Citations

Background: We aimed to test the hypothesis that peripheral endothelial dysfunction induced by mental stress may predict cardiovascular events after acute coronary syndrome beyond traditional cardiovascular disease risk factors. Methods: This was a prospective study in which 417 patients who had acute coronary syndrome were enrolled in two sites at the US and Qatar. Cardiovascular disease risk factors such as past medical history, blood pressure, heart rate, peripheral endothelial dysfunction, and response to three different mental stress examinations (Stroop Color Word, Arithmetic, and Spiral Omnibus) as assessed by ratio of reactive hyperemia tonometry (EndoPAT) with stress over EndoPAT at rest were obtained at baseline. Major adverse cardiac events were then recorded at 1 year after the index event. Results: There were no differences in baseline peripheral endothelial dysfunction or vascular response to mental stress between the US vs. Qatar patients. Women were more likely to experience major adverse cardiac events in the year following acute coronary syndrome (relative risk 2.42, 95% confidence interval 1.53–3.84, P = 0.044), and had a significantly lower mental stress ratio compared to women who did not (1.0 ± 0.17 vs. 1.20 ± 0.17, P = 0.04). In multivariate analyses stratified by sex, baseline peripheral endothelial dysfunction (EndoPAT < 1.7) (χ2 = 8.0, P = 0.005) and mental stress ratio (χ2 = 7.7, P = 0.006), were independently predictive of major adverse cardiac events in women, but not men. Conclusion: The current study demonstrates that in women both baseline endothelial function and vascular function in response to mental stress ratio are predictive of worse cardiovascular disease outcomes 1 year after acute coronary syndrome. The study may suggest an important mechanism for adverse clinical outcomes in women following acute coronary syndrome.

ObjectiveThe objective of this study is to compare biologic drug discontinuation rates for older‐ versus younger‐onset rheumatoid arthritis (YORA) because this is a key outcome measure that could impact prescribing practices.MethodsWe performed a retrospective medical record review of all patients who fulfilled the 1987 American College of Rheumatology (ACR) criteria for adult‐onset rheumatoid arthritis (RA) in 1999‐2013 among residents of a geographically defined area, with follow‐up until death, migration, or July 1, 2017. Discontinuation rates were estimated using cumulative incidence adjusted for the competing risk of death.ResultsA total of 240 cases of elderly‐onset rheumatoid arthritis (EORA) and 366 cases of YORA were identified (65% and 73% female, respectively; P = 0.025). Cumulative incidence of biologic initiation was lower among the EORA cohort compared with the YORA cohort (18% vs 33%, respectively, at 10 years after RA incidence; P < 0.001). Among those treated with a biologic, years from RA diagnosis to first biologic treatment was not significantly different between the two groups (P = 0.62). Drug survival of first biologic was 64% at 1 year (95% confidence interval [CI]: 45%‐77%) and 53% at 2 years (95% CI: 33%‐66%) for EORA, compared with 61% at 1 year (95% CI: 50%‐69%) and 45% at 2 years (95% CI: 34%‐53%) for YORA (P = 0.75). Concurrent glucocorticoid use at initiation of first biologic was statistically and significantly associated with a lower risk of discontinuation in EORA (hazard ratio 0.21; 95% CI: 0.08‐0.53) but not in YORA (interaction P = 0.04).ConclusionDrug survival rates of biologic medications did not differ significantly between patients with EORA and YORA.

Abstract Background The etiological basis of glioma is poorly understood. We have used genetic markers in a Mendelian Randomisation (MR) framework to examine if lifestyle, cardiometabolic and inflammatory factors influence the risk of glioma. This methodology reduces bias from confounding and is not affected by reverse causation. Methods We identified genetic instruments for 37 potentially modifiable risk factors and evaluated their association with glioma risk using data from a genome-wide association study of 12,488 glioma patients and 18,169 controls. We used the estimated odds ratio of glioma associated with each of the genetically defined traits to infer evidence for a causal relationship with the following exposures: lifestyle and dietary factors (height, plasma IGF-1, blood carnitine, blood methionine, blood selenium, blood zinc, circulating adiponectin, circulating carotenoids, iron status, serum calcium, vitamin [A1, B12, B6, E and 25-hydroxyvitamin D], fatty acids levels [mono-unsaturated, omega-3 and omega-6] and circulating fetuin-A); cardiometabolic factors (birth weight, HDL cholesterol, LDL cholesterol, total cholesterol, total triglycerides, basal metabolic rate, body fat percentage, body mass index, fasting glucose, fasting proinsulin, HbA1C levels, diastolic and systolic blood pressure, waist circumference, waist-to-hip ratio) were included; inflammatory factors (C-reactive protein (CRP), plasma IL-6 sRa and serum IgE). Results After correction for the testing of multiple potential risk factors and excluding associations driven by one single nucleotide polymorphism (SNP) no significant association with glioma risk was observed (i.e. PCorrected > 0.05). Conclusions This study did not provide evidence supporting any of the 37 factors examined as having a significant influence on glioma risk.

AbstractCurrent published guidelines for perioperative pharmacy services have limited information on the development and implementation of a robust clinical pharmacy program across the surgical continuum of care. This publication defines the responsibilities and scope of practice of the Perioperative Clinical Pharmacist (PCPh), supporting the PCPh as a critical member of the interprofessional surgical patient care team. Opportunities for pharmacist role integration into perioperative medication management processes are described along with published examples of successful PCPh practice models, including those with interventions targeted toward Enhanced Recovery Pathways (ERP). Recommended training and competencies for future and practicing perioperative pharmacists, in addition to considerations for precepting and scholarly activities, are also outlined. Finally, future developments in perioperative pharmacy practice are discussed, including technological advancements, improved predictive models, and expansion of collaborative practice agreements.

Abstract Background Patients with type 2 diabetes are at an increased risk of cardiovascular events compared to individuals without diabetes. The role glycemic control plays in reducing cardiovascular risk remains uncertain. Coronary microvascular dysfunction (CMD) is more frequent in women compared to men, is prevalent in patients with type 2 diabetes and is linked to adverse cardiovascular events. We compared the association between CMD and glycemic control across sexes in patients with chest pain and non-obstructive coronary artery disease (CAD). Methods Patients with chest pain who were found to have non-obstructive CAD (stenosis <40%) at angiography underwent an invasive assessment of endothelial-independent and endothelial–dependent coronary microvascular function. Using a Doppler guidewire, endothelial-independent microvascular function was assessed by measuring the coronary flow velocity in response to intracoronary adenosine and comparing this to baseline to calculate the coronary flow reserve ratio (CFRAdn). A CFRAdn ≤2.5 was considered abnormal. Endothelial-dependent microvascular function was assessed by measuring the percent change in coronary blood flow in response to intracoronary infusions of acetylcholine (%ΔCBFAch), with a %ΔCBFAch ≤50% considered abnormal. Patients were classified as having normal versus abnormal CFRAdn and %ΔCBFAch. Measurements of HbA1c and fasting serum glucose were obtained at the time of catheterization and compared between groups after stratification by sex. Results Between 1993 and 2012, 1,469 patients (mean age 50.4 years, 35% male) underwent coronary angiography and invasive testing for CMD, of which 129 (8.8%) had type 2 diabetes. Fifty one (39.5%) had an abnormal %ΔCBFAch and 49 (38.0%) had an abnormal CFRAdn. Conventional cardiovascular risk factors did not vary significantly between groups. Females with an abnormal CFRAdn or abnormal %ΔCBFAch had a significantly higher HbA1c compared to those with a normal CFRAdn or %ΔCBFAch respectively: HbA1c % (standard deviation) 7.4 (2.1) vs. 6.5 (1.1), p=0.035 and 7.3 (1.9) vs. 6.4 (1.2), p=0.022, respectively. Females with an abnormal CFRAdn had significantly higher fasting serum glucose concentrations compared to those with a normal CFRAdn: fasting serum glucose mg/dL (standard deviation) 144.4 (55.6) vs. 121.9 (28.1), p=0.035. These effects were not observed in men. Amongst female diabetics, a higher HbA1c was significantly associated with any CMD after adjusting for covariates: odds ratio (95% confidence interval) 1.69 (1.01 – 2.86) p=0.049; and a fasting serum glucose >140 mg/dL was significantly associated with an abnormal CFRAdn, 4.28 (1.43–12.81). Conclusion Poor glycemic control is associated with CMD in females with diabete who present with chest pain and non-obstructive CAD. These findings highlight the importance of sex-specific risk stratification models and treatment strategies when managing cardiovascular risk in diabetics. Acknowledgement/Funding Mayo Foundation

Abstract Background: Modern clinical practice places time restrictions on the amount of information and processing that can be done in a typical office visit. Meeting patient needs within the healthcare system is challenging, contributing to patient (pt) and clinician dissatisfaction and potential suboptimal outcomes. We developed an electronic point-of-care case management system for cancer patients. The system's goal is to obtain patient-reported quality of life (PROQOL) outcomes and provide clinicians with information regarding QOL issues to address. We tested this system in a prospective randomized study against usual care (UC). The primary objective was to determine if PROQOL system would improve mean QOL over time. Methods: Eligible pts were adults with multiple myeloma (MM) or light amyloidosis (AL), seen at Mayo Clinic. Pts were randomized 2:1 to PROQOL system or usual care. PROQOL system was offered prior to every visit. Pts select from various categories about their single biggest concern, and receive a printed list of actionable resources based on selected concern. Clinicians also receive the PROQOL results to review with pts. Providers and pts randomized to PROQOL completed a "was it worth it survey" (WIWI). An 8 item Linear Analogue Self-Assessment was used to assess QOL, the primary endpoint. Secondary endpoints included distribution of choices of most important concern and their relationship to demographic and clinical variables. The study was powered to detect a 0.5 standard deviation difference in QOL between groups. Results: There were 233 patients enrolled (171 MM, 62 AL) in this study between July 1, 2016 and April 17, 2018. Median age was 65 years (range 31-87), and 59% were male. Median time from diagnosis to study consent was 37 months (PROQOL 36.3 versus UC 39.6). Median follow up for all patients was 15 months (range: 0.7-22 months), and median follow up for PROQOL pts was 16 months and 14 months for UC pts (p=0.027). There were 25 pts that have died since enrollment and 208 alive. No statistical significant difference in QOL between PROQOL and UC (median QOL 7 vs 7, p=0.75). The most prevalent main concerns selected were Physical Health (37%) and Cancer and Diagnosis (27%), the pattern remained even when pts were given the option to pick a second major concern 26% and 20% respectively. No other concern was listed more than 8% at baseline. All category selections and percentages are shown in the Figure. The average time to complete the instrument was 6 minutes. Pts found the PROQOL system was worth their time (75%), they would choose it again (87%) and recommend it to others (82%). Eighty-two percent of clinicians did not think the PROQOL tool negatively impacted their practice and 75% believed they may see improvement in pt wellbeing. Discussion: The PROQOL system was well received by pts and clinicians but did not improve QOL relative to UC in this study. The PROQOL demonstrates that majority of patients strongly desire more information regarding ongoing therapy, clinical trials, prognosis and toxicity. Further investigation is needed to understand whether communication is limited by time or mechanism of information delivery, such as verbal or written, or whether it should be undertaken in a separate allied health care visit. Figure. Figure. Disclosures Gertz: spectrum: Consultancy, Honoraria; Abbvie: Consultancy; Research to Practice: Consultancy; annexon: Consultancy; Medscape: Consultancy; Physicians Education Resource: Consultancy; Amgen: Consultancy; janssen: Consultancy; Alnylam: Honoraria; Teva: Consultancy; Apellis: Consultancy; Ionis: Honoraria; celgene: Consultancy; Prothena: Honoraria. Kumar:Novartis: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding. Dingli:Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Millennium Takeda: Research Funding; Millennium Takeda: Research Funding; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.. Lacy:Celgene: Research Funding. Dispenzieri:Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK: Research Funding.

Abstract Introduction REGN1979 is an anti-CD20 x anti-CD3 bispecific IgG4 antibody (Ab) modified to reduce Fc binding. Engaging both targets results in CD20-specific, local T-cell activation and cytotoxicity, a mechanism of action distinct from standard anti-CD20 Abs. We report updated promising efficacy results of a Phase 1 trial of REGN1979 in patients (pts) with relapsed/refactory (R/R) B-NHL previously treated with anti-CD20 Abs. Methods The primary objectives of the study are to determine safety, tolerability, and occurrence of dose limiting toxicities (DLTs). Other objectives include assessment of preliminary antitumor activity, pharmacokinetics (PK), and pharmacodynamics. Eligible pts with R/R NHL must have received at least 1 prior CD20-directed therapy. Treatment consists of 12 weekly doses of REGN1979 followed by every 2 week dosing for 12 doses for a total of 36 weeks. Guidelines are provided for management of cytokine release syndrome (CRS) and include steroids and/or tocilizumab at investigator discretion. Results As of June 1, 2018, 54 pts with B-NHL were treated with REGN1979 monotherapy: DLBCL (pt number [n]=30), FL (n=16), MCL (n=5), MZL (n=2), and WM (n=1). The median number of prior regimens was 3 (range, 1-11); 41 pts were refractory to their last prior systemic therapy, 18 had bulky disease, and 6 had prior HSCT. Pts were treated with REGN1979 0.03-27 mg and received a median of 7 (range, 1-24) doses. Eight pts remain on treatment, 13 completed treatment, and 33 discontinued therapy prior to the planned 36 wks (majority [n=22] due to progressive disease [PD]). There have been no DLTs to date. The most common treatment-related treatment-emergent adverse events (TR-TEAEs) included infusion-related reactions (IRR) or CRS; 26 pts experienced CRS (Grade 1-2, n=23; Grade 3, n=3) with a median duration of CRS of 2 (range 1-15) days. Six pts received tocilizumab. The severity of CRS symptoms declined through optimized pre-medication even with REGN1979 dose escalation. Other common Grade ≥3 TR-TEAEs were lymphocytopenia/ decreased lymphocyte count (n=8); neutropenia/ decreased neutrophil count (n=7); and thrombocytopenia/ decreased platelet count, hypotension, hypophosphatemia, and anemia (each n=3). Seventeen pts experienced a nervous system event including headache, dizziness, paraesthesia, dysgeusia, and peripheral neuropathy with no Grade ≥3 events; no neurologic event required termination of study drug. Seven pts died on study: PD (n=5), gastric perforation (n=1), and cardiac arrest (n=1). TEAEs leading to premature discontinuation of REGN1979 were Grade 3 fatigue (n=1), Grade 3 hemolysis (n=1), and Grade 2 pyrexia/Grade 2 tachycardia (n=1). Among 27 pts treated with REGN1979 ≥5 mg (dose associated with tumor killing in pre-clinical data), the overall response rate (ORR) was 55.6% (5 complete response [CR] and 10 partial response [PR]; Table/Figure). Responses were seen in 7/7 FL Grade 1-3a pts (5 CR, 2 PR), 6/15 DLBCL pts (all PR), 2/2 MCL pts (all PR). At 18 mg and 27 mg of REGN1979, 4 of 4 pts with DLBCL had best response of PR. Post data cut-off, 1 pt with a DLBCL best response of PR converted to CR. PK and pharmacodynamic assessments suggest that for pts treated with REGN1979 5-18 mg, best exposures in the first 3 weeks appear to linearly increase with dose. In pts treated with up to REGN1979 18 mg, a maximum mean Ctrough of 1.6 mcg/mL was observed in the first 3 weeks of weekly dosing. Studies of peripheral blood biomarkers demonstrated depletion of peripheral B lymphocytes, transient margination of circulating T-cells, and elevated circulating cytokines following REGN1979 dosing. Increased peak cytokine levels (IL-6, IL-10, and TNF-alpha) were observed in pts with CRS. Immunohistological analysis of malignant lymph node tissue demonstrated a decrease of CD20 expression in responding pts; among the responders, subsequent relapse was associated with either maintenance of CD20 expression or further CD20 loss, suggesting antigen-dependent and independent disease escape mechanisms. Conclusions REGN1979 displays efficacy and an acceptable safety profile in pts with R/R B-NHL. Most TR-TEAEs were IRR/CRS and have been well managed with supportive care. No significant neurological toxicity has been observed. At doses of 5-27 mg of REGN1979, the preliminary ORR was 100% in pts with FL Grade 1-3a and 40.0% in pts with DLBCL. This promising efficacy warrants further clinical investigation. Disclosures Bannerji: Regeneron Pharmaceuticals, Inc.: Consultancy; AbbVie, Inc.: Consultancy. Arnason:Regeneron Pharmaceuticals, Inc.: Consultancy. Advani:Bayer Healthcare Pharmaceuticals: Other: Consultancy/Advisory Role; Janssen Pharmaceutical: Other: Institutional Research Support; Bristol Myers Squibb: Other: Consultancy/Advisory role and Institutional Research Support; Pharmacyclics: Other: Institutional Research Support; Takeda: Other: Consultancy/Advisory Role; Millenium: Other: Institutional Research Support; Gilead/Kite: Other: Consultancy/Advisory Role; Infinity: Other: Institutional Research Support; Merck: Other: Institutional Research Support; Forty Seven, Inc: Other: Institutional Research Support; Cell Medica: Other: Consultancy/Advisory Role; Agensys: Other: Institutional Research Support; Celgene: Other: Institutional Research Support; Seattle Genetics: Other: Consultancy/Advisory role, Institutional Research Support; Kura: Other: Institutional Research Support; Roche/Genentech: Other: Consultancy/Advisory Role, Institutional Research Support; Kyowa: Other: Consulting/Advisory Role; Regeneron Pharmaceuticals, Inc.: Other: Institutional Research Support; Autolus: Other: Consultancy/Advisory Role; AstraZeneca: Other: Consultancy/Advisory Role. Brown:Acerta / Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Research Funding; Pharmacyclics: Consultancy; Celgene: Consultancy; Genentech: Consultancy; TG Therapeutics: Consultancy; Morphosys: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Abbvie: Consultancy; Gilead: Consultancy, Research Funding; Sun Pharmaceutical Industries: Research Funding; Sunesis: Consultancy; Loxo: Consultancy; Beigene: Membership on an entity's Board of Directors or advisory committees; Invectys: Membership on an entity's Board of Directors or advisory committees; Roche/Genentech: Consultancy; Boehringer: Consultancy. Allan:Genentech: Membership on an entity's Board of Directors or advisory committees; Verastem: Membership on an entity's Board of Directors or advisory committees; Sunesis: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy. Ansell:Bristol-Myers Squibb: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Merck & Co: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Celldex: Research Funding; Takeda: Research Funding; Pfizer: Research Funding. O'Brien:Kite Pharma: Research Funding; Aptose Biosciences Inc.: Consultancy; Pharmacyclics: Consultancy, Research Funding; GlaxoSmithKline: Consultancy; Astellas: Consultancy; Sunesis: Consultancy, Research Funding; Alexion: Consultancy; Amgen: Consultancy; TG Therapeutics: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Vaniam Group LLC: Consultancy; Regeneron: Research Funding; Janssen: Consultancy; Celgene: Consultancy; Abbvie: Consultancy; Acerta: Research Funding; Gilead: Consultancy, Research Funding. Chavez:Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Research Funding; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Humanigen: Consultancy. Lowy:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Charnas:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Sternberg:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Ambati:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Adriaens:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Ufkin:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Yan:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Li:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Navarro:Regeneron Pharmaceuticals, Inc.: Employment. Gasparini:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Jankovic:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Fiaschi:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Zhang:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Hamon:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Thurston:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Topp:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees, Research Funding; Boehringer Ingelheim: Research Funding; Regeneron Pharmaceuticals, Inc.: Honoraria, Research Funding.

Abstract Background: Trabectedin is an FDA-approved DNA minor groove binder (MGB) that has activity against translocation-associated sarcomas. Lurbinectedin is a next-generation MGB with pre-clinical activity against myeloid leukemia cells. A dose-finding phase 1 clinical trial was performed in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) with further assessment of safety and tolerability. Methods: Forty-two patients with relapsed/refractory AML/MDS received lurbinectedin administered as a 1-hour intravenous infusion in a 3+3 study design. Two dosing schedules were used: 3.5 mg, 5 mg, 7 mg, or 6 mg on days 1 and 8 or 2 mg, 3 mg, 1 mg, or 1.5 mg for 3 consecutive days on days 1 to 3. Patients 18 years or older with a diagnosis of advanced, relapsed/refractory AML (non-acute promyelocytic leukemia) and MDS were eligible and treated on study. Eligible patients had adequate hepatic, renal, and cardiac function and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Patients with uncontrolled infection, human immunodeficiency virus, cardiac and neurological disorders, or those who were pregnant were ineligible. Clinical trial information: NCT01314599. Results: Three patients experienced dose-limiting toxicities of rhabdomyolysis (grade 4), hyperbilirubinemia (grade 3), and oral herpes (grade 3) with the days 1 and 8 schedule. Otherwise, adverse events mainly consisted of gastrointestinal manifestations (n=11), febrile neutropenia/infections (n=4), pulmonary toxicity (n=2), and renal failure (n=2). The most common laboratory abnormalities observed were an increase in creatinine (93%) and anemia, neutropenia, and thrombocytopenia (100%). Overall, 33 of 42 patients (79%) had reduction in blasts in peripheral blood or bone marrow. One patient achieved a partial response and two patients a morphologic leukemia-free state. Most (n=30, 71%) were discontinued due to progressive disease. Early deaths occurred from disease-related causes that were not attributable to lurbinectedin. Four patients with a chromosome 11q21-23 abnormality had significantly greater bone marrow blast reduction than those without such abnormality, with decrease of 31±14% (n=4) vs. 8±8% (n=16), respectively (P=0.04). Conclusions: Overall, lurbinectedin was safe and tolerated using the schedules and dose levels tested. While no sustained remissions were observed, single-agent lurbinectedin was transiently leukemia suppressive for some patients. Disclosures Rodríguez: PharmaMar: Employment. Ravandi:Bristol-Myers Squibb: Research Funding; Jazz: Honoraria; Abbvie: Research Funding; Seattle Genetics: Research Funding; Abbvie: Research Funding; Amgen: Honoraria, Research Funding, Speakers Bureau; Orsenix: Honoraria; Seattle Genetics: Research Funding; Astellas Pharmaceuticals: Consultancy, Honoraria; Sunesis: Honoraria; Orsenix: Honoraria; Macrogenix: Honoraria, Research Funding; Astellas Pharmaceuticals: Consultancy, Honoraria; Jazz: Honoraria; Xencor: Research Funding; Bristol-Myers Squibb: Research Funding; Amgen: Honoraria, Research Funding, Speakers Bureau; Macrogenix: Honoraria, Research Funding; Xencor: Research Funding; Sunesis: Honoraria. Daver:Sunesis: Consultancy; Alexion: Consultancy; Daiichi-Sankyo: Research Funding; BMS: Research Funding; ImmunoGen: Consultancy; Kiromic: Research Funding; Incyte: Research Funding; Pfizer: Consultancy; Incyte: Consultancy; ARIAD: Research Funding; Karyopharm: Consultancy; Pfizer: Research Funding; Karyopharm: Research Funding; Novartis: Consultancy; Sunesis: Research Funding; Novartis: Research Funding; Otsuka: Consultancy. Jain:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Research Funding; Infinity: Research Funding; Pfizer: Research Funding; Novimmune: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologioes: Research Funding; Pharmacyclics: Research Funding; Incyte: Research Funding; Verastem: Research Funding; Seattle Genetics: Research Funding; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Research Funding; Astra Zeneca: Research Funding; Servier: Research Funding; Celgene: Research Funding; Seattle Genetics: Research Funding; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Infinity: Research Funding; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Cellectis: Research Funding; ADC Therapeutics: Research Funding; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologioes: Research Funding; Pharmacyclics: Research Funding; Cellectis: Research Funding; Verastem: Research Funding; Servier: Research Funding; Abbvie: Research Funding; Incyte: Research Funding; Genentech: Research Funding; Abbvie: Research Funding; BMS: Research Funding; Astra Zeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novimmune: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Maiti:Celgene Corporation: Other: Research funding to the institution. Martinez:PharmaMar: Employment. Siguero:PharmaMar: Employment. Al-Kali:Novartis: Research Funding.

Abstract Background Current literature suggests that the presence and quality of social support may provide meaningful benefits in overall survival of HCT recipients. Further, studies in general oncology and renal transplantation population suggest that married patients have favorable outcomes. Caregivers of HCT recipients are an important source of both instrumental and emotional support, and a reasonable surrogate for presence of social support. Using data from Center for International Blood and Marrow Transplant Research (CIBMTR), we examined the potential influence of marital status (surrogate for caregiver) at the time of HCT on outcomes of HCT. Methods Patients, >40 years of age who underwent either autologous or allogeneic-HCT from 2008 to 2015 were included. Marital status was defined as either 1) Married, 2) Single, never married, 3) Separated/divorced, and 4) Widowed. The probability of OS at 5 years, Grade 2-4 acute GVHD at 100 days and chronic GVHD at 2 years were estimated as appropriate using the Kaplan-Meier method with the log-rank test used for univariate comparisons. Multivariate analysis was performed to determine the association of marital status with these outcomes, while adjusting for clinical and sociodemographic variables. Results We identified 10,226 allogeneic and 5,714 autologous HCT patients; the median follow-up of survivors was 37 months (range 1-102 months) and 40 months (range 1-106 months) respectively. In the allogeneic population, there were n=7,999 married, n=741 single, n=1,175 separated/divorced and n=311 widowed patients. There were n=4,308, n=478, n=695 and n=233 respectively in the autologous population. The baseline characteristics amongst the 4 groups of marital status were comparable. In the allogeneic population, the 5-year probability of OS, 100-day Grade 2-4 acute GVHD, 2-year probability of chronic GVHD were 38% [95%CI (36-39%)], 16% [95%CI (15-17%)]and 46% [95%CI (45-47%)] respectively; while the 5-year probability of OS in the autologous population was 63% [95%CI (61-64%)]. When compared with married patients, single, separated/divorced and widowed patients were not at an increased risk of death [HR 1.09, 95%CI (0.98-1.2); HR 1.01, 95%CI (0.93-1.09); HR 1.09, 95%CI (0.98-1.2)] in the allogeneic setting. Similarly, there was no association of marital status and OS in the autologous setting [HR 1.10, 95%CI (0.92-1.33); HR 1.17, 95%CI (1.01-1.36); HR 1.08, 95%CI (0.86-1.37)] respectively. In contrast, marital status in the allogeneic setting was associated with an increased risk of grade 2-4 acute GVHD in patients who are divorced/separated as compared to married patients [HR 1.13, 95%CI (1.03-1.24)] but not chronic GVHD [HR 0.90, 95%CI (0.80-1.02); HR 0.94, 95%CI (0.86-1.04); HR 0.82, 95%CI (0.68-0.99)] respectively. We did not identify an interaction between marital status and gender. Conclusions Our data suggest the marital status in patients undergoing either autologous or allogeneic HCT is not associated with overall survival or chronic GVHD, while the risk of acute GVHD maybe increased in patients who are divorced/separated. Taken together, the effect of marital status on post-HCT outcomes is negligible when other patient, disease and transplant variables are considered. Alternatively, marital status maybe an imperfect marker for positive social support. Future research should consider measuring social support using validated scales and assess health related quality of life together with health care utilization outcomes to better appreciate the potential impact of social support. Disclosures No relevant conflicts of interest to declare.