Background Acute myeloid leukemia (AML) in elderly patients is a poor prognosis disease due to many factors that include disease biology, high risk of treatment-related mortality, co-morbid illnesses, geriatric syndromes, and psychosocial factors such as cognitive decline and social isolation. Such factors make it difficult to administer intensive chemotherapy regimens needed to achieve a durable response in older patients with AML. CPX-351, Vyxeos®, is a fixed combination of the antineoplastic drugs cytarabine and daunorubicin, encased together inside the liposome in a 5:1 molar ratio. CPX-351 preferentially targets leukemic cells to a greater degree than non-leukemic cells in the bone marrow, leading to decreased cytotoxicity against normal hematopoietic cells. Methods Thirty newly-diagnosed AML patients aged ≥65yrs, without upper age limit restriction, were treated with CPX-351 as a first intensive therapy (Table 1). The primary efficacy endpoint was overall survival (OS) and the primary safety endpoint was 30-day mortality. Secondary efficacy endpoints included response rate and duration of response and assessment of the relationship between cognitive function, quality of life, and treatment outcome. Cognitive function was measured using the Montreal Cognitive Assessment (MOCA) and the Blessed Orientation-Memory-Concentration (BOMC) tests. Quality of life was assessed using the Functional Assessment of Cancer Treatment- Leukemia (FACT-Leu) questionnaire. Results Eleven patients (36.6%) achieved complete remission (CR) and 5 patients (16.6%) achieved complete remission with incomplete platelet recovery (CRi). Of these patients, 8 (26.6%) received stem cell transplants. 2 patients (6.6%) died within 30-days. Of the patients who achieved CR/CRi, 5 (16.6%) relapsed after a median remission duration of 120 days. OS at Day-30 was 93.3% and at Day-60 was 86.6%. Median OS for all patients was 14.5 months (Figure 1). Median event-free survival for all patients (defined as the time from Day 1 of treatment to persistent disease (PD) or death) has not been met at 20 months. Patients who had received prior low intensity therapy (n=16) versus those who were treatment naïve (n=14) had a significantly decreased OS (p= 0.027) (Figure 2). Median OS for previously treated patients was 5.6 months, in contrast to treatment naïve patients, who have not met median OS at 20 months. Patients who had received prior low intensity therapy also had a lower CR+CRi rate of 31.5%, in comparison to treatment naïve patients who had a CR+CRi rate of 78.5%. The most common adverse events attributable to CPX-351 were Grade 1-2 rash (20 patients, 66.7%) and Grade 2-3 decrease in left ventricular ejection fraction (LVEF) (6 patients, 20%) (Table 2). Of patients who experienced a decrease in LVEF, 5 recovered to baseline after a median of 59 days. There was a significant increase in BOMC score from baseline (BL) to the end of the first induction (EOI) (p=0.029) (Figure 3) for 29 patients. There was also a non-significant increase in the total MOCA score from BL to EOI (p=0.056) (Figure 3) for 29 patients. In addition, there was an expected overall upward trend in total FACT-Leu score from BL to EOI (n=19). There was also an upward trend in total FACT-Leu score from BL to EOI in patients who achieved CR/CRi (n=12). In contrast, there was a downward trend in total FACT-Leu score from BL to EOI in patients with PD (n=7) (Figure 4). Conclusion: Elderly AML patients can be treated safely with CPX-351 with a low 30-day mortality, a CR+CRi rate of 53.3%, and a prolonged duration of treatment response with median EFS not met at 20m. Although sample sizes for questionnaire data were small, the observed trends toward improved BOMC, MOCA, and FACT-Leu scores suggest that there may be functional cognitive improvement and improved quality of life for elderly patients treated with CPX-351. Disclosures Ritchie: Genentech: Other: Advisory board; Tolero: Other: Advisory board; Pfizer: Other: Advisory board, travel support; agios: Other: Advisory board; Celgene: Other: Advisory board; Jazz Pharmaceuticals: Research Funding; Celgene, Novartis: Other: travel support; AStella, Bristol-Myers Squibb, Novartis, NS Pharma, Pfizer: Research Funding; Ariad, Celgene, Incyte, Novartis: Speakers Bureau; Celgene, Incyte, Novartis, Pfizer: Consultancy. Lee:Helsinn: Consultancy; Jazz Pharmaceuticals, Inc: Consultancy; Roche Molecular Systems: Consultancy; AstraZeneca Pharmaceuticals: Consultancy; Karyopharm Therapeutics: Consultancy; Ai Therapeutics: Research Funding. Desai:Cellerant: Consultancy; Astex: Research Funding; Astellas: Honoraria; Sanofi: Consultancy; Celgene: Consultancy. Roboz:Sandoz: 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; Trovagene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche/Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Orsenix: Consultancy, Membership on an entity's Board of Directors or advisory committees; Otsuka: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; MEI Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Eisai: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amphivena: Consultancy, Membership on an entity's Board of Directors or advisory committees; Argenx: Consultancy, Membership on an entity's Board of Directors or advisory committees; Actinium: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astex: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Background Research is scarce on the prospective predictors of first onset suicidal thoughts and behaviors (STB) and the accuracy of these predictors in university students, particularly in low‐and‐middle income countries. Therefore, we assessed the 1‐year incidence of STB among first‐year students, a broad range of prospective predictors of STB incidence, and evaluated the prediction accuracy of a baseline multivariate risk prediction model to identify students at highest risk for STB onset over the subsequent 12 months. Methods Students (n = 3238) from 13 universities in Mexico completed an online survey developed for the World Mental Health International College Student Surveys in their first year and again 12 months after. We ran generalized linear models and receiver operator curves. Results The 1‐year incidence of suicidal ideation, plan and attempt was 8.53%, 3.75%, and 1.16%, respectively. Predictors in final models were female sex (ideation only), minority sexual orientation (ideation only), depression, eating disorders, ADHD (ideation and plan), ongoing arguments or breakup with a romantic partner (ideation only), emotional abuse (ideation only), parental death (ideation, plan), not Catholic/Christian (ideation, plan), not having someone to rely on, psychotic experiences (plan only), and insufficient sleep (attempt only). Prediction accuracy for ideation, plan and attempt was area under the curve = 0.76, 0.81 and 0.78, respectively. Targeting the top 10% of students at highest risk could reduce STB in the subsequent year up to 36%. Conclusions By assessing these risk/protective factors in incoming students we identified students at greatest risk for developing STB to whom suicide prevention strategies could be targeted.

Background: Gastrointestinal dysbiosis has been associated with unfavorable clinical outcomes after allogeneic stem cell transplantation, but its clinical significance in patients receiving induction chemotherapy for AML has not been well defined. We therefore explored changes in microbial diversity and their potential impact on clinical outcomes in patients with newly-diagnosed AML undergoing standard intensive induction chemotherapy. Methods: Stool samples were obtained from 64 newly-diagnosed AML patients receiving induction chemotherapy at Weill Cornell Medicine/The New York Presbyterian Hospital from November 2015 to May 2019. A total of 140 serial samples were analyzed and categorized into three treatment time-points (±7 days): Baseline (n=64), Day 14 after chemotherapy initiation (n=51), and Day 30 after chemotherapy initiation (n=25). Clinical characteristics and treatment outcomes were collected. DNA was extracted from stool samples and sequencing of the V4 region of the bacterial 16S rRNA genes was performed using an Illumina MiSeq platform. Alpha microbial diversity was measured by the Shannon Index, Simpson Index, and the observed number of Operational Taxonomic Units (OTUs). The Friedman test was used to assess for changes in alpha diversity from baseline to Day 14 to Day 30 samples. Wilcoxon rank-sum tests were used to compare alpha diversities between groups of dichotomized clinical variables, including gender, age, early antibacterial use, diarrhea, bloodstream infections, and achieving a complete response (CR). The Kruskal Wallis one-way test of variance was used to compare differences in microbial diversity between ELN risk categories. A multivariate logistic regression model was applied to assess associations between the degree of change in diversity from baseline to day 14 and clinical outcomes. Results: Clinical characteristics are summarized in Table 1. Intensive chemotherapy consisted of 7+3 (cytarabine/anthracycline), CPX-351, or 7+3 combined with other therapies. 49 (77%) patients achieved CR or CRi (CR with incomplete count recovery) and 24 (38%) had bloodstream infections during their hospital course. Shannon and Simpson diversity indices and OTUs are shown in Figure 1. There was a significant decline in median microbiome alpha diversities measured by all indices among baseline, day 14, and day 30 samples (Shannon: p = 0.0003; Simpson: p = 0.0003; OTU: p<0.0001). The median change in diversity from baseline to day 14 samples were: Shannon (median: -0.932, range: -3.714 to +1.96), Simpson (median: -0.210, range: -0.947 to +0.689), and OTU (median -62, range: -270 to 93). 24 patients (38%) received antibacterial treatment prior to day 14. However, antibacterial therapy during this time was not associated with change in diversity using any of the indices. Decrease in alpha diversity from baseline to day 14 samples by Shannon index was associated with the achievement of CR/CRi (p = 0.023) (Figure 2). Subsequent multivariate regression analysis showed significant correlations between amount of Shannon diversity decrease from baseline to day 14 and CR/CRi, independent of age, ELN risk, and baseline diversity (Odds ratio: 0.053, (95% CI: 0.001 to 0.467, p = 0.049). Achievement of CR/CRi was significantly correlated with a decrease of microbiome diversity from baseline to day 14 (Median = -1.111), whereas failure to achieve CR/CRi was correlated with an increase in microbiome diversity from baseline to day 14 (Median = +0.199). There were no significant correlations between levels of baseline, day 14, or day 30 microbiome diversity and age (>60 vs. ≤60), ELN risk categories, diarrhea, bloodstream infections, or CR/CRi using any of the indices. There were no significant correlations between decrease in diversity from baseline to Day 14 samples and diarrhea or bloodstream infections. (Figure 2) Conclusion: Gut microbial diversity declines in patients receiving intensive induction chemotherapy for AML throughout their hospitalization, even in the absence of antibacterial therapy. Overall decrease in diversity at day 14 is associated with achievement of remission, independent of age, ELN risk, and baseline diversity. In this cohort, neither decreased microbial diversity nor a decline in microbial diversity was associated with adverse clinical outcomes. Additional study of the impact of the gut microbiome on outcomes in patients with AML is warranted. Disclosures Lee: Roche Molecular Systems: Consultancy; Jazz Pharmaceuticals, Inc: Consultancy; Helsinn: Consultancy; Karyopharm Therapeutics: Consultancy; Ai Therapeutics: Research Funding; AstraZeneca Pharmaceuticals: Consultancy. Ritchie:Genentech: Other: Advisory board; Celgene: Other: Advisory board; AStella, Bristol-Myers Squibb, Novartis, NS Pharma, Pfizer: Research Funding; Celgene, Novartis: Other: travel support; Jazz Pharmaceuticals: Research Funding; Pfizer: Other: Advisory board, travel support; agios: Other: Advisory board; Tolero: Other: Advisory board; Celgene, Incyte, Novartis, Pfizer: Consultancy; Ariad, Celgene, Incyte, Novartis: Speakers Bureau. Desai:Sanofi: Consultancy; Celgene: Consultancy; Cellerant: Consultancy; Astex: Research Funding; Astellas: Honoraria. Roboz:AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Actinium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amphivena: Consultancy, Membership on an entity's Board of Directors or advisory committees; Argenx: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astex: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees; Eisai: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; MEI Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Orsenix: Consultancy, Membership on an entity's Board of Directors or advisory committees; Otsuka: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche/Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sandoz: 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; Trovagene: Consultancy, Membership on an entity's Board of Directors or advisory committees.

7044 Background: This study enrolled older patients without age limitation to intensive chemotherapy with CPX 351 allowing for prior treatment with low intensity regimens for MDS or AML. Methods: 30 patients aged ≥65yrs with diagnosed AML received up to two induction cycles and consolidation cycles of CPX-351 as a first intensive therapy. The primary efficacy endpoint was overall survival and the primary safety endpoint was 30-day mortality. Secondary efficacy endpoints included response rate and duration, and assessment of the relationship between cognitive function and treatment outcome. Although the primary efficacy endpoint data is pending, these interim results describe promising primary safety and efficacy endpoint results. Of the 30 patients enrolled, 10 patients (33.3%) were ≥75yrs old, 13 patients (43.3%) had had previous hematologic malignancies, 17 patients (56.6%) had adverse ELN risk stratification, and 16 patients (53.3%) had failed to respond to previous non-intensive treatments. In addition, all patients had an average of 2.1 co-morbid medical conditions. Results: 14 patients (47%) achieved best response criteria, with 12 patients (40.0%) achieving complete remission (CR) and 2 patients (6.6%) achieving complete remission with incomplete platelet or neutrophil recovery (CRi). 6 patients (20%) had a morphologic leukemia free state with pancytopenia and 10 patients had persistent disease. 8 patients (26.6%) went to stem cell transplant. 2 patients (6.6%) died within 30-days. Although final analysis on adverse events data is pending, 6 patients (20%) experienced a Grade 2 decrease in left ventricular ejection fraction (LVEF) at the end of first induction. Conclusions: These results suggest that in elderly AML patients regardless of age and prior treatment with non-intensive chemotherapy can be treated safely with CPX 351 with low 30 day mortality. CR in these patients is 40% with 26% going forward to stem cell transplant. Complete data will be assessed for OS and rate of MRD positivity. The relationship of cognitive and social factors to outcome will also be addressed.