Shreders, Amanda

Abstract Introduction Immune thrombocytopenia (ITP) is an acquired disorder characterized by immune-mediated platelet destruction along with decreased platelet production. Adults with ITP are treated initially with glucocorticoids, intravenous immunoglobulin, and/or anti-D, but as many as 80% of patients (pts) will eventually relapse and become steroid-refractory. There is no universally agreed upon 2nd line therapy for ITP and consensus guidelines recommend either rituximab (R) or splenectomy (S) as acceptable, potentially curative options. Long-term responses to 2nd line S have been reported around 60%, and around 25% for R. It is unknown whether long-term outcome in the 3rd line setting is influenced by sequence of therapy. We evaluated the impact of sequence of 2nd and 3rdline therapy with R and/or S. Methods We identified all pts with ITP treated from 1990 through 2015 at the three Mayo Clinic (Arizona, Florida, and Minnesota) sites that were treated with R and/or S. Patients were excluded who were <18 years of age at the time of second-line treatment. Those with secondary ITP that received specific treatment for an infectious, autoimmune, or malignant condition causing thrombocytopenia were excluded. Patients with Evan's syndrome were included if the treatment was for thrombocytopenia, and not primarily for hemolytic anemia. For this analysis, secondary ITP was defined as ITP associated with hematologic malignancy. Hematologic malignancies did not require specific therapy at the time of treatment for ITP. Patients with uncontrolled infections or uncontrolled autoimmune disorders were excluded from analysis. We collected data from medical records regarding demographics, medical history, treatment history, response to treatment, and relapse. Medical history was captured for all concurrent diagnoses that could be considered associated with ITP including infectious and autoimmune conditions. Primary end-points were freedom from relapse after 2nd and 3rd line treatment with R or S. We used Kaplan-Meier method to estimate freedom from relapse after 2nd and 3rd line treatments. We also evaluated response to treatment, as defined by a platelet count >30,000/mm3 according to consensus guidelines. We performed three separate analyses for the entire cohort, primary ITP, and secondary ITP (separating out those with a concurrent diagnosis of malignancy). Results We identified 222 patients with a diagnosis of ITP, of which 191 had primary and 31 had secondary ITP. Treatment characteristics were similar in all groups except that pts treated initially with S were younger at diagnosis than pts treated with R (49 vs 60 years, P=0.003) and at time of 2ndline treatment (51.5 vs 61 years, P=0.018). For the overall cohort, patients treated with S as second-line therapy were more likely to achieve CR (86.6% vs 44%, P<0.0001), and had a significantly higher freedom from relapse at 5y (53.57% v. 14.96%, P<0.0001). Patients treated with S followed by R (S to R) had a trend towards higher 2y freedom from relapse than those treated with R followed by S (R to S) (69.48% v. 58.43%, P=0.3264). These data remained similar when primary ITP and secondary ITP were separated (data not shown). Conclusions These data support that S provides superior FFR at 5 years compared to R as second line treatment and suggests that, when needed, splenectomy followed by rituximab as opposed to rituximab followed by splenectomy might have a slight advantage. Disclosures No relevant conflicts of interest to declare.

Abstract Background: Large case-control studies have identified common epidemiologic exposures associated with risk of AML development, including obesity [BMI ≥30 kg/m2] associated with 2-fold increase risk. However it is not known whether individual risk factors are associated with unique AML genetic lesions. We have recently identified a significant association of some common exposures including obesity with unique disease cytogenetic subgroups in a cohort of n=295 consecutive AML patients diagnosed and treated at Mayo Clinic [Cancer Epidemiol 39:1084, 2015]. Aberrant DNA methylation is a hallmark of cancer and has been reported in AML, and we therefore performed an analysis of global DNA methylation in patients in this cohort to determine whether specific epidemiologic exposures are associated with a unique pattern of DNA methylation. Methods: Patients in the initial cohort were previously reported. An available baseline AML bone marrow cytogenetic pellet from diagnosis was identified for n=148 patients (50.2%). Following IRB approval and using previously reported techniques [Leukemia 24:1283, 2010], leukemia DNA was isolated from the remnant diagnostic cytogenetic samples and processed on the HumanMethylation450 BeadChip array (Illumina). Individual CpG dinucleotides were assigned a Beta value (i.e. methylation value) ranging from 0 (unmethylated) to 1 (methylated). We excluded those with minor methylation changes (<0.2 between any two samples), resulting in 383,524 CpG's. For the purposes of this first analysis we have focused only on CpG's with an inter-quartile range (IQR, i.e. difference between 75th and 25th percentiles) of greater than 0.25, comprising a total of 39,657 CpG's. An unsupervised cluster analysis of differential methylation was generated ("Heatmap", Figure). Univariate and multivariable analyses were performed adjusting for age as a continuous variable to determine the association of individual exposures with unique methylation clusters (primary endpoint), and we also evaluated the association of clinical characteristics and clinical outcomes after therapy (secondary endpoint). The median age of patients was 69 yrs (range 19-89), male 65%, and Caucasian 89%. The median BMI was 27.2 (range 16.9-59.9), and n=47 patients (32%) had BMI ≥30. Standard cytogenetic risk groups were applied [favorable (n=8), normal (n=61), intermediate abnormal (n=32) and poor (n=47)]. Results: We identified 4 distinct methylation clusters (Figure: Cluster #1, Black horizontal bar; Cluster #2, Green; Cluster #3, Blue; and Cluster #4, Red). Multivariate analysis of select variables is shown in Table. Patients in cluster #1 were significantly more likely to have a BMI ≥30 [Odds Ratio (OR) 2.49, p=0.017] and more likely to have favorable risk cytogenetics although this was not statistically significant [OR 6.71, p=0.088], while those in cluster #2 were significantly more likely to be have a history of regular NSAID use [OR 3.26, p=0.03] and less likely to have normal [OR 0.40, p=0.044] and possibly intermediate abnormal cytogenetics [OR 0.34, p=0.051]. Those in cluster #3 were significantly younger [median age 48 yrs, p<0.001] and were also more likely to have prior history MDS although this was not statistically significant [OR 3.7, p=0.082]. Cluster #4 was not correlated with any distinct exposure apart from possible decreased alcohol use [OR 0.3, p=0.079]. History of past or current tobacco use, regular acetaminophen use, documented myelotoxin exposure, family history, and secondary AML did not correlate with a unique methylation cluster. There was no independent association of methylation cluster with overall survival (p=0.46), although among patients receiving intensive therapy cluster #2 was associated with lower complete remission rate [OR 0.28 (95% CI 0.09-0.86), p=0.026]. Conclusion: This first analysis of AML molecular epidemiology and clinical outcome suggests that specific disease risk factors (esp. obesity and age) are associated with unique leukemia DNA methylation clusters. In addition, aberrant methylation is associated with some clinical features and with outcome after therapy, suggesting that epidemiologic risk factors may have a prognostic impact. This provides novel insight into leukemogenesis, and will guide prospective studies of AML epidemiology and outcome. Figure. Figure. Disclosures Foran: medscape: Honoraria; pfizer: Honoraria; Millennium Pharmaceuticals, Inc.: Research Funding; novartis: Honoraria; karyopharm: Honoraria; boehringer ingelheim: Research Funding; agios: Research Funding; Cellerant: Research Funding.

Abstract Background WM remains an incurable cancer despite recent advances. While a phase II trial has demonstrated efficacy of dexamethasone, rituximab and cyclophosphamide (DRC) in the treatment-naïve (TN) patients, this regimen has not been studied systematically in the relapsed/refractory (R/R) setting. Recent data has suggested the MYD88mutation status in WM patients can serve as a predictive marker with therapies such as ibrutinib. We examined the efficacy and tolerability of up to 6 cycles of DRC, with focus on R/R population and activity of this regimen with respect to the patients' MYD88L265Pstatus. Methods Records of WM patients seen consecutively at Mayo Clinic campuses in Rochester, Arizona and Florida from 01/2007 to 12/2014 were reviewed. MYD88L265P status, as assessed by AS-PCR, was recorded when available. Data obtained from symptomatic patients treated with DRC (dexamethasone 20 mg intravenously followed by rituximab 375 mg/m2 intravenously on day 1 and cyclophosphamide 100 mg/m2 orally bid on days 1 to 5) were analyzed. Time-to-event analyses were performed from DRC therapy using the Kaplan-Meier method. We used the Consensus response criteria (6th International Workshop). Results Of 100 symptomatic patients who received DRC, 50 had R/R WM (40% refractory) and 50 were TN. Table 1 shows the patients' baseline characteristics. In the R/R population, DRC was 2nd line (range 2-8) therapy in 58% of patients. The median IgM levels declined from 3,870 mg/dL to 1,846 mg/dL (p=0.0001) at best response. Median follow-up from DRC was 51 months (95% CI: 38-55). The median time-to-best response was 6.8 (0.5-28) months. Overall response rate (ORR) was 87% [VGPR 4%, PR 64%, MR 19%]. Four patients (9%) achieved SD and 2 patients (4%) had PD. Of the sixteen deaths (32%) noted at time of analysis, 11 were related to progressive disease. The median disease-specific survival (DSS) from DRC was not reached (NR) (95% CI: NR-NR). The median progression-free survival (PFS) and time-to-next-therapy (TTNT) were 32 months (95% CI: 15-51) and 50 months (95% CI: 35-60), respectively. In contrast, in the TN patients the median IgM levels declined from 4,130 mg/dL to 1,250 mg/dL (p=0.0001) at best response; median time to best response was 11 (0.6-47) months; median follow-up from DRC was 30 months (95% CI: 21-36). ORR was 96% [VGPR 17% (n=8), PR 70% (n=32), MR 9% (n=4)]. Of the 7 deaths (14%) at time of analysis, 4 were related to WM progression. Median DSS from DRC was NR (95% CI: NR-NR); median PFS and TTNT were 34 months (95% CI: 23-NR) and NR (95% CI: 37-NR), respectively. Among 29 genotyped patients in whom MYD88 mutation status was available, MYD88L265P was present in 25 patients (8 of 10 TN and 17 of 19 R/R patients). The response rates and the time-to-event outcomes were similar in the MYD88L265P and wild-type patients. Grade ≥3 adverse effects included neutropenia (20%), thrombocytopenia (7%) and infections (3%). Conclusions Similar to the frontline setting, DRC is an active and well-tolerated salvage regimen. In contrast to ibrutinib, DRC offers a less expensive, limited-duration treatment option, with preliminary data suggesting activity independent of patients' MYD88 mutation status. Disclosures Ailawadhi: Pharmacyclics: Consultancy; Novartis: Consultancy; Amgen Inc: Consultancy; Takeda Oncology: Consultancy. Kumar:Glycomimetics: Consultancy; Sanofi: Consultancy, Research Funding; Noxxon Pharma: Consultancy, Research Funding; Onyx: Consultancy, Research Funding; AbbVie: Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Kesios: Consultancy; Array BioPharma: Consultancy, Research Funding; Skyline: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy. Dispenzieri:Jannsen: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; pfizer: Research Funding; Celgene: Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees; Alnylam: Research Funding; GSK: Membership on an entity's Board of Directors or advisory committees. Ansell:BMS, Seattle Genetics, Merck, Celldex and Affimed: Research Funding. Kapoor:Amgen: Research Funding; Celgene: Research Funding; Takeda: Research Funding.

Abstract Background Bendamustine/rituximab (BR) and dexamethasone/rituximab/cyclophosphamide (DRC) combination therapy are acceptable options for the treatment of WM, both in the frontline or salvage setting. Prospective data, however, are only available in treatment-naïve (TN) WM patients, and no direct comparison between BR and DRC has been reported. We compared outcomes of BR and DRC in relapsed/refractory (R/R) and TN WM patients seen at a single institution. Methods Records of WM patients seen consecutively at Mayo Clinic from 01/2007 to 12/2014 were reviewed. The MYD88L265P status, as assessed by AS-PCR, was recorded when available. The data obtained from symptomatic patients treated with DRC or BR were analyzed. The time-to-event analyses were performed from DRC or BR therapy using the Kaplan-Meier method. We used the Consensus criteria (6th International Workshop) for response assessment. Results Of 160 WM patients, 60 patients received BR (73% in R/R setting) and 100 patients received DRC (50% in R/R setting). In the R/R population, BR was the 2nd line (range 2-11) therapy in 47% of patients, while DRC was 2nd line (range 2-8) in 58% of patients. Rituximab monotherapy was the only prior line of therapy in 8 (20%) patients in the BR group and 20 (40%) in the DRC group (p=0.66). Baseline characteristics were similar in patients treated with BR or DRC (Table 1). Six patients received both BR and DRC during their disease course and overlapped between the 2 cohorts. Among the previous untreated patients, the median IgM levels decreased from 3,785 mg/dL to 724 mg/dL (p=0.0001) at best response with BR, while it decreased from 4,130 mg/dL to 1,250 mg/dL (p=0.001) with DRC. The median time to best response was 6.1 (1-25) months in the BR group and 11 (0.5-47) months in the DRC group (p=0.13). For patients treated with BR, the overall response rate (ORR) was 93% [VGPR 29% (n=4), PR 57% (n=8), MR 7% (n=1)]. One patient (7%) had progressive disease. For patients treated with DRC, ORR was 96% [VGPR 17% (n=8), PR 70% (n=32), MR 9% (n=4)]. One patient (4%) achieved SD. Median follow up in the BR and DRC groups were similar (30 months). The 2-year progression-free survival (PFS) was 88% and 61% in the BR and DRC groups, respectively (p=0.08). The 2-year time-to-next therapy (TTNT) was 88% and 76% in the BR and DRC groups, respectively (p=0.35). Median PFS, TTNT and disease specific survival (DSS) were not reached with either regimen. In the R/R setting, the median IgM levels decreased from 3,880 mg/dL to 659 mg/dL (p=0.0001) at best response with BR, and from 3,870 mg/dL to 1,846 mg/dL (p=0.001) with DRC. The median time to best response was similar [7 (1-39) months with BR and 7 (0.5-28) months with DRC (p=0.77)]. For patients treated with BR, ORR was 95% [CR 3% (n=1), VGPR 38% (n=14), PR 41% (n=15), MR 13% (n=5)]. Two patients (5%) had progressive disease. With DRC, the ORR was 87% [VGPR 4% (n=2), PR 64% (n=30), MR 19% (n=9)]. Four patients (9%) achieved SD and 2 patients (4%) had progressive disease. Median follow up from BR was 32 months and 51 months from DRC (p=0.24). The 2-year PFS was 66% and 53% in the BR and DRC groups, respectively (p=0.08). The 2-year TTNT was 75% and 68% in the BR and DRC groups, respectively (p=0.24). The median DSS in the BR group was 69 months (95% CI: 65-69) and NR (95% CI: NR-NR) in the DRC group (p=0.57). The proportion of patients with R/R disease was significantly higher in the BR cohort (Table 1). In a bivariate analysis of the entire cohort for PFS, incorporating the setting (TN vs. RR) and the regimen involved (BR vs. DRC), the latter emerged as a significant factor (hazard ratio 0.52, p=0.019) in favor of BR. Time-to-event outcomes and response rates were similar in the MYD88L265P and MYD88WT patients. Grade ≥ 3 adverse events were neutropenia (12%), infections (7%) and nausea/vomiting (2%) with BR, and neutropenia (20%), thrombocytopenia (7%) and infections (3%) with DRC. Conclusions Although both DRC and BR regimens show activity and comparable toxicities, BR regimen shows a trend for superior PFS in WM patients, both in the TN and R/R setting. No difference was seen in TTNT. MYD88 L265P mutation status does not appear to impact activity of BR or DRC. Randomized controlled trial(s) are needed to confirm our findings. Disclosures Ailawadhi: Pharmacyclics: Consultancy; Novartis: Consultancy; Amgen Inc: Consultancy; Takeda Oncology: Consultancy. Ansell:BMS, Seattle Genetics, Merck, Celldex and Affimed: Research Funding. Reeder:Millennium: Research Funding; BMS: Research Funding; Novartis: Research Funding; Celgene: Research Funding. Dispenzieri:Jannsen: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; pfizer: Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Alnylam: Research Funding; GSK: Membership on an entity's Board of Directors or advisory committees. Kumar:Sanofi: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; AbbVie: Research Funding; Array BioPharma: Consultancy, Research Funding; BMS: Consultancy; Kesios: Consultancy; Glycomimetics: Consultancy; Skyline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Noxxon Pharma: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Onyx: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. Kapoor:Celgene: Research Funding; Takeda: Research Funding; Amgen: Research Funding.

Abstract Background: Dexamethasone (dex) is an integral part of various anti-myeloma regimens both in the frontline and relapsed/refractory (RR) setting. Several clinical trials have shown that dex adds to the efficacy of novel therapeutic agents for multiple myeloma (MM). Yet, a substantial number of patients are intolerant to even the standard of care low-dose dex (40 mg weekly), especially in heavily pre-treated RRMM, possibly due to cumulative steroid toxicities and thus, require dex dose adjustments. There is a concern of compromising the efficacy of anti-MM regimens by adjusting the dex dose lower. We describe the frequency of dex dose adjustment, characteristics of patients who required it and its effect on patient outcomes in a large prospective clinical trial of pomalidomide (pom) and dex in RRMM (MC0789). Methods: We utilized data from the Pom-dex trial (MC0789), which treated RRMM patients in different cohorts of pom (2 vs. 4 mg; 21 vs 28 days cycle) with fixed dose dex (40 mg orally weekly). Patients were divided into 2 subgroups, with any dose adjustment/elimination of dex vs. not. Continuous and categorical variables were compared between the two groups using two-sample t-test/Wilcoxon rank sum test or Chi-squared test, respectively. Logistic regression and Cox regression models were used to find the univariate and stepwise multivariate predictors of response to treatment and overall mortality, respectively. Kaplan-Meier method was used to estimate overall survival (OS) at 1, 3, and 5 years. All statistical tests were two-sided with the alpha level set at 0.05 for statistical significance. Results: Results from the MC0789 clinical trial have been reported previously. Almost half of all treated patients in this trial had dex dose adjusted (n=175/343; 51%). The median number of cycles for the first dose adjustment in this group was 3 (range 1-62), with 46.5% of patients (n=82) having multiple dose adjustments and majority (58.3%, n=102) within the first 3 cycles of treatment. Patients in the dose adjustment group were significantly older (mean 65 vs 60 years; p=0.0001). Males, Whites and patients diagnosed before 2006 or with normal cytogenetics also had a higher incidence of dex dose adjustment, though this was not statistically significant. Patients with dex dose adjustment had a longer duration of treatment (mean 339 days) as compared to the non-adjusted cohort (mean 123.65 days) (95% CI 160.13, 270.58; p <0.0001). Dex dose adjustment was associated with a higher probability of responding in the clinical trial after a univariate (p<0.001) as well as multivariate (p<0.001) analysis. Patients with dex dose adjustment also had a significantly better OS at 1, 3 and 5 years by univariate (p<0.001) and multivariate (p<0.001) analysis. (Figure 1) The only other significant factor was lesser number of prior regimens (3 or less), associated with a higher probability of response (p=0.002) and survival (p<0.001). Conclusion: Our analysis established that in these heavily pre-treated RRMM patients, appropriate dose adjustment of dex did not compromise their response rates; patients remained on treatment significantly longer and had an improved survival. Majority of patients (58.3%) requiring dex dose adjustment had it instituted early during treatment (<3 cycles), suggesting that early disease progression was less likely to determine dex dose continuation or adjustment. Appropriate dex adjustments should be judiciously employed as they may ensure longer treatment duration with novel anti-MM therapeutic agents, conferring superior response and survival in this difficult to treat MM subgroup. This also paves the path to further optimize dex dose in various anti-MM regimens, especially in these patients who are more likely to be intolerant to it. Disclosures Kumar: Skyline, Noxxon: Honoraria; Celgene, Millennium, Onyx, Janssen, Noxxon, Sanofi, BMS, Skyline: Consultancy; Celgene, Millennium, Onyx, Novartis, Janssen, Sanofi: Research Funding.

Abstract Objective: Allogeneic stem cell transplant (ASCT) is a potentially curative treatment for many hematologic malignancies. HLA match is the principal factor in donor selection but the total antigenic landscape as seen by the donor immune cells extends beyond the HLA and minor HLA antigens. Thus, despite "perfect" HLA match graft versus host disease (GVHD) caused by alloreactive donor immune cells reacting to disparate antigens in the recipient, remains a significant cause of morbidity and mortality. Whole exome sequencing (WES) which assays all the protein coding nucleotide sequences provides a powerful means to assess the entire antigenic makeup of the individual. We examined the WES of sibling donor-recipient pairs undergoing BMT to assess the influence of the extent of genetic disparity and specific gene polymorphisms on GVHD. Methods: Sixteen matched sibling donor-recipient pairs receiving allogeneic stem cell transplants between June 2008 and April 2013 had samples available for retrospective WES. Transplant data including conditioning regimen, age of donor and recipient at the time of transplant, development and type of GVHD and cause of death were recorded. The sequencing was performed using Illumina HiSeq2000 and the single nucleotide variants (SNVs) and small insertions and deletions (INDELs) were identified using the haplotype caller within the Genome Analysis Toolkit GATK v2.7. Functional variants including non-synonymous, frame-shift, truncating, and splice site SNVs and INDELs identified were compared between donor and recipient and among those with GVHD and those without GVHD (non-GVHD). One-sided Fisher's exact test was used to determine the statistical significance of the SNPs in GVHD and non-GVHD. Candidate genes with a p value of <0.05 were further evaluated for their biochemical pathway and possible role in inflammatory or immune responses. Results: Nine of 16 patients had a diagnosis of AML or high grade myelodysplastic syndrome, 3 had a diagnosis of non- Hodgkin lymphoma, 1 had Hodgkin lymphoma, 1 had multiple myeloma, and 2 had CML. Six patients were conditioned with a myeloablative regimen, others with a reduced intensity conditioning regimen. Eight of 16 patients were female and 7 of 16 donors were female. Nine of 16 patients developed stage II-IV acute and/or chronic GVHD with 7 of them developing GVHD of the skin. A total of 12,623 genes with 43,670 functional variants were identified using WES. 134 genes had a p value < 0.05 and enrichment analysis was performed on these genes. 12 out of 134 genes were associated with gene ontology (GO) term "immune system development" with an unadjusted enrichment p-value 0.0015. Three (IL31RA, OSMR, SIRPA) out of 134 genes were associated with "inflammation_Jak-STAT pathway" with an adjusted enrichment p-value 0.07. Variants of IL31RA, OSMR, and PTX3 were identified as genes with polymorphisms associated with GVHD (p= 0.003, 0.01, and 0.01, respectively) with 5 variants identified in IL31RA, 7 variants in OSMR, and 2 variants in PTX3. Further investigation of these three genes revealed their role in inflammatory or immune responses. Discussion: GVHD is a cytokine mediated immune-inflammatory process that can occur despite "perfect" HLA matching. WES identified the extensive genetic variability between donors and recipients implying large allo-reactivity potential that can lead to GVHD. Quantification of genetic variation may allow for more precise determination of GVHD risk and better selection of donors. In our cohort, WES identified polymorphisms in IL31RA, OSMR, and PTX3 as statistically significantly associated with development of GVHD. The protein products of these three genes have each been shown to be involved in inflammatory processes and are influenced by other cytokines. IL31RA and OSMR are found in many tissues including the skin and lungs. They function both independently and as a heterodimer receptor capable of binding multiple cytokines including IL-31, IL-6, and TNF-α. PTX3 is a reactive protein that increases in response to cytokine release related to systemic inflammation. Levels of this protein have been used as a prognostic marker in many disease processes with high levels correlating with poor outcomes. The small sample size of our cohort precludes any firm conclusions but provides promising hypotheses for further evaluation in larger studies. Disclosures No relevant conflicts of interest to declare.

Abstract Background: Cancer diagnosis and treatment are important risk factors for developing clinical depression. Validated tools for screening distress and depression, such as Cancer Distress Thermometer (DT) and PHQ9 (Patient Health Questionnaire), are underutilized, despite endorsement by NCCN and Institute of Medicine. We investigated patient and treatment characteristics as well as patient endorsement of depression or anhedonia to predict those at risk of having depression. Methods: The PHQ9 and/or DT were administered prospectively to patients with hematologic malignancies (HM) before they started antineoplastic therapy at Mayo Clinic in Florida. Patient endorsement of depression or anhedonia was collected from the current visit information survey. Patient demographics, disease and treatment characteristics, chronic medication burden, Charlson comorbidity index, living situation, clinic/hospital visit burden in the month prior to screening and number of psychiatric medications for every patient were recorded. Intergroup comparison of categorical and continuous variables was done by Chi-square and Wilcoxon rank-sum tests, respectively. Linear or logistic regression models were used to compare PHQ9 score with DT (continuous) or endorsing depression or anhedonia (categorical) respectively. Multivariate models were constructed using the stepwise selection technique using all potential variables in the models. All analyses were completed using SAS v9.3. Results: Final analysis included 246 patients with a median age at diagnosis 64.5 (range: 18-94) years, diagnosed between 6/30/93-10/9/14 and screened between 1/13/11-2/13/15. PHQ9 score of ≥9 and DT score ≥5 suggested a high risk of depression and distress, respectively, as per published literature. Patient characteristics at time of survey and analysis are noted in table 1. PHQ9, DT and answers to two questions about depression and anhedonia were available on 129, 129 and 246 patients, respectively. 63% of patients were chemotherapy naïve. In multivariate analysis, PHQ9 score ≥9 was associated with living alone (p=0.003) (Fig.1a) and non-White race (p=0.043) (Fig.1b), while a DT score ≥5 was associated with being currently married (p=0.048) and female gender (p=0.02). The only characteristic significant on univariate but not on multivariate analysis being chemotherapy naive, associated with a DT score ≥5 (p=0.049). Answering "no" to both the questions regarding depression or anhedonia was significantly associated with a low score on PHQ9 (p=0.007). Age at diagnosis, Charlson comorbidity score, chronic medication or visit burden, daily psychiatric medication use or type of malignancy were not associated with scores on any screen. Conclusions: Causes of depression in patients with HM have not been fully explored. We validated previously known risk factors for depression, such as living alone. We also reported for the first time that non-White race independently predicts depression in these patients. Female patients and those currently married are at a higher risk of psychological distress, possibly due to fear of abandoning family. We also found that simply asking a patient two questions about feelings of depression or anhedonia significantly correlates with the well-established PHQ9. Our analysis provides simple tools and reveals at-risk patient subgroups with HM where depression and distress screening should be aggressively instituted for better resource utilization and survivorship. Table 1. Patient Characteristic N % Gender Male Female 146 100 59.4 40.6 Race White Non-White 216 30 87.8 12.2 Marital Status Married Not married* 180 66 73.2 26.8 Living Situation Alone With others 37 209 15 85 Type of Malignancy Aggressive lymphoid Indolent lymphoid Aggressive myeloid Indolent myeloid 124 94 25 3 50.4 38.2 10.2 1.2 Prior Cancer Treatment Yes No 91 155 37 63 Daily Psych Meds Yes No 52 194 21.1 78.9 Patient Status Alive Dead 191 55 77.6 22.4 *Not currently married=single, divorced, widowed or unknown Disclosures No relevant conflicts of interest to declare.

Abstract Background Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening systemic inflammatory condition. Due to rarity of the cases, it presents difficulties in diagnosis and management. Survival remains poor despite aggressive chemotherapy. Objective Patient outcomes varied markedly despite standardize therapy. Reliable prognostic disease markers may help to tailor intensity of therapy and predict long term outcomes. We attempt to look for variables associated with difference in mortality within 30 days of diagnosis. Methods We performed a retrospective search on mayo clinic patient database for the patients with the diagnosis of HLH from 2005 to 2015. HLH-04 criteria were used to select the study population. Patients were divided in two groups based on survival after the diagnosis. We analyzed different clinical and laboratory parameters to detect difference between the patients expired within 30 days of diagnosis and who survived longer than 30 days. Baseline Characteristics: Demographics: 40 patients were included in the analysis who met HLH- 04 criteria. Mean age was 49 years, 40% (16/40) were female and 60% (24/40) were male. Underlying HLH etiology was malignancy 37% (15/40), infection 20% (8/40), rheumatological 17% (7/40), idiopathic 20% (8/40). Two patients were peripartum and one with Kikuchi syndrome. EBV DNA PCR were positive in 32% (13/40) of patients. Table 1 show clinical and laboratory characteristics according to HLH-04 criteria. Treatment: Steroids were used in 92% (37/40), etoposide was used in 55% (22/40), and HLH 04 protocol (Etoposide/dexamethasone/cyclosporine) was used in 40% (16/40) of the patients. IVIG was used in 13% with underlying rheumatological process. Mean follow up was 57 weeks (0.1 to 336 weeks) for the whole group. Total 40% (16/40) died within 30 days of diagnosis. Results Risk of 30-days mortality was significantly higher in the patients with ferritin >5000 mcg/L at the time of diagnosis and age > 55 years. Out of total 40 patients, 54% (12/22) died in ferritin >5000mcg/L group and 22% (4/18) died in ferritin < 5000 mcg/L group within 30 days. (p-0.03) Death rate within 30 days was 65% (11/17) with age > 55 years and 22% (5/23) with age < 55 years at the time of diagnosis of HLH. (p-0.05) No difference between the groups in terms of gender, EBV positivity, underlying etiology and etoposide use was found in 30 days mortality. Table 2 summarizes the findings. Discussion HLH is a complex disorder with significant heterogeneity in terms of underlying etiology and response to treatments. Diagnosis is based on a set of clinical and investigational parameters. Most commonly used criteria are HLH-04. Treatment involves rapid immunosuppression with steroids, chemotherapy and calcineurin inhibitors. Previous retrospective studies have pointed out different risk factors associated with poor survival, which are malignancy, hypoalbuminemia, elevated creatinine and bilirubin. Ours is a relatively small retrospective analysis, but it shows significant prognostic value to elevated ferritin (>5000 mcg/L) at the time of diagnosis and age > 55 years. Survival remains poor in high risk patients despite aggressive therapy. Biological agents (IL1 and IL6 blockage) may provide new realm of therapy with tolerable toxicity profile. Conclusion Elevated ferritin at the time of diagnosis and older age are associated with significant risk of 30 day mortality in HLH. These factors can be incorporated in future clinical trials to choose different treatment pathways. Table. Clinical and laboratory characteristics according to HLH- 04 criteria Clinical/laboratory manifestation Presence of HLH 04 criteria (%) Fever > 38.5C 36/40 90 Splenomegaly 30/40 75 Hemoglobin < 9g/dl 22/40 55 ANC < 1000/microL 14/40 35 Platelets < 100, 000/microL 31/40 77 Triglyceride > 265 mg/dl 22/40 55 Ferritin > 500 mcg/L 36/40 90 Fibrinogen <150 mg/dl 12/38 31 sIL2- R > 1000u/ml 13/14 92 Low NK - cell activity 13/15 86 Presence of hemophagocytosis 33/39 84 Table 2. Difference in clinical variables based on survival after the diagnosis of HLH Survival < 30 days Survival > 30 days P value Age (years) 62 40 0.0004 Median time to start treatment (weeks) 40.7 8.6 0.23 Baseline ferritin (mcg/L) 32866 10667 0.01 Peak ferritin (mcg/L) 45870 29894 0.26 Albumin (g/dL) 2.3 2.6 0.41 LDH (U/L) 1271 720 0.51 Bilirubin (mg/dL) 8.9 4.5 0.14 Triglyceride (mg/dl) 260 276 0.70 Disclosures No relevant conflicts of interest to declare.

9525 Background: Historically, patients with advanced malignant melanoma had a dismal prognosis with an estimated median overall survival of nine months. Therapy response rates and long-term survival have significantly improved with the advent of immunotherapies and targeted chemotherapies. First approved in 2011, there has been subsequent development of more advanced immunotherapeutic agents and targeted chemotherapies, with continued improvement in median overall survival. We examined patterns in the use of immunotherapy and other systemic therapies for metastatic melanoma, as well as the demographic and socioeconomic predictors for the use of these therapies, in order to identify and understand potential barriers to access in the United States. Methods: We used the NCDB for all patients aged 18-years and older who were diagnosed with metastatic melanoma of cutaneous origin from 2004-2014. Patients were included if they had distant metastases or American Joint Committee on Cancer (AJCC) Stage IV. Sociodemographic data, including race, age, insurance status, facility providing care, Charlson/Deyo comorbidity score11, and education by patient’s zip code, were collected. Results: In patients under age 65 with a Charlson-Deyo score of zero, immunotherapy utilization ranged between 8.5–13.4% during 2004 to 2010. In 2011, the usage increased to 16.5% and rose every subsequent year to 29.6% in 2014. Patients were less likely to receive immunotherapy if they had no insurance, were of older age, or received care at a community practice rather than an academic center. Those who received immunotherapy had greater overall survival compared with those who did not. Conclusions: Immunotherapy and targeted agents have become standard of care in those with metastatic melanoma. Adoption of immunotherapy use for metastatic melanoma has been relatively slow despite evidence showing an overall survival benefit; our analysis suggests this is explained in part by socioeconomic barriers.