant (p=0.13) or post-transplant (p=0.28) response rates between the two groups. African American patients had a significantly improved median OS compared to non-AA patients (not reached vs. 108 months, p=0.03). We further stratified analyses of OS by those treated in the chemotherapy versus novel agent era. Improved OS was observed in both the chemotherapy (93 vs. 68 months, p=0.02) and novel agent (not reached vs. 79 months, p=0.01) treatment era. In a multivariate Cox proportional hazards model, AA race was associated with improved overall survival (adjusted HR 0.30, 95% CI 0.11 to 0.81; p=0.017).Multiple myeloma has one of the most apparent ethnic disparities in incidence and outcomes among cancers. In our study, AA patients had a longer time to transplant and received less proteasome inhibitor-based induction and post-ASCT maintenance suggesting disparities in access to care. Despite these differences in treatment, we observed improved overall survival after ASCT compared to non-AA patients. We demonstrated this improved OS in patients who had received either chemotherapy or novel agents prior to ASCT. These findings provide further evidence for more favorable outcomes among AA patients. One explanation could be a difference in disease biology that may result in a lower risk disease. Investigation of these biologic differences between AA and non-AA MM patients may increase our understanding of the pathogenesis and future treatments of myeloma. DisclosuresNo relevant conflicts of interest to declare.

Abstract IA07: Outcome disparities in multiple myeloma: The role of race/ethnicity

Abstract Approximately 27,000 new cases of multiple myeloma (MM) will be diagnosed and more than 11,000 deaths will occur from it in 2015. Overall, 5-year relative survival rates have improved from 26.5% in 1975 to 44.9% in 2010, and this has been attributed to the introduction of novel therapeutic agents, widespread utilization of autologous stem cell transplant (ASCT), and improvement in supportive care modalities. However, studies evaluating the role of race/ethnicity in MM have shown marked disparities in incidence and outcomes of MM among patients of different racial subgroups. Traditionally, it has been known that African-Americans (AA) have a higher incidence of MM than Whites and that it occurs in AA at a younger age. Despite this difference in incidence, AA patients are known to have a better overall survival (OS) than Whites. Recent population-based outcomes analyses of MM patients beyond just Whites and AA has shown that Asians have the best median OS, while Hispanics have the worst, in a population that is more representative of the current US racial/ethnic mix. Additionally, the cumulative survival benefit over time as per a recent report was most pronounced among Whites (1.3 years) and least among Asians (0.5 years), suggesting a possible differential access as well as utilization of therapeutic modalities. Thus, despite overall improvement in MM outcomes over years, racial disparities exist. While majority of the data so far has reported the existence of these outcome disparities, a few reports have explored the potential causes of these differences. With regards to disease biology, there is some data suggesting that MM patients belonging to different races may have variability in the incidence of high-risk mutations, with AA MM patients having a lower incidence of such mutations, supporting the better OS seen in AA patients as compared to Whites. Another suggestion supporting differences in an interaction between biologic and environmental factors in MM patients is the variability in incidence of second primary malignancies in patients after they have developed MM, which may affect their outcome and OS. Other causes of outcome disparities may include a differential access to certain treatment options, especially more complex ones like stem cell transplants, as well as certain novel therapeutic agents that may depend on the patient's insurance payer status, which brings up differences in socioeconomic status, education level and barriers in accessing healthcare. It has also been reported recently that access to comprehensive cancer centers has benefitted Whites more than racial minorities. While access issues are being reported for MM patients belonging to different races, it has been suggested that outcome disparities by race are not noted in equal access healthcare systems. The potential shortcomings for these studies in equal access healthcare systems though, have been small size, mostly single-institution and focusing primarily on Whites and AA, without much representation yet of Hispanics and Asians, despite these two racial subgroups being the fastest growing ones in the US. Outcome disparities in MM by patient race have been established. The factors affecting these outcome disparities may be complex and interrelated, making it difficult to identify specific factors that may be modifiable. Yet, it is important to explore outcome disparities and their potential causes, especially in large cohorts prospectively, so that healthcare resources may be utilized efficiently and furthermore, the disadvantaged population subgroups may be benefitted by targeted interventions. Citation Format: Sikander Ailawadhi. Outcome disparities in multiple myeloma: The role of race/ethnicity. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr IA07.