Outcomes In African American Patients Research Articles

Allograft Injury and Outcomes in African American Lung Transplant Recipients

African American patients (AA) have poorer outcomes than White patients (W) after heart and kidney transplant. Little is known about differential outcomes in lung transplantation (LTx). This study compares allograft injury and chronic allograft dysfunction (CLAD) in AA and W LTx. The 469 LTx enrolled in two multicenter prospective cohort studies were categorized by self-reported race. Time from transplant to CLAD-free survival adjudicated by a committee using ISHLT standard definitions. Serial post-transplant plasma samples (n=2152) were assayed for %ddcfDNA by shotgun sequencing. Baseline characteristics, post-transplant %ddcfDNA trends, tacrolimus trough levels and CLAD-free survival were compared between AA and W. LTx recipients were 79% W and 14 % AA. Donor-recipient race mismatch was more commonly observed for AA than for W (75.0% vs. 27.3%, p<0.01). Other baseline characteristics were similar in AA and W. During follow-up (median 19.8 months, IQR = 10.7 - 36.9), tacrolimus trough levels were similar in AA and W (9.2±0.1 vs. 9.0±0.1, p = 0.19). However, AA showed 1.5X higher rejection rates (HR = 1.6, CI = 1.0 - 2.6), and higher %ddcfDNA levels particularly beyond 6 months when maintenance immunosuppression doses were lowest (Figure A). Higher %ddcfDNA trends correlated inversely with CLAD-free survival; AA developed CLAD and/or died 18.8 (mean) months before W (Figure B). Similarly, acute rejection was inversely with CLAD-free survival. AA LTx show higher allograft injury and poorer CLAD-free survival than W LTx despite equivalent tacrolimus blood levels. Studies to understand the mechanisms of allograft injury and poor outcomes in AA are warranted across all solid organ transplants.

Abstract P5-07-09: Modeling taxane-induced peripheral neuropathy ex vivo using patient-derived neurons

Abstract Background: Taxane-induced peripheral neuropathy (TIPN) is the most devastating survivorship issue for patients receiving therapy. Dose reductions due to TIPN in the curative setting lead to inferior outcomes for African American patients, as prior research has shown that this group is more susceptible to developing severe neuropathy. The mechanistic underpinnings of TIPN, however, have not been entirely elucidated. While it would be appealing to use primary tissue to study the development of TIPN, procuring nerves from patients is not realistically feasible, as nerve biopsies are painful and may result in permanent damage. Therefore, our laboratory has investigated paclitaxel-induced neuronal morphological and molecular changes using an ex vivo model of human-induced pluripotent stem cell (iPSC)-derived neurons.Methods: iPSCs are undifferentiated and endlessly dividing cells that can be generated from a patient’s somatic cells, such as peripheral blood mononuclear cells (PBMCs). We successfully reprogrammed PBMCs into iPSCs using the Erythroid Progenitor Reprograming Kit (STEMCell TechnologiesTM); pluripotency was verified by flow cytometry analysis. iPSCs were then induced into neurons using a differentiation protocol that bypasses the neural progenitor stage and uses selected small-molecule modulators of key signaling pathways (SMAD, Notch, FGFR1 inhibition and Wnt activation). Results: Flow cytometry analysis revealed expression of core pluripotency transcription factors Nanog, Oct3/4 and Sox2 in iPSCs overlaps with commercially purchased pluripotent cell line UCSD064i-20-2. Trilineage differentiation of iPSCs was confirmed with immunofluorescent imaging with germ-layer-specific markers; Sox17 and ExoA2 for ectoderm, Nestin and Pax6 for mesoderm, and Ncam and Brachyury for endoderm. Sensory neuron markers, β-III tubulin and Peripherin were applied to stain the cells for the maturity of iPSC-derived neurons. Patch-clamp electrophysiology and calcitonin gene-related peptide (CGRP) release data supported functionality of the induced neurons and provided insight into the timing for which downstream assays could be performed (week 4 post-induction). We have also performed a cell viability assay and fluorescence-activated cell sorting (FACS) using four cell-surface markers (CD184, CD44, CD15, and CD24) to select a neuronal population. At least 70% of the cells were viable in the isolated neuron population. Conclusion: We have found that these iPSC-derived neurons recapitulate mature neuronal phenotypes and demonstrate functionality. Thus, this represents a patient derived ex vivo neuronal model to investigate the molecular mechanisms of clinical TIPN. Citation Format: Geneva Cunningham, Erica Cantor, Xi Wu, Fei Shen, Guanglong Jiang, Santosh Philips, Casey Bales, Yucheng Xiao, Theodore R. Cummins, Jill C. Fehrenbacher, Bryan P. Schneider. Modeling taxane-induced peripheral neuropathy ex vivo using patient-derived neurons [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-07-09.

Sodium Excretion and Cardiovascular Outcomes in African American Patients With CKD: Findings From the African American Study of Kidney Disease and Hypertension

Sodium Excretion and Cardiovascular Outcomes in African American Patients With CKD: Findings From the African American Study of Kidney Disease and Hypertension

Clinical Characteristics and Disease Course in Black Patients With Lymphomatoid Papulosis: A Case Series

INTRODUCTION: Lymphomatoid papulosis (LyP) is a CD30+ T-cell lymphoproliferative disorder (LPD) presenting as a recurrent eruption of papules and nodules which resolve spontaneously. CD30+ LPD prevalence in African American (AA)/Black patients is lower compared to White patients. CD30+ LPD has been recently reported to have worse outcomes in AA patients compared to White patients. METHODS: A retrospective chart review identified eight AA patients with LyP. We describe our experience with these eight patients and review the literature on similar cases. RESULTS: In half of the eight included patients, lesions occurred 1-4 years before they were diagnosed. In six patients (75%), resolution of the lesions resulted in hyperpigmented macules and scars. Five patients (63%) had also mycosis fungoides. Most of the patients who were followed (4/7, 57%) did not have complete resolution at their last visit, despite different treatment approaches. Discussion: Our results highlight that although LyP has an indolent course in AA/Black patients, residual hyperpigmentation and scars frequently occur, highlighting the need for better treatments of this lymphoproliferative disorder in this specific population. J Drugs Dermatol. 2020;19(1):89-91. doi:10.36849/JDD.2020.4602

Virologic Clearance of Hepatitis C Is Associated with Improved Outcomes in African American Patients with Lymphoma

Background: Association of hepatitis C virus (HCV) infection and B-cell non-Hodgkin Lymphoma (B-NHL) is well-established. Directly-acting antiviral HCV therapy (DAA) results in very high rates of sustained viral response (SVR) and HCV cure. Studies of the impact of successful antiviral therapy on lymphoma outcomes in HCV-infected patients can have important implications for patient management and for understanding of the biology of different lymphomas. The strongest evidence of positive impact of HCV antiviral therapy on lymphoma regression is available for indolent lymphomas, especially marginal zone lymphoma. Impact of antiviral therapy on HCV-associated aggressive B-NHL is still under investigation. Furthermore, there is no data on outcomes for HCV-associated B-NHL in African-American (AA) patients. The aim of this study was to evaluate lymphoma characteristics and outcomes in HCV-associated B-NHL, in a predominantly AA population. Methods: All consecutive patients with lymphoma and reactive HCV Antibody (HCV Ab+) diagnosed and treated at our center between January 2003 and December 2017 were studied. Patients with HCV-associated mixed cryoglobulinemia without any overt lymphoma, HCV-associated paraproteinemia and patients who did not have antiviral treatment history available were excluded. All information was obtained by review of electronic medical records. Baseline patient characteristics including age, sex, race, comorbidity including HIV infection, lymphoma stage, histology, prognostic score and baseline lactate dehydrogenase (LDH) were recorded. Lymphomas were classified according to the 2016 WHO classification. Prognostic score was calculated using International Prognostic Index (IPI) for aggressive lymphomas, Follicular Lymphoma International Prognostic Index (FLIPI) for indolent lymphomas other than chronic lymphocytic leukemia (CLL) and CLL-IPI for CLL. Details of lymphoma treatment and antiviral therapy were recorded. Virologic clearance (VC) was used to collectively describe both SVR (undetectable HCV RNA 12 weeks after completion of antiviral treatment) and spontaneous clearance of HCV without treatment. Study outcomes were overall response rate (ORR), complete response rate (CR), overall survival (OS) and progression free survival (PFS). Results: We found 397 patients with lymphoma at our institution, of which, 40 patients had HCV. Thirty-eight patients had complete lymphoma and antiviral treatment history available and were included in the analysis. Median age was 58 years, 90% were AA; 68% were men. Diffuse large B-cell lymphoma (DLBCL) was the predominant histology (50%). Advanced stage (64%), aggressive lymphoma (60%), good prognostic score (74%) and elevated LDH (66%) were common. A total of 21 patients were treated, 18 with DAA and 3 with interferon-based therapy. Twenty-two patients had VC, either spontaneous or with antiviral therapy. Patients with VC, had significantly higher ORR (95% vs 69%, RR 2.4, CI95 1.3-4.4, p&lt;0.05) and CR (73% vs 38%, 2.29, CI95 1.1-5.0.0, p&lt;0.05) compared to patients without VC. Median OS was also significantly higher in patients with VC than patients without VC (not reached vs 89 months, RR 0.4, CI95 0.2-0.6, p&lt;0.05) . Median PFS was not significantly different between two groups. We analyzed ORR and CR in subgroups of aggressive lymphoma, indolent lymphoma and DLBCL. Patients with VC had significantly higher CR then patients without VC in the subgroups of aggressive lymphoma and DLBCL (100% vs 46% and 100% vs 45% respectively, p&lt;0.05), while ORR was not different. Conclusions: Hepatitis C VC is associated with improved CR and OS in predominantly AA lymphoma patients including patients with aggressive B-NHL. The precise role and timing of HCV antiviral therapy in HCV-associated aggressive B-NHL should be assessed in large prospective studies that include AA patients. Disclosures No relevant conflicts of interest to declare.

Abstract 4913: Differences in presentation and survival outcomes for African American patients with newly diagnosed multiple myeloma

Abstract Background: Though the incidence of MM is threefold higher in the African American (AA) population compared to Caucasians, reported long term outcomes are less favorable presumably due to inequities in access to healthcare. We have conducted a retrospective analysis of our institutional data of 1000 patients treated with RVD induction therapy, assessing differences in presentation, disease biology, and outcomes in AA patients. Methods: A total of 1000 newly diagnosed MM patients were treated with RVD induction therapy from January 1st 2005 until August 31st 2016. Dose adjustments were made based on physician’s discretion and patient tolerability. Demographic and outcomes data for the patients were obtained from our IRB approved myeloma database and responses were evaluated per IMWG Uniform Response Criteria. Results: 56.4%of patients were white (W), and 33.9% were AA, consistent with the demographic representation of the state of GA and our institutional referral population. Median age was 61 years (range 16-83), 57 for AA patients (range, 24-83) compared to 62 (range, 16-81) in white patients, suggesting the onset is earlier among AA. In regard to stage, AA: 73.9% stage I/II, 26.1% stage III; W: 77.1% stage I/II, 22.9% stage III, showing no difference in prognostic staging at presentation. There was no statistically significant difference in the presenting labs between AA and whites except for hemoglobin, with more AA patients presenting with Hgb≤9.9 g/dL (45.7% AA vs 32.5% W, p &amp;lt;.0001). In terms of prevalence of high-risk cytogenetics, there was no significant difference between the two cohorts in: complex karyotype, t(4;14), t(11;14) or del1p. However, there were significant differences found in the rates of: amp 1q 19.2% W/10.6% AA, (p&amp;lt;.0001), del13 28.3% W/19.6% AA (p=.003), and del17p 11.7% W/7.2% AA (p=.019). There was no significant difference in the number of patients who underwent ASCT (84% W vs 82% AA, p=.241), nor in ≥VGPR rates post-induction and 100 days post-ASCT. Median PFS for the entire cohort was 63 months, 62 months (54-69.9) for white patients versus 65 months (53-76.9) for AA patients (p=0.403). At a median follow up of 38 months, median OS has not yet been reached. Conclusions: This is the largest reported cohort of myeloma patients treated with RVD induction, with one-third of the patients representing the AA population. In our dataset, AAs are diagnosed 5 years younger, with lower hemoglobin at presentation and lower rates of amp1q, del13 and del17p when compared to whites. When offered the same induction regimen and opportunity for ASCT, AAs tend to experience the same survival benefits as their white counterparts. The lack of significant difference in PFS or OS suggests standardization and improved access to care could lead to better long-term outcomes in the AA population. Note: This abstract was not presented at the meeting. Citation Format: Nisha Joseph, Vikas A. Gupta, Craig Hofmeister, Charise Gleason, Leonard T. Heffner, Kafuman L. Jonathan, Lawrence H. Boise, Madhav D. Dhodapkar, Sagar Lonial, Ajay K. Nooka. Differences in presentation and survival outcomes for African American patients with newly diagnosed multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4913.

242-OR: Do GLP-1RA and SGLT2i Reduce Cardiovascular Mortality in African-American Patients with Type 2 Diabetes? A Meta-analysis

While patients enrolled in the cardiovascular safety trials (CVST) for GLP-1RA and SGLT2i were mostly whites, the ADA’s updated recommendations are being generalized to all races. This raises a controversial question regarding the ability to generalize CVST results to African American (AA) patients. We searched MEDLINE, EMBASE, and CENTRAL looking for CVST comparing diabetic medications to placebo in type 2 diabetes and reporting a statistically significant lower incidence of either the primary outcome of MACE or any of the pre-specified secondary outcomes. We then extracted cardiovascular outcomes for AA patients. Sensitivity and subgroup analyses were performed according to the class of diabetic medications. We included 6 trials (GLP-1RA in 4; SGLT2i in 2). While those trials enrolled 53,978 patients, only 2794 were AA. There was no significant difference in CV outcomes between diabetic medications (GLP-1RA or SGLT2i) and placebo in AA patients (RR [95% CI] = 0.97 [0.68, 1.39]). On restricting the analysis to GLP-1RA, then to SGLT2i, results for AA patients remained non-significant. On comparing results for GLP-1RA to those with SGLT2i, there was no difference between the groups. We conclude that AA are not well represented in CVST. Because cardiovascular outcomes were not significantly improved for AA, it remains unclear whether GLP-1RA or SGLT2i would reduce cardiovascular risk in AA. Disclosure B.M. Mishriky: None. J.R. Powell: None. J.A. Wittwer: None. J.X. Chu: None. K. Sewell: None. Q. Wu: None. D.M. Cummings: None.

Clinical Features Associated with Survival Outcome in African-American Patients with Hepatocellular Carcinoma.

African-Americans (AA) have a higher incidence of hepatocellular carcinoma (HCC) and lower survival. We characterized survival rates and clinical features associated with survival in AA vs. Caucasians with HCC over the past two decades. HCC patients from three US medical centers were matched by year of diagnosis (1991-2016): AA (n = 578)/Caucasian (n = 578) and placed in one of two groups-HCC diagnosed prior to 2010 or 2010 and after. Data were obtained from chart review and the National Death Index. Multivariate and survival analysis controlling for key predictors were conducted. Prior to 2010, there was no difference in survival between Caucasians and AA (p = 0.61). After 2010, AA patients had poorer survival compared to Caucasians (35% vs. 44%, respectively, p = 0.044). Over time, survival improved for Caucasians (32% before 2010 vs. 44% after 2010, p = 0.003), but not AA (36% vs. 35%, p = 0.50). AA on presentation (in the after 2010 cohort) were more likely to have BCLC (Barcelona Clinic Liver Cancer) stage C (24% vs. 15%, p = 0.010) and less likely to receive treatment (85% vs. 93%, p = 0.002) compared to matched Caucasians. BCLC beyond stage A (aHR: 1.75, 95% CI: 1.26-2.43, p = 0.001) and child's class C (aHR 2.05, 95% CI: 1.23-3.41, p = 0.006) were the strongest predictors of mortality, while race was not. African-Americans presented with more advanced HCC and had poorer survival compared to Caucasians after 2010. Tumor stage was an independent predictor of mortality, but ethnicity was not. Further efforts are needed to improve early HCC diagnosis for AA.

Differences in Presentation and Survival Outcomes for African American Patients with Newly Diagnosed Multiple Myeloma

Background: Though the incidence of MM is two- to threefold higher in the African American (AA) population compared to Caucasians, reported long term outcomes are less favorable presumably due to inequities in access to healthcare. Little is known about the biology or disease presentation among AAs. We have conducted a retrospective analysis of our institutional data of 1000 patients treated with RVD induction therapy, specifically assessing differences in presentation, disease biology, and outcomes in AA patients.Methods: A total of 1000 newly diagnosed MM patients were treated with RVD induction therapy [R - 25 mg/day (days 1-14), V - 1.3 mg/m2 (days 1, 4 8, 11) and D - 40 mg once/twice weekly as tolerated every 21 days] from January 1st 2005 until August 31st 2016. Dose-adjustments were made based on the treating physician's discretion and patient tolerability. Demographic and outcomes data for the patients were obtained from our IRB approved myeloma database and responses were evaluated per IMWG Uniform Response Criteria.Results: Of the 1000 patients included in the analysis, 564 (56.4%) of patients were white (W), and 339 (33.9%) were AA, consistent with the demographic representation of the state of GA and our institutional referral population. Median age of this cohort was 61 years (range 16-83), 57 for AA patients (range, 24-83) compared to 62 (range, 16-81) in white patients, suggesting the onset is earlier among AA which has been previously reported in population based studies. Other notable characteristics include: 42.5%M/57.5% F for AA cohort and 61.7%M/38.3%F for white cohort. In regard to stage, AA: 73.9% stage I/II, 26.1% stage III; W: 77.1% stage I/II, 22.9% stage III, showing no difference in prognostic staging at presentation. There was no statistically significant difference in the presenting labs between AA and whites except for hemoglobin, with more AA patients presenting with Hgb≤9.9 g/dL (45.7% AA vs 32.5% W, p <.0001).In terms of prevalence of high-risk cytogenetics, there was no significant difference between the two cohorts in: complex karyotype 16% white/14.4% AA; t(14;16) 2.4% W/2.8% AA; t(4;14) 4.7% W/5.0% AA; t(11;14) 11.7% W/15.9% AA; or del1p 6.5%W/7.8%AA. However, there were significant differences found in the rates of: amp 1q 19.2% W/10.6% AA, (p<.0001), del13 28.3% W/19.6% AA (p=.003), and del17p 11.7% W/7.2% AA (p=.019), all three significantly less frequent in AAs.Median time to transplant for the entire cohort was 5 months (range, 1-124), and median time to best response was 3 months (range, 0-39). There was no significant difference in the number of patients who underwent ASCT (84% W vs 82% AA, p=.241), nor in ≥VGPR rates post-induction and 100 days post-ASCT: 69.9% W vs 64.5% AA (p=.056) and 88.1% W vs 86.7% in AA patients (p=.317), respectively.Median PFS for the entire cohort was 63 months, 62 months (54-69.9) for white patients versus 65 months (53-76.9) for AA patients (p=0.403). At a median follow up of 38 months, median OS has not yet been reached.Conclusions: This is the largest reported cohort of myeloma patients treated with RVD induction, with one-third of the patients representing the AA population. In our dataset, AAs are diagnosed 5 years younger, with lower hemoglobin at presentation and lower rates of amp1q, del13 and del17p when compared to whites. When offered the same induction regimen and opportunity for ASCT, AAs tend to experience the same survival benefits as their white counterparts. The lack of significant difference in PFS or OS suggests standardization and improved access to care could lead to better long-term outcomes in the AA population. DisclosuresHofmeister:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Adaptive biotechnologies: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees. Heffner:Genentech: Research Funding; Pharmacyclics: Research Funding; ADC Therapeutics: Research Funding; Kite Pharma: Research Funding. Boise:AstraZeneca: Honoraria; Abbvie: Consultancy. Kaufman:BMS: Consultancy; Janssen: Consultancy; Karyopharm: Other: data monitoring committee; Abbvie: Consultancy; Roche: Consultancy. Lonial:Amgen: Research Funding. Nooka:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Spectrum Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive technologies: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Clinical outcomes of African American patients with advanced or metastatic non-small cell lung cancer on Nivolumab in a single community-based cancer center.

African Americans (AA) have the highest incidence and mortality rates with lung cancer. They are diagnosed at an earlier age with more advanced disease. Programmed cell death protein-1 inhibitor, Nivolumab, was approved as a second-line agent after failure of platinum-based therapy for advanced or metastatic non-small cell lung cancer (NSCLC). The original studies leading to the approval of Nivolumab had insufficient AA patients, thus there is still inadequate knowledge on treatment outcomes among AA patients. Our primary study endpoints were to determine the median overall survival, 1-year overall survival rate, median progression-free survival, and 1-year progression-free survival rate of patients with advanced or metastatic non-small cell lung cancer on Nivolumab. Our secondary study endpoints were to determine the overall tumor response rate, median time to response, median duration of response, and incidence of treatment-related adverse events of grade 3 or 4. In this retrospective study, we reviewed the charts of 38 patients, 29 of which were AA, with advanced or metastatic NSCLC who received Nivolumab from March 1, 2015 until November 30, 2017 from a single community-based cancer center and compared our results with historical data. Adenocarcinoma was the most common histology (71%) among all patients. Seven (18%) continued to use Nivolumab while 21 (55%) discontinued the treatment mainly due to progression of the disease. The median overall survival was 21.4months (95% CI 13.5-27.4) and 17.6months (95% CI 11.5-27.6) for all the patients and AA, respectively. Both have statistically significant difference (P < 0.001) compared to the historical studies of Borghaei et al. and Brahmer et al. At 1 year, the overall survival rate was 73% (95% CI 50-86) and 66% (95% CI 40-82) for all patients and AA, respectively. The median progression-free survival was also statistically significant (P < 0.001) between all the patients 6.3months (95% CI 2.8-8), AA 6.0months (95% CI 2.3-8.0), and the said historical studies. The 1-year progression-free survival rate was 23% (95% CI 10-39) and 28% (95% CI 12-47) for all patients and AA, respectively. Overall tumor response rate which includes complete and partial responses was 21% (95% CI 10-37) and 24% (95% CI 10-43) for all patients and AA, respectively. The median time to response was 3 and 2.8months for all patients and AA, respectively. The median duration of response was 3.8 and 4.0months for all patients and AA, respectively. Treatment-related adverse events of grade 3 or 4 were reported in 8 and 10% in all patients and AA, respectively, similar to the rates previously shown. AA patients with advanced or metastatic NSCLC on Nivolumab had increased overall survival and progression-free survival with similar grade 3 or 4 treatment-related adverse events. Providing adequate access to immunotherapy is indispensable to maximize survival benefit for AA patients.

Clinical outcomes of African-American patients with advanced or metastatic non-small cell lung cancer on nivolumab in a single community based cancer center.

e21131Background: Lung cancer is the leading cause of cancer-related deaths in African-Americans (AA) with increased incidence and decreased survival rates in all stages of the disease. AA are diag...

MiRNA profiling in a case: Control study of African American women with uterine serous carcinoma (USC).

e17116 Background: USC is an aggressive subtype of endometrial cancer associated with worse outcomes in African American patients. We evaluated differences in tumor miRNA expression by race, clinical and tumor characteristics, and survival outcomes. Methods: FFPE tumor tissue from hysterectomy specimens was identified for 29 African American cases. Case matching was performed by computer-based random assignment in a 1:1 ratio with Caucasian controls based on age ( &lt; 70 vs. ≥70 years), stage (FIGO I/II vs. III/IV) and histologic subtype (pure vs. mixed). RNA was extracted from 77 specimens with sufficient tumor cellularity (54 tumors and 23 matched normal endometrium). miRNA array profiling was performed by microRNA Hi-Power Labeling (Hy3/Hy5) and hybridization to miRCURY LNA microRNA Array 7th Gen (Exiqon, Denmark). Analysis was performed with R/Bioconductor using a moderated t-statistic with multiple testing correction. Validation was done using the TCGA dataset. Results: Clinical and treatment characteristics were similar for cases and controls, although use of adjuvant radiation was less common in African Americans (p = 0.03). With a median follow-up of 43 months, 17 patients had recurrent or progressive disease. DFS and OS rates were similar by race (both logrank p &gt; 0.5). Of 968 miRNAs analyzed, 649 were differentially expressed in normal endometrium vs. tumor. When compared by race, histologic subtype, stage or presence of LVI, no differentially expressed miRNAs were identified. In patients with disease recurrence at 3 years, miR-223 was significantly upregulated (fold change 1.5; p = 0.002). In validation using a TCGA dataset of 131 patients with mixed (n = 22) or pure serous (n = 109) histology, increased miR-223 expression ( &gt; median) was associated with worse overall survival (HR 2.47; 95%CI 0.9-6.6). After adjustment for patient age and BMI, upregulation of miR-223 was a significant risk factor for death (adjusted HR 2.94; 95%CI 1.01-8.52). Conclusions: Upregulation of miR-223 was associated with disease recurrence in a cohort of women with uterine serous carcinoma and validated by TCGA data. miRNA profiling did not identify biological differences between African American and Caucasian patients.

Body Mass Index and Intensive Care Unit Outcomes in African American Patients.

We sought to determine whether body mass index (BMI) is associated with worse intensive care unit (ICU) outcomes among Black patients. Patients admitted to the medical ICU during 2012 were categorized into six BMI groups based on the World Health Organization criteria. ICU mortality, ICU and hospital length of stay (LOS), need for and duration of mechanical ventilation and organ failure rate were assessed. A total of 605 patients with mean age 58.9 ± 16.0 years were studied. Compared with those with normal BMI, obese patients had significant higher rates of hypertension, diabetes mellitus and obstructive sleep apnea diagnoses (P<.001 for all). A total of 100 (16.5%) patients died during their ICU stay. Obesity was not associated with increased odds of ICU mortality (OR=.58; 95% CI, .16-2.20). Moreover, improved survival was observed for class II obese patients (OR, .031; 95% CI, .001-.863). There were no differences in the need for and duration of mechanical ventilation between the BMI groups. However, ICU and hospital LOS were significantly longer in patients with obesity. Obesity was not associated with increased ICU mortality; however, obesity was associated with increased comorbid illness and with significant longer ICU and hospital length of stay.

Su1005 - Location of Healthcare Delivery (County vs Tertiary Care Based Centers) May Influence Disease Related Outcomes in African-American Patients with Inflammatory Bowel Disease (IBD)

Su1005 - Location of Healthcare Delivery (County vs Tertiary Care Based Centers) May Influence Disease Related Outcomes in African-American Patients with Inflammatory Bowel Disease (IBD)

Autologous Stem Cell Transplant Improves Depth of Response and Outcomes in African American Patients When Compared With Caucasian Patients

Autologous Stem Cell Transplant Improves Depth of Response and Outcomes in African American Patients When Compared With Caucasian Patients

Socioeconomic Status and ICU Outcomes in African-American Patients With Sepsis

Socioeconomic Status and ICU Outcomes in African-American Patients With Sepsis

Perioperative Outcomes of African-American Patients Undergoing Bariatric Surgery

Perioperative Outcomes of African-American Patients Undergoing Bariatric Surgery

Intrinsic Genomic Differences Between African American and White Patients With Clear Cell Renal Cell Carcinoma.

There are well-documented racial disparities in outcomes for African American patients with clear cell renal cell carcinoma (ccRCC). Despite a dramatic improvement in overall survival in white patients since the advent of targeted therapy, survival for African Americans with advanced ccRCC has not changed. There is little known about potential racial differences in tumor biology of ccRCC. To determine if there are racial differences in the somatic mutation rate and gene expression of ccRCC tumors from white and African American patients. Overall, 438 patients with ccRCC were identified through The Cancer Genome Atlas (TCGA) clear cell kidney (KIRC) dataset (419 white and 19 African American patients). The GSE25540 dataset containing 135 patients (125 white and 10 African American patients) was used for validation. Tumor samples were collected from numerous cancer centers and were examined for racial differences in somatic mutation rates and RNA expression. Racial differences in somatic mutation rates and RNA expression were examined. The comparison of somatic mutation rates and differences in RNA expression in white and African American patients with ccRCC. Overall, 419 ccRCC tumor data sets from non-Hispanic white patients and 19 from non-Hispanic African American patients were identified through the publically available TCGA KIRC data set, and a validation set of 125 white and 10 African American ccRCC patient tumors was identified from the publicly available GSE25540 data set. African American patients were significantly less likely than white patients to have VHL mutations (2 of 12 [17%] vs 175 of 351 [50%], respectively; P = .04) and were enriched in the ccB molecular subtype (79% in African American vs 45% in white patients ; P = .005), a molecular subtype that carries a worse prognosis. It was found that RNA expression analysis revealed relative down-regulation of hypoxia-inducible factor (HIF) and vascular endothelial growth factor (VEGF)-associated pathways in African American patients compared with white patients. African American patients have less frequent VHL inactivation, are enriched in the ccB molecular subtype, and have decreased up-regulation of HIF-associated gene signatures than white patients. These genomic differences would predict decreased responsiveness to VEGF-targeted therapy and are a biologically plausible contributing factor to the worse survival of African American patients with ccRCC, even in the targeted therapy era.

Abstract IA24: Lung cancer: Disparities and implications for immunotherapy

Abstract Lung cancer is diagnosed in nearly 225,000 patients each year in the United States. Majority of the patients present with advanced stage of the disease at the time of diagnosis. This is a major impediment to improving cure rates for patients with lung cancer. Lung cancer incidence rate is higher in African American (AA) patients compared to Caucasian patients. In addition, AA patients have certain important differences from Caucasian patients with lung cancer. They are more likely to be diagnosed at a younger age with lung cancer and also have a higher prevalence of smoking-related lung cancer. AA patients are more likely to present with poorer prognostic features, have advanced stage disease, and experience delays in receiving therapy. Consequently, the improved outcomes achieved with various novel therapeutic modalities in lung cancer have not fully benefitted the AA patient population. Systemic therapy is utilized for the treatment of nearly every stage of lung cancer. Platinum-based chemotherapy regimens have been used in all histological sub-types of lung cancer as cornerstone of therapy. In recent years, a greater understanding of molecular characteristics of lung cancer have led to the adoption of targeted therapies for certain patient subsets. Patients with an activating mutation in the epidermal growth factor receptor (EGFR) pathway are treated with specific tyrosine kinase inhibitors. Similarly, patients with the anaplastic lymphoma kinase gene rearrangement are treated with ALK inhibitors. The prevalence of EGFR mutation is variable based on racial background. Asian patients have higher mutation prevalence compared to Caucasian or AA patient population. We recently demonstrated that AA patients are less likely to harbor a driver mutation compared to Caucasian patients with lung adenocarcinoma. However, survival outcomes were similar for AA and Caucasian patients that were treated with a targeted agent for the specific mutation. Therefore, it is critical to conduct molecular testing in AA patients according to standard guidelines. In 2015, the US FDA approved nivolumab, an immune checkpoint inhibitor for the treatment of advanced squamous cell lung cancer. In a phase III study, Nivolumab demonstrated an improvement in response rate, progression-free survival and overall survival compared to docetaxel in patients with advanced squamous cell lung cancer that had progressed on prior therapy with a platinum-based regimen. Improved efficacy was also observed with nivolumab in non-squamous histology relative to docetaxel. Pembrolizumab, another checkpoint inhibitor, has received approval for the treatment of advanced NSCLC in patients with PDL-1 expressing tumors. The advent of immune checkpoint inhibitors has provided an entirely new therapeutic tool for lung cancer. While this class of agents benefit patients with lung cancer, the response rate is approximately 20%, suggesting that biomarkers are needed for proper patient selection. Recent studies have suggested a higher likelihood of response to immune checkpoint inhibitors in patients with a higher mutation burden. The burden of somatic mutations appears to be different in AA patients with lung cancer. This is likely to have an impact on outcomes with immune checkpoint inhibitors in AA patients. Access to this new class of agents is also likely to be influenced by socioeconomic status, which will have a bearing on AA patients. Taken together, it is important to study the outcomes of AA patients with immune checkpoint inhibitors and overcome potential barriers that could limit their ability to derive maximal clinical benefit. Citation Format: Suresh S. Ramalingam. Lung cancer: Disparities and implications for immunotherapy. [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 IA24.

Differences in Cell of Origin (COO) Affect Outcomes in Caucasian(C) but Not in African American(AA) Patients with Diffuse Large B-Cell Lymphoma(DLBCL)

Introduction: DLBCL is an aggressive mature B-cell neoplasm with a low incidence in African Americans and other minority groups. The differences in outcomes based on DLBCL Cell of Origin(COO) immunophenotypic subtypes as defined by the Hans algorithm using CD10, Bcl-6, and MUM1 namely germinal center B-cell (GCB) and non-GCB have been based on predominantly Caucasian patients (pts) and their impact on outcomes in AA patients have not been well studied.Material and Methods: A retrospective review of clinicopathologic data from patients diagnosed and treated for DLBCL at UAB between 2002-2011 was conducted following IRB approval .The data collected included patient demographics (age, sex, self identified race), DLBCL subtype (GCB vs. non-GCB based on the Hans algorithm), disease stage, first line therapy regimens and patient outcomes. We analyzed group differences in both C and AA pts with GCB and non-GCB subtypes of DLBCL in all the parameters mentioned above using the chi square test for categorical variables,. In addition, OS was examined using Kaplan Meier curves and the log rank test. We performed univariate and multivariate analyses to examine the effects of variables of interest on OS. All results were considered statistically significant at α=0.05 level.Results: We included a total of 259 pts in our analysis after excluding patients with missing demographics, disease related data, primary mediastianal DLBCL, missing first line therapy data and outcomes data as well as race identified as other than C or AA. 45 patients (17.4%) of patients self identified as AA and 214 (82.6%) self identified as Caucasian. The mean age of presentation for AA pts was 52 yrs compared to 58 years for C patients (p=0.045) and 28 (62.2%) AA patients presented with advanced Stage III and IV disease compared to 89 (44.6%) of C patients (P=0.04) both being statistically significant. Based on COO characterization using immunophenotype by Hans algorithm, 27 AA pts (60%) and 145(67%) of C pts were GCB by immunophenotype(p=0.317). 95% of all patients received R-CHOP as first line therapy , 3.5% received R-CVP and the remaining received a combination of Rituximab alone, FCR or radiation therapy .On analyzing OS based on COO, AA patients did not demonstrate a significant difference in OS based on COO with both GCB and non-GCB groups having a median OS of 84 months ( p=0.74)( 95% CI 72-121 months). However, the median OS for C pts with GCB phenotype was 104 months compared to 25 months for the non-GCB phenotype and the median OS was 55 months +/-12.6 months for the C pt group as a whole( p<0.001 by log rank test )which was highly statistically significant.Multivariate analyses of different factors affecting OS showed only COO (p<0.001), age(p=0.07) and stage of DLBCL at presentation(p=0.027) to affect OS significantly.Race,Gender and IPI score did not appear to impact OS significantly.Conclusion: Our study aimed to study the impact of COO and Race on OS in DLBCL especially in AA pts where this has not been well characterized. Our results show that as expected the incidence of DLBCL is lower in AA patients compared to C pts. However, DLBCL presents at younger age and with more advanced stage in AA than in C patients. Although distribution of COO is similar in AA and C patients, our findings suggest that COO may not have the same effect on prognosis among AA pts as it does among the C pt population where we see non-GCB patients do significantly worse than their GCB counterparts. This may reflect a different disease biology in AA patients that has yet to be understood. Our study limitations include not taking into account disease relapse, second line therapy and effect of autologous bone marrow transplantation on overall survival. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.