Mortality In Pts Research Articles

Mortality trends (1999-2022) in patients with multiple myeloma with pneumonia, influenza, and COVID-19.

7553 Background: Patients (pts) with multiple myeloma (MM) are immunosuppressed either due to the hypogammaglobulinemia and impaired plasma cell function or due to pharmacological management and stem cell transplantations. Consequently, they are at a higher risk of infections. This study aims to evaluate the changes in mortality from COVID-19 (CVD), influenza virus (FLU), and pneumonia (PNA) in MM pts in the era of CVD pandemic. Methods: Using the Wide-ranging Online Data for Epidemiologic Research (WONDER) database from the CDC, we collected mortality data for pts with CVD (U07.1 code), FLU and PNA (J09-J18 codes), and MM (C90.0 code). Using sex and ethnicity-specific stratification, the gathered data made it easier to calculate age-adjusted mortality rates (AAMRs) per 100,000 people. Using the collected data we were able to analyze mortality patterns over the years 1999-2022. Results: Overall, 25,271 MM pts died from CVD, FLU and PNA between 1999 to 2022. The mortality rate remained stable from 1999 to 2019 ranging between 0.4 AAMR per 100,000 to 0.3 AAMR, representing an annual percentage change (APC) of -0.5%. However, the mortality rate increased in 2019, rising from 0.3 AAMR per 100,000 to 0.5 in 2022, with APC of 7%. When evaluating the trends by gender, there was an increase in mortality among male pts, rising from 0.4 AAMR per 100,000 to 0.7 between 2019 and 2020, while the increase among females was minimal, from 0.3 AAMR per 100,000 to 0.4. While Hispanic, White, and African American ethnicities mortality increased in 2020-2022, Asian pts maintained a rate of 0.2 AAMR in 2019, 2020, and 2022 (Table). Conclusions: We showed an increase in mortality among pts with MM combined with CVD, FLU, or PNA between 2020 and 2021. It might be attributable to the CVD pandemic, announced by WHO in March 2020. Despite the FDA's approval of the first CVD vaccine in December 2020, the emergence of new CVD variants and limited vaccine availability could have contributed to a continued increase in mortality in 2021.In 2022, we noticed a drop in mortality. It might be explained by the wider accessibility to CVD vaccination or to diminished virulence. Additionally, increased awareness of the importance of CVD vaccinations in immunocompromised pts could also lead to increased FLU vaccination rates. It might explain the downtrending mortality of pts with MM, FLU and PNA only in 2021. This is the first study presenting the mortality trend of MM pts with FLU, PNA and CVD, and comes to highlight the importance of vaccination in immunocompromised MM pts. [Table: see text]

Factors of unfavorable prognosis in patients with non-high risk pulmonary embolism

Abstract Introduction Pulmonary embolism (PE) nowadays is the third leading cause of death in the structure of cardiovascular mortality after myocardial infarction and stroke. Most of patients (pts) with PE are with non-high risk. According to the latest guidelines PESI and sPESI scores are used to predict 30-day outcome of non-high-risk pts. Nevertheless, the question of additional factors which are not included in PESI and sPESI scores and which may be associated with prognosis in such pts remains poorly understood. Purpose To identify factors associated with in-hospital mortality in non-high-risk PE pts. Methods A retrospective analysis of 635 medical cards of pts with diagnosis "PE" hospitalized in our clinical hospital during 2017 – 2023 period. The diagnosis was verified by multispiral computed tomography angiography (CTPA) of pulmonary arteries and/or by autopsy. There were 530 non-high-risk pts (83,4%). Pts were divided into groups: І group - pts who were discharged from hospital with improved status (479 – 90,4%), II group - pts who died in hospital (51 – 9,6%). Clinical, anamnestic, laboratory and instrumental parameters were measured. Statistical analysis was performed. Results According to multivariate analysis of variance, independent factors, which were associated with in-hospital mortality in pts with non-high-risk PE, were: the presence of atrial fibrillation, obesity, age, history of venous thromboembolism, lower levels of O2 saturation, systolic blood pressure (SBP) and higher pulmonary artery pressure (PAP). ROC analysis was performed to determine the thresholds of factors that were associated with in-hospital mortality: SBP ≤124 mmHg, HR≥110 bpm, PAP ≥54 mmHg, age>54 yo. Conclusions The factors which were associated with in-hospital mortality in pts with non-high-risk PE were: age, SBP, history of VTE, obesity, AF; blood saturation level, pulmonary artery pressure level.

Risk factors for adverse outcome among patients with non-high risk pulmonary embolism

The aim – to determine the factors which have influence on hospital mortality in patients with non-high risk pulmonary embolism (PE).Materials and methods. We analysed 635 medical cards of patients (pts) with diagnosis «Pulmonary Embolism (PE)» who were hospitalised to Kharkiv City Clinical Hospital No.8. during 01.01.2017 – 01.01.2023. The inclusion criteria was diagnosis «PE» verified by multispiral computed tomography angiography (CTPA) of pulmonary arteries and/or by autopsy. Among the 635 pts, 530 were non-high risk. The non-high risk pts were divided into 2 groups: Group I – pts who were discharged with improved status (479 – 90.4 %), Group II – pts who died during hospitalisation (51 – 9.6 %). Clinical, anamnestic, biochemical, instrumental parameters, mortality rates were measured; statistical analysis was done.Results and discussion. The independent factors identified by multivariate vector analysis were associated with in-hospital mortality in pts with non-high risk PE: atrial fibrillation (AF), obesity, history of venous thromboembolism (VTE); lower levels of blood oxygen saturation (SpO2), systolic blood pressure (SBP); higher mean pulmonary arterial pressure (PAP); heart rate (HR) ≥ 110 beats/min. An ROC analysis was also performed to determine the thresholds of factors associated with in-hospital mortality in patients with non-high risk PE: SBP ≤ 124 mm Hg, HR ≥ 110 bts/min, mean PAP ≥ 54 mm Hg. Impact of AF on in-hospital mortality was depicted by Kaplan – Meier.Conclusions. Several factors were associated with increased in-hospital mortality in patients with non-high risk PE: age ˃ 54 years, SBP ≤ 124 mm Hg, history of VTE, obesity, AF; SpO2 ≤ 87 %, mean PAP ≥ 54 mm Hg, HR ≥ 110 bpm.

Specific therapies of pulmonary hypertension and prognosis in COVID-19: 18-months analysis of BNP-PL national database

Abstract Introduction The SARS-CoV-2 pandemic had a significant impact on mortality in the group of patients (pts) with pulmonary hypertension (PH). Specific therapies offer the potential to improve COVID-19 survival in this vulnerable population, but data on COVID-19 mortality according to specific PH therapies are scarce. Aim To assess mortality in the course of COVID-19 among pts diagnosed with PH, treated under the Polish ministry therapeutic program and registered in the national BNP-PL database, according to the intensity of specific PH therapy used in Poland. Methods We analyzed the records of the complete population of Polish pts treated under the National Drug Program of PH (PAH and CTEPH) and registered in the national database of BNP-PL from 01 March 2020 to 31 August 2022. The clinical severity of COVID-19 course and mortality were reviewed. Clinical characteristics of infected and deceased patients were compared in relation to the specific therapy used. Results The analysis included 188 pts with SARS-CoV-2 infection (mean age 59 ± 17,7 years; 61% female). 45 patients (24%) required hospitalization. Mortality rate was 18% (34/188, including 15 out-of-hospital deaths) vs. 2,6% for estimated in the general population. Those who died due to COVID-19 were slightly older (mean age 63 ± 18.4 vs. 58 ± 17.5 yrs; p=0,13). There was no significant difference in mortality in subsets receiving monotherapy (13.8%), 2 drugs (25.4%) or 3 drugs(15%)- p=0.18. There was a trend towards higher mortality in pts on double regimen. Pts treated with prostacyclin analogues had significantly higher risk of dying from COVID-19 (30% vs 11.4% in others, p=0.002). Conclusions COVID-19 infection in pulmonary hypertension pts was related to high mortality and prostacyclin analogues users are at highest risk. Considering that this analysis suggests that COVID-19 mortality was equalized between less sick patients suitable for monotherapy and those qualified for double/triple regimens. The finding of numerically highest risk in double therapy users might signify needs for earlier escalation to triple regimen.Characteristics of pts with PH and Covid

Clinical outcomes and genomic landscape of patients (pts) with EGFR-mutant lung cancer (EGFR+ LC) with central nervous system (CNS) metastases (mets).

e21146 Background: CNS mets are a major cause of morbidity and mortality in pts with LC. Up to 50% of pts with EGFR+ LC develop CNS mets over their disease course despite improvements in anti-EGFR therapies. The genomics alterations present in CNS mets in pts with EGFR+ LC and how these may compare to paired systemic samples has not been reported. Furthermore, it is unknown whether there are baseline clinicogenomic features that differ between EGFR+ LC pts with or without (w/wo) CNS mets. Methods: From an institutional database of LC pts with available next-generation sequencing (NGS) completed by MSK-IMPACT, we identified all EGFR+ LCs with molecularly characterized CNS tumor samples (CTS). We subsequently identified all pts with EGFR+ LCs with available paired CTS and systemic tumor samples (STS) profiled with MSK-IMPACT. All pts treated with 1L osimertinib with MSK-IMPACT available on their STS were also identified. We assessed clinicogenomic features of all selected EGFR+ LCs. Comparisons of frequencies of genes altered by somatic alterations were performed using Fisher’s exact test and logistic regression. Results: From 2014 to 2022, 90 EGFR+ LC pts with NGS performed on CTS were identified [brain metastasis (BrM), n = 38; leptomeningeal w/wo BrM (LM), n = 52]. 69 pts (77%) were female, median age 59 (IQR range:53-66 years), and 51 pts (57%) were never smokers. Patterns of EGFR+ were exon 19del (n = 43), L858R (n = 27) and atypical (n = 20). No genomic mutations were differentially altered in pts with LM vs BrM. Paired CTS and STS were available for 28 pts, where numerically higher rates of CDKN2A, CDKN2B loss and RAC1 amplification were seen in the CTS (respectively 43% vs 18%, 43% vs 18%, and 21% vs 0%, q > 0.05 for all). A total of 263 pts on 1L osi had NGS on their STS performed:136 pts (52%) had CNS mets during their disease course to date [94 pts (69%) de novo CNS mets; 42 pts with on-treatment CNS mets with median time to CNS mets of 25 mo (IQR: 13.5-35.3 mo)]. Between pts w/wo a lifetime history of CNS mets, there were no differences in sex, smoking history, EGFR alterations and co-alterations. CARD11 alterations were numerically higher in STS in pts with CNS mets (12% vs 2%, q > 0.05). Conclusions: In patients with EGFR+ LC, there were no genomic alterations that were significantly enriched in CNS mets compared to systemic disease, and no systemic genomic alterations that differentiate pts w/wo CNS mets.

Survivorship in patients with cardiac metastases defined by cardiac magnetic resonance imaging in relation to lesion hypoperfusion.

e24070 Background: Cardiac metastases (CMET) can occur in late-stage cancer, but limited data exists on prognostic implications in context of current day cancer care. Cardiac magnetic resonance imaging (CMR) provides a new, well validated, means to identify CMET in vivo, and assess magnitude of lesion vascularity – which can vary in relation to tumor etiology and be compromised with tumor necrosis. Survivorship in pts with CMET and modifying impact of lesion vascularity are unknown. Methods: The population comprised adult (≥18yo) pts with metastatic cancer derived from a dual site CMR registry, including pts with and without CMET on CMR. CMR was performed via a uniform protocol for which CMET was defined using established criteria as a cardiac mass with late gadolinium enhancement; lesion vascularity was measured on perfusion-CMR. Cancer type was categorized by pathological review and follow-up was performed for all-cause mortality. Results: 330 pts (59±15 yo; 55% M) were studied, inclusive of CMET and controls matched for cancer etiology/stage. Among pts with CMET, cancer etiology varied (sarcoma 24% | GI 18% | GU 13% | lymphoma 13% | lung 10% | skin/melanoma 7% |); cases and controls were similar with respect to age, sex, anti-cancer regimen, and cardiac function on CMR (all p = NS). Median duration of post-CMR follow-up was 19 months [IQR 11.9 – 43.6]; 92% had clinical follow-up ≥ 1 year or mortality within this interval, including an aggregate 1-year mortality in pts with CMET of 53% (43% in CMET - controls; p = 0.09). Among cancer categories, pts with lymphoma were at decreased risk for death (HR 0.44 [0.26 – 0.75], p = 0.002); risk was increased in pts with GI malignancies (1.63 [1.12 – 2.37], p = 0.01) or those treated with antimetabolites or kinase inhibitors (both p < 0.05): Neither age, sex, cardiac risk factors nor function granted increased risk for death (all p = NS). Regarding Cmet tissue characteristics, decreased lesion perfusion conferred increased mortality risk irrespective of whether assessed as a continuous variable (HR 1.29 [1.08 – 1.56]) or via graded tertiles (HR 1.32 [1.05 – 1.66]) of hypoperfusion (both p < 0.05). Decreased CMET perfusion conferred increased mortality risk (1.30 [1.03 – 1.64], p = 0.03) independent of cancer type or anticancer regimen. Conclusions: Among systemic cancer pts with CMET, survivorship varies and nearly half are alive ≥1 year post cardiac MRI diagnosis. Prognosis in pts with CMET varies inversely to lesion perfusion, with low vascularity lesions conferring increased mortality risk.[Table: see text]

In-hospital mortality analysis in patients with acute cardiovascular pathology and co-infection with COVID-19: a registry of one site

Abstract Funding Acknowledgements Type of funding sources: None. Patients with cardiovascular pathology have a significantly higher risk of adverse events and death when complicated by concomitant COVID-19. The aim of this study was to analyze in-hospital mortality in pts with acute cardiovascular pathology (ACP) and a co-infection with COVID-19. 139 pts with ACP who were diagnosed with COVID-19 were examined. 69 (49.6%) pts had ACS (47 pts with AMI), 33 (23.7%) pts - hypertensive urgency, 24 (17.3%) pts - ADHF, 9 (6.5%) pts - tachysystolic paroxysm of atrial fibrillation, 2 (1.4%) pts - acute pulmonary embolism, and 2 (1.4%) pts - syncope. The average age was 67.9±12.7 y.o., 70 (50.4%) pts were male. Concomitant arterial hypertension was found in 87.1%, DM – 20.9%, CHF - 30.9%, COPD – 9.4% of pts, history of AMI – 20.1% and ischemic stroke – 9.4% of pts. In 79 (56.8%) pts COVID-19 was diagnosed and laboratory confirmed before hospitalization (hospitalized in 5.3±3.6 days after symptoms onset). 31 (22.3%) pts were diagnosed with COVID-19 upon admission, and 29 (20.9%) - during their stay in the hospital. 20 (15.6%) pts were vaccinated against COVID-19. The initial SpO2 level was 91.6±10.3%, while more than half of pts (53.2%) had SpO2<95% and almost every fourth (23.2%) patient had SpO2<90%. During the hospital period, 20 (14.4%) pts died. The mortality rate was 28.0% in pts with ADHF, 19.1% in pts with AMI and significantly less in pts hospitalized for unstable angina, hypertensive urgency or atrial fibrillation - 5.2% (p<0.05 in comparison with pts with AMI or ADHF). The main cause of death was the development of cardiopulmonary failure – 14 (70.0%) pts. 4 (20.0%) pts died from AMI complications, 1 - from pulmonary embolism and 1 - from acute ischemic stroke. Two critical periods of in-hospital mortality can be distinguished: 1 - the first two days of hospitalization (mainly complications of acute cardiovascular pathology and thrombotic events); 2 – from 7 to 10 days after hospitalization (development of multiple organ failure due to hypoxia and heart failure progression). The mortality rate of patients with ACP and COVID-19 was significantly higher than that of simultaneously hospitalized patients without comorbid respiratory infection (14.4% vs. 6.4%, p=0.012) and patients who were hospitalized before the pandemic (14.4% vs. 2.9%, p<0.001). Vaccinated patients were significantly less likely to develop acute kidney injury, acute hypoxic delirium, had higher average blood spO2, and less often required non-invasive ventilation. Only 1 vaccinated patient died from the development of cardiogenic shock against the background of anterior AMI and multivessel coronary artery disease (mortality – 15.7% in unvaccinated pts vs 5.0% in vaccinated, p=0.076). Co-infection with COVID-19 worsens treatment outcomes and in-hospital mortality of patients with ACP. Vaccination significantly reduces the likelihood of complications and tends to reduce mortality.

Analysis of in-hospital complications in patients with acute cardiovascular pathology and co-infection with COVID-19: a registry of one center

The aim – to analyze in-hospital mortality in pts with acute cardiovascular pathology (ACP) and a co-infection with COVID-19.Materials and methods. 139 pts with ACP who were diagnosed with COVID-19 were examined. 69 (49.6 %) pts had ACS (47 pts with AMI), 33 (23.7 %) pts – hypertensive urgency, 24 (17.3 %) pts – ADHF, 9 (6.5 %) pts – tachysystolic paroxysm of atrial fibrillation, 2 (1.4 %) pts – acute pulmonary embolism, and 2 (1.4 %) pts – syncope. The average age was 67.9±12.7 y.o., 70 (50.4 %) pts were male. Concomitant arterial hypertension was found in 87.1 %, DM – 20.9 %, CHF – 30.9 %, COPD – 9.4 % of pts, history of AMI – 20.1 % and ischemic stroke – 9.4 % of pts. In 79 (56.8 %) pts COVID-19 was diagnosed and laboratory confirmed before hospitalization (hospitalized in 5.3±3.6 days after symptoms onset). 31 (22.3 %) pts were diagnosed with COVID-19 upon admission, and 29 (20.9 %) – during their stay in the hospital. 20 (15.6 %) pts were vaccinated against COVID-19. The initial SpO2 level was 91.6±10.3 %, while more than half of pts (53.2 %) had SpO2 < 95 % and almost every fourth (23.2 %) patient had SpO2 < 90 %.Results and discussion. During the hospital period, 20 (14.4 %) pts died. The mortality rate was 28.0 % in pts with ADHF, 19.1 % in pts with AMI and significantly less in pts hospitalized for unstable angina, hypertensive urgency or atrial fibrillation – 5.2 % (p<0.05 in comparison with pts with AMI or ADHF). The main cause of death was the development of cardiopulmonary failure – 14 (70.0 %) pts. 4 (20.0 %) pts died from AMI complications, 1 – from pulmonary embolism and 1 – from acute ischemic stroke. Two critical periods of in-hospital mortality can be distinguished: 1 – the first two days of hospitalization (mainly complications of acute cardiovascular pathology and thrombotic events); 2 – from 7 to 10 days after hospitalization (development of multiple organ failure due to hypoxia and heart failure progression). The mortality rate of patients with ACP and COVID-19 was significantly higher than that of simultaneously hospitalized patients without comorbid respiratory infection (14.4 % vs. 6.4 %, p=0.012) and patients who were hospitalized before the pandemic (14.4 % vs. 2.9 %, p<0.001). Vaccinated patients were significantly less likely to develop acute kidney injury, acute hypoxic delirium, had higher average blood SpO2, and less often required non-invasive ventilation. Only 1 vaccinated patient died from the development of cardiogenic shock against the background of anterior AMI and multivessel coronary artery disease (mortality – 15.7 % in unvaccinated pts vs 5.0 % in vaccinated, p=0.076).Conclusions. Co-infection with COVID-19 worsens treatment outcomes and in-hospital mortality of patients with ACP. Vaccination significantly reduces the likelihood of complications and tends to reduce mortality.

Utilization of Antifungal Prophylaxis and Treatment for Newly Diagnosed AML Patients Treated with Venetoclax Based Regimens in Routine Clinical Practice - a Prospective Analysis from the Revive Study

Background: Venetoclax (VEN)-based low intensity combinations are approved for the treatment of patients (pts) with acute myeloid leukemia (AML) ineligible for intensive chemotherapy. These combinations can be associated with prolonged cytopenias in particular neutropenia. Invasive fungal infections (IFIs) remain a major cause of morbidity and mortality in pts with AML but their incidence and impact on pts treated with VEN-based low intensity approach are uncertain. In the current study we assess real-world patterns of IFI's and antifungal treatments among newly-diagnosed (ND) AML patients treated with VEN-based low intensity therapies. Methods: The REVIVE study is a prospective, real-life, observational study that assesses patterns of pt. selection, efficacy and toxicity. ND pts with AML were enrolled at the time of VEN-based therapy initiation from 12 medical centers in Israel. Demographic, clinical and pt.-related baseline characteristics were documented. Antifungal medication selection for prophylaxis or therapy use and the incidence of IFIs were documented. The impact of prophylactic antifungal use on the incidence of IFIs and on leukemia related outcomes were assessed. Results: Between August 12, 2019, and April 15, 2022(data cut) ,189 AML pts were enrolled to receive VEN based therapy. Overall, the incidence of possible IFIs was relatively low and was observed in 17 patients (9% of patients). 23 pts (12.1%) were reported to have received prophylactic antifungal treatment, whereas 166 pts (87.8%) did not receive. Baseline characteristics of these two groups are shown in Table 1. Of note, pts. receiving antifungal prophylaxis were more likely to be treated as outpatients. A trend towards treatment in a tertiary center and unfavorable ELN risk was observed in pts. receiving antifungal prophylaxis vs. pts not receiving prophylaxis. All other characteristics seemed equally balanced between both groups. Antifungal prophylaxis included fluconazole (18 pts), voriconazole (6 pts) and posaconzole (1 pt). Of note, 2 patients received two different prophylactic treatments. The incidence of IFIs was not reduced in pts receiving antifungal prophylaxis. Of the 23 patients who received antifungal prophylaxis, 4 were considered to have an IFI (17.4%) compared with 13 in the non-prophylactic group (7.8%). Antifungal treatment in pts with an IFI included fluconazole (10pts) voriconazole (5 pts) posaconazole (1 pt) amphotericin B (1 pt) and anidulafungin (1pt). Of note, 3 patients received two different antifungal treatments. No difference in 30-day mortality was observed between the two groups:1 pt in the prophylaxis group died compared with 8 pts in the no-prophylaxis group (4.3% vs 4.8% respectively, p=0.92). Prophylactic antifungal treatment did not affect the rate of adverse events (AEs) leading to treatment discontinuation: 4 pts in the prophylaxis group and 31 pts in the no prophylaxis group discontinued VEN based treatment due to adverse events (17.4% vs 18.7%, p=0.88). The efficacy of VEN based treatment for AML was similar between pts who received or did not receive antifungal prophylaxis. Composite complete remission (CRc) rates were 60.9% in the antifungal prophylaxis group vs 54.2% in pts with no antifungal prophylaxis (p=0.54). A Kaplan-Meier analysis for overall survival (OS) showed no difference between the prophylaxis and no prophylaxis groups (p=0.505). 1year OS rates were: 50.6% (CI 28-73.3) and 39.4% (CI 30.5-48.3) for prophylaxis and no prophylaxis groups respectively. Median follow up in the prophylaxis group was 237 days (CI 56-878) compared with 173 days (CI 19-850) in the no-prophylaxis group. Conclusion: In this prospective 'real world' observational study, a low rate of IFIs were noted despite low utilization rates of antifungal prophylaxis, mostly with non-mold active azoles. Moreover, administration of antifungal prophylaxis was not associated with a reduced incidence of IFIs. Reassuringly, use of antifungal azoles as prophylactic treatment, which requires VEN dose adjustments, did not affect CRc and OS rates. Similarly, azole based prophylaxis did not affect for the rate of treatment discontinuation due to AEs or early mortality. This study does not support the routine use of antifungal prophylaxis and suggests that such treatment is safe if deemed necessary. Additional insights on antifungal treatment patterns and strategies are pending. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Clinical effectiveness of SARS-CoV-2 vaccines and booster doses in patients with cancer: An analysis from the European OnCovid registry.

e18725 Background: Immunogenicity and safety of SARS-CoV-2 vaccines have been widely investigated in patients (pts) with cancer. However, their effectiveness against Coronavirus disease 2019 (COVID-19) and the additional protective effect of a booster dose in this population are yet to be defined. Methods: Using OnCovid study data (NCT04393974), a European registry enrolling consecutive pts with cancer and COVID-19, we evaluated morbidity and 14 days case fatality rates (CFR14) from COVID-19 in pts who were unvaccinated, vaccinated (either partially/full vaccinated but not boosted) and those who had received a third dose. Analyses were restricted to pts diagnosed between 17/11/2021 (first breakthrough infection in a boosted pt) and the 31/01/2022. Pts with unknown vaccination status were excluded. Results: By the data lock of 22/02/2022, out of 3820 consecutive pts from 36 institutions, 415 pts from 3 countries (UK, Spain, Italy) were eligible for analysis. Among them, 51 (12.3%) were unvaccinated, 178 (42.9%) were vaccinated and 186 (44.8%) were boosted. Among vaccinated pts, 26 (14.6%) were partially vaccinated (1 dose). Pts with haematological malignancies had more likely received a booster dose prior to infection (25.4% vs 13.6% and 11.8%, p = 0.02). We found no other associations between vaccination status and pts’ characteristics including sex, age, comorbidities, smoking history, tumour stage, tumour status and receipt of systemic anticancer therapy. Compared to unvaccinated pts, boosted and vaccinated pts achieved improved CFR14 (6.8% and 7.0% vs 22.4%, p = 0.01), COVID-19-related hospitalization rates (26.1% and 20.6% vs 41.2%, p = 0.01) and COVID-19-related complications rates (14.5% and 15.7% vs 31.4%). Using multivariable Inverse Probability of Treatment Weighting (IPTW) models adjusted for sex, comorbidities, tumour status and country of origin we confirmed that boosted (OR 0.21, 95%CI: 0.05-0.89) and vaccinated pts (OR 0.19, 95%CI: 0.04-0.81) achieved improved CFR14 compared to unvaccinated pts, whilst a significantly reduced risk of COVID-19 complications (OR 0.26, 95%CI: 0.07-0.93) was reported for vaccinated pts only. Conclusions: SARS-CoV-2 vaccines protect from COVID-19 morbidity and mortality in pts with cancer. Accounting for the enrichment of haematologic pts in the boosted group, the observation of comparable mortality outcomes between boosted and vaccinated pts is reassuring and suggests boosting to be associated with reduced mortality in more vulnerable subjects, despite evidence of adverse features in this group.

Acute myeloid leukemia with KMT2Ar and association with risk of bleeding and early mortality.

7026 Background: Acute myeloid leukemia (AML) with rearrangement of KMT2A is characterized by chemotherapy resistance and high rates of relapse. However, additional causes of treatment failure or early mortality have not been well-defined in this entity. Methods: In a retrospective analysis, we compared causes and rates of early mortality following induction treatment between a cohort of adults with KMT2Ar AML (N=172) and an age-matched cohort of patients (pts) with normal karyotype (NK) AML (N=522). Results: The 30 and 60-day (60d) mortality in pts with KMT2Ar AML were significantly higher compared to those with NK AML, with rates of 10% (17/172 pts) and 15% (26/172 pts) in KMT2Ar AML vs 4% (20/522 pts) and 7% (38/522 pts) in NK AML, respectively ( P=0.004). Among those who died within 60d, the most common contributing cause in KMT2Ar was respiratory failure without a clear infectious etiology in 38% (10/26 pts) vs 11% (4/38 pts) in NK AML ( P=0.01). We found 42% (11/26 pts) with KMT2Ar AML who died within 60d were either diagnosed with or had high clinical suspicion for diffuse alveolar hemorrhage (DAH) that warranted empiric therapy vs 18% (7/38 pts) with NK AML ( P=0.05). Given the high occurrence of DAH in KMT2Ar AML, we set out to quantify bleeding events and recorded major and minor bleeds as defined by the International Society of Thrombosis and Haemostasis. We found 65% (17/26 pts) with KMT2Ar AML had at least one bleeding event vs 32% (12/38 pts) with NK AML ( P=0.01). There was a significantly higher frequent occurrence of major bleeds (rate ratio=6.22; P=0.005) and total bleeding events (rate ratio=4.5; P=0.001) in KMT2Ar AML vs NK AML. KMT2Ar was associated with disseminated intravascular coagulopathy (DIC), as 93% of evaluable pts (14/15 pts) vs 54% (7/13 pts) in NK AML had overt DIC before death. Longitudinal trajectories of DIC parameters of pts who died within 60d showed significantly higher prothrombin time levels ( P=0.008) in KMT2Ar. In a multivariate analysis, KMT2Ar and a monocytic phenotypic were the only independent predictors of any bleeding event in pts who died within 60d (OR 3.5, 95% CI 1.4-10.4, P=0.03; OR 3.2, 95% CI 1.1-9.4, P=0.04). Conclusions: KMT2Ar AML is associated with higher early mortality and an increased risk of bleeding and coagulopathy compared with NK AML. Early recognition and aggressive management of DIC and coagulopathy are important considerations that could mitigate the risk of death during induction treatment.[Table: see text]

710. Comparison of Initial CXR to CT in Patients (pts) with Hematologic Malignancy (HEM) and Documented Symptomatic Pulmonary Mucormycosis (PM)

BackgroundThere is a spectrum of pulmonary disease burden in pts with HEM and PM. There have not been any data comparing the sensitivity and findings of initial Chest X-Ray (CXR) and chest CT in these pts.MethodsWe compared the findings of the initial CXR and CT in all pts with proven or probable PM via EORTC/MSG criteria. We included only pts who had pulmonary symptoms and who had both CXR and CT within 5 days of each other and within seven days of symptom onset or date of culture at MD Anderson Cancer Center from April 2000 and April 2020. We collected data regarding demographics, status of HEM, clinical presentation, frequency and findings of BAL and imaging findings, mold-active prophylaxis and treatment regimens, and mortality. CXR findings were classified as normal or abnormal, and if abnormal sub-classified as mass-like/consolidative, nodular, cavitary or heterogenous/non-specific. CT findings were classified in a similar manner. ResultsWe Identified such 39 pts with PM who had both CXR and CT within 5 d. All pts had positive CT. Five pts (13%) had a negative CXR. The majority of pts 28 (72%) were neutropenic (neutrophil count < 500). The most common CXR findings were consolidation or mass-like lesions (56%), followed by patchy, heterogenous or non-specific findings (33%) and nodules (13%). Only 3% had cavitary lesions. Similarly, consolidation or mass-like lesions were the most common finding on CT (69%), followed by nodular lesions with or without ground glass halos (56%). Cavitary lesions and/or reverse halo sign (RHS) were common (31%) on CT. Patients with normal CXR vs those with abnormal CXR were comparable in all clinical parameters we collected. The median survival from time of symptoms onset for all pts was 45 days. There was a trend for lower 42 day mortality in pts with normal CXR (20% vs 47%, P=.253). ConclusionA negative CXR does not preclude PM, especially in neutropenic pts. A CT is recommended for better sensitivity and although there was concordance in CXR with CT findings in some chest abnormalities (mass, consolidation), CT more commonly revealed nodules and signs highly suggestive of PM such as RHS. Although small numbers precluded a robust comparison, it is possible that HEM pts with PM and negative initial CXR have better prognosis, perhaps reflecting a lower burden of pulmonary involvement Disclosures Dimitrios P. Kontoyiannis, MD, Astellas (Consultant)Cidara Therapeutics (Advisor or Review Panel member)Gilead Sciences (Consultant, Grant/Research Support, Other Financial or Material Support, Honoraria)

Abstract 13650: Prognostic Significance Of Atrial Arrhythmias In Pulmonary Hypertension: A Meta-analysis

Background: Atrial arrhythmias (AA: atrial tachycardia, atrial fibrillation, and atrial flutter) are common in patients (pts) with pulmonary hypertension (PH) due to increased right atrial pressure and increased sympathetic tone. AA occurrence in PH may lead to clinical deterioration and affect prognosis. Whether mortality in pts with PH is increased with comorbid AA compared to those without AA is not well established. The aim of this meta-analysis is to investigate published evidence of AA role in predicting outcomes of pts with PH. Methods and Results: We searched available literature across PubMed, EMBASE and Cochrane Library databases, and 11 observational studies with a pooled population of 2763 pts were included in this meta-analysis. Among the pooled population of pts with PH, there were 561 pts with AA (20%). We compared the outcomes of all-cause mortality among PH pts with and without AA. All-cause mortality was significantly higher in PH pts with AA compared to those without AA (odds ratio, OR=1.78; 95% confidence interval, 1.46-2.18; P &lt;0.01). No AA-driven differences were found among WHO groups of PH (p=0.75) or gender (p=0.42). Conclusion: Our results indicate that overall mortality is higher in PH pts presenting with AA as compared to those without AA. Further research needed in evaluating the effect of AA therapy with restoration and maintenance of sinus rhythm on mortality in PH.

COVID-19 in Patients with Chronic Myeloid Leukemia: Poor Outcomes for Patients with Comorbidities, Older Age, Advanced Phase Disease, and Those from Low-Income Countries: An Update of the Candid Study

COVID-19 in Patients with Chronic Myeloid Leukemia: Poor Outcomes for Patients with Comorbidities, Older Age, Advanced Phase Disease, and Those from Low-Income Countries: An Update of the Candid Study

Clinical Predictors of Outcome in Adult Patients with Acute Leukemias and Myelodysplastic Syndrome and COVID-19 Infection: Report from the American Society of Hematology Research Collaborative (ASH RC) Data Hub

Clinical Predictors of Outcome in Adult Patients with Acute Leukemias and Myelodysplastic Syndrome and COVID-19 Infection: Report from the American Society of Hematology Research Collaborative (ASH RC) Data Hub

A JAK2V617F Variant Allele Frequency Greater Than 50% Identifies Patients with Polycythemia Vera at High Risk for Venous Thrombosis

▪Background: Thrombosis is the main cause of morbidity and mortality in pts with Polycythemia Vera (PV). Current risk stratification is based on 2 variables: age >60y and history of thrombosis. Additional thrombotic risk factors in PV are generic cardiovascular risk factors and leukocytosis. JAK2V617F (JAK2VF) variant allele frequency (VAF) at diagnosis is highly heterogeneous. A VAF>75% was associated with higher rate of all thrombosis after diagnosis (Vannucchi AM et al, Leukemia 2007), and a VAF ≥ 60% correlated with increased rate of venous thrombosis (VT) in high-risk pts (Guglielmelli P et al, ASH 2018); however, predictive role of JAK2VF VAF is still debated.Aim: To evaluate the impact of JAK2VF VAF on rate of arterial and venous thrombosis in PV pts.Patients and methods: A cohort of 576 strictly 2016 WHO-defined PV pts followed at Univ. of Florence (1981-2020) were included. All pts were annotated for JAK2VF VAF, determined <3 years from diagnosis, and thrombosis at diagnosis and follow-up (FU). Arterial thromboses (AT) included stroke, transient ischemic attacks, retinal artery occlusion, coronary artery disease, and peripheral arterial disease; VT included cerebral venous thrombosis, deep vein thrombosis, pulmonary embolism. Splanchnic vein thromboses (SVT) were excluded. Only first occurring event was considered. Cox proportional hazard regression model was used for univariate and multivariable analysis. Kaplan-Meier (KM) analysis was used for time-to-event assessment, compared by log-rank test.Results: Median age was 61.4 y (range, 16.2-91.8), 58.2% were male; 62% were high-risk based on current classification. Median JAK2VF VAF was 41.5% (range, 0.3-100). A total of 76 (13.2%) pts had an AT event before/at PV diagnosis and 49 (8.5%) pts had an AT during FU. As regards VT, 64 (11.1%) and 39 (6.8%) pts had a VT before/at or after PV diagnosis, respectively. We found that JAK2 VAF as a continue variable was correlated with the risk of VT in FU (p=0.003) but not with AT (p=0.8). ROC analysis to determine the best cut-off level for JAK2 VAF predicting VT had an AUC of 0.72 and a best cut-off value of VAF=50%. VT at FU were significantly enriched in pts with VAF >50%: 14.5% versus 2.4%, p=<0.0001. VT -free survival (VT-FS) by KM was significantly shorter in the presence of a JAK2 VAF >50% (HR 4, CI 1.9-8.6, p<0.0001) (Figure 1A), whereas no difference was found for AT (HR 0.9). In addition to JAK2VF VAF>50%, univariate analysis for VT-FS identified history of VT (HR 2.9; CI 1.4-6.1, p=0.006), leukocytosis ≥11x10 9/L (HR 1.9; CI 1.1-3.4, p=0.02) and palpable splenomegaly (HR 1.9, CI 1-3.6; p=0.04) as risk factors. Multivariable analysis confirmed VAF>50% (HR 3.8, CI 1.8-8.1, p=0.0006) and previous VT (HR 2.4, CI 1.1-5.1; p=0.02) as independent risk factors for future VT. In contrast, univariate analysis for AT-free survival (AT-FS) identified history of AT (HR 2.5; CI 1.3-4.9, p=0.007), diabetes (HR 3.3; CI 1.6-6.5, p=0.0007), hyperlipidemia (HR 3.1; CI 1.7-5.6, p=0.0003) and hypertension (HR 2, CI 1.1-3.8; p=0.03) as predictors of future AT; age >60y showed only a trend (p=0.08). Multivariable analysis for AT-FS identified diabetes (HR 2.4, CI 1.2-5; p=0.02), hyperlipidemia (HR 2.3; CI 1.2-4.3, p=0.01) and previous AT (HR 2.1, CI 1-4.2; p=0.04) as independent predictors of future AT.Validation: Our findings were validated in an independent cohort of 315 2016-WHO defined PV pts from Policlinico Gemelli, Catholic Univ., Rome. After exclusion of 26 pts with SVT, analysis was conducted on 289 pts, 38 of them with thrombosis as heralding event (21 AT and 17 VT). Multivariable analysis confirmed JAK2VF VAF >50% (HR 2.3, CI 1.03-5.0, p=0.04) and previous VT (HR 4.5, CI 2.0-10.1; p=0.0003) as independent risk factors for future VT. In pts with VAF >50%, the rate of VT at FU was 19.9% vs 7.7%, P=0.005. KM curve showed that VT-FS was significantly shorter in pts with a JAK2VF VAF >50% (HR 2.2, CI 1.2-4.2; p=0.01) (Figure 1B). Of note, impact of JAK2 VAF>50% on VT at FU was statistically significant particularly in conventionally low-risk pts, accounting for an HR of 9.4 (CI 1.2-72) and HR 3.6 (CI 1.3-10) in Florence and Rome cohorts, respectively.Conclusions: These data support JAK2VF VAF as a strong independent predictor for future venous thrombosis in PV, in association with history of prior venous events, reinforcing that AT and VT are associated with unique risk factors in pts with PV.Supported by AIRC, Project Mynerva n.21267 [Display omitted] DisclosuresVannucchi: BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: 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; AbbVie: Membership on an entity's Board of Directors or advisory committees.

Modified CHA2DS2-VASc can predict mortality in COVID-19 patients admitted to the emergency department

IntroductionCHA2DS2-VASc score is used to determine the thromboembolic risk, but its prognostic value has been demonstrated in several cardiovascular (CV) diseases. Except for female gender, many CV risk factors comprising this score are recognized as risk factors for mortality in COVID-19. Cetinak G. et al demonstrated the ability of modified CHA2DS2-VASc (M-CHA2DS2-VASc) to predict mortality in COVID-19, which is based on changing gender criteria from female to male.PurposeTo evaluate the prognostic value of a M-CHA2DS2-VASc score to predict pulmonary embolism (PE) and mortality in pts with COVID-19 admitted at the emergency department (ED).MethodsRetrospective study of pts admitted to the ED between June 2020-January 2021, who underwent computed tomography pulmonary angiography (CTPA) due to PE suspicion. Pts were stratified into 3 M-CHA2DS2-VASc risk groups: lower (0–1), intermediate (2–3) and high risk (≥4). Kruskal-Wallis and X-square test were used to compare score risk groups. Logistic regression was used to determine predictors of PE and mortality. ROC curve was performed to evaluate the discriminative power of the score.ResultsWe included 300 pts: median age 71 years, 59% male. Hypertension (59%) chronic kidney disease (CKD, 33%), dyslipidemia (32%) and diabetes (28%) were the most common comorbidities. PE was diagnosed in 46 pts (15%). We found no difference in PE incidence according to M-CHA2DS2-VASc groups (p=0.531) and it showed no predictive value for PE (OR: 1.050, p=0.596). The AUC of M-CHA2DS2-VASc was 0.52, suggesting no discriminative power to predict PE.Regarding mortality, M-CHA2DS2-VASc score was higher in non-survivors COVID-19 pts than in survivors [4 (IQR 3–5) vs 2 (1–4), respectively, p<0.001]. A multivariate logistic regression analysis was performed for mortality based on M-CHA2DS2-VASC, troponin, CKD and smoking history, and only M-CHA2DS2-VASc was identified as an independent predictor of mortality (OR: 1.406, p=0.007). Kaplan-Meier showed that M-CHA2DS2-VASc score was associated with mortality: the survival rate was 92%, 80% and 63% in the lower, intermediate and higher M-CHA2DS2VASc score risk group (logrank test p<0.001; Fig. A).Most of the pts in the cohort were hospitalized (83%), but 21 pts (17%) discharged from the ED. Among these pts, 33% (n=17) had low risk, 37% (n=19) intermediate risk and 29% (n=15) high risk for mortality according to the M-CHA2DS2VASc score. The Kaplan-Meier individual survival analysis for hospitalized patients (Fig. B) and for those discharged from the ED (Fig. C) showed that M-CHA2DS2-VASc score had a good discriminative ability to predict short-term mortality for both groups (logrank test p<0.001 and p=0.007, respectively).ConclusionConsidering the lack of validated scores to predict mortality in COVID-19 pts, the M-CHA2DS2-VASc might be a simple tool to predict short-term mortality in these pts, irrespectively of the need for hospitalization or not.Funding AcknowledgementType of funding sources: None.

1590P Treatment outcomes and antibody immunity to SARS-CoV-2 in patients with hematological malignancies

Since SARS-CoV-2 infection heavily affects vulnerable populations including those with immune suppression, it is of special value to study clinical course, treatment outcomes, and immunity in patients (pts) with hematological (hem) malignancies. CHRONOS19 is an ongoing observational study in adult pts (≥18 years) with hem diseases (malignant or non-malignant) and COVID-19 in Russia. This web-based registry collected de-identified data from 15 centers all over the country at 30, 90, and 180 days after lab-confirmed or suspected (based on CT and/or clinical symptoms) COVID-19 diagnosis. The primary endpoint was 30-day all-cause mortality. As of data cut-off on April 14, 2021, 626 pts were enrolled in the study; 562 were eligible for primary endpoint assessment, n (%): M/F 271 (48%) / 291 (52%), median age 56 [18-90] years, malignant disease in 516 (92%) pts, among them induction phase / relapse or refractory / remission / NA in 180 (35%) / 120 (23%) / 187 (36%) / 29 (6%) pts. Thirty-day all-cause mortality in pts with hem malignancies was 19%; 83% of deaths were due to COVID-19 complications. No increase of hem disease relapse rate after COVID-19 was observed at Day 90 or Day 180, although 180-day data was still not mature at the time of analysis. IgG to SARS-CoV-2 was detected in 84% of pts with hem malignancies (167/199). The highest rate of detected antibody immunity was found in pts with chronic myeloproliferative neoplasms (100%; 13/13), HL (100%; 12/12), and multiple myeloma (97%; 34/35), the lowest – in pts with CLL (62%; 8/13) and NHL (60%; 6/10 and 56%; 10/18 for low-grade and high-grade lymphoma, respectively). igG detection rate in CD20+ lymphoma (60%) was significantly lower than in HL or T-cell lymphoma (p=0.004). Pts with ECOG 0-2 throughout the disease had a high rate of antibody immunity (90%; 104/116) vs. those with ECOG 3-4 at the time of COVID-19 diagnosis (77.5%; 31/40) or with worsening of ECOG to 3-4 during the disease (78%; 36/46). Five cases of SARS-CoV-2 re-infection were described. Pts with hem malignancies and COVID-19 have higher mortality than the general population. Low post-disease antibody immunity to SARS-CoV-2 and cases of re-infection may justify vaccination of these pts and warrant further research.

COVID-19 and hematologic diseases: Risk factors and long-term follow-up of CHRONOS19 Registry.

e18715 Background: Pts with hem diseases are at high risk of COVID-19 severe course and mortality. Emerging data on risk factors and outcomes in this patient population is of great value for developing strategies of medical care. Methods: CHRONOS19 is an ongoing nationwide observational cohort study of adult (≥18 y) pts with hem disease (both malignant and non-malignant) and lab-confirmed or suspected (clinical symptoms and/or CT) COVID-19. Primary objective was to evaluate treatment outcomes. Primary endpoint was 30-day all-cause mortality. Long-term follow-up was performed at 90 and 180 days. Data from 14 centers was collected on a web platform and managed in a deidentified manner. Results: As of data cutoff on January 27, 2021, 575 pts were included in the registry, 486 of them eligible for primary endpoint assessment, n(%): M/F 243(50%)/243(50%), median age 56 [18-90], malignant disease in 452(93%) pts, induction phase/R/R/remission 160(33%)/120(25%)/206(42%). MTA in 93(19%) pts, 158(33%) were transfusion dependent, comorbidities in 278(57%) pts. Complications in 335(69%) pts: pneumonia (67%), CRS (8%), ARDS (7%), sepsis (6%). One-third of pts had severe COVID-19, 25% were admitted to ICU, 20% required mechanical ventilation. All-cause mortality at 30 days – 17%; 80% due to COVID-19 complications. At 90 days, there were 14 new deaths: 6 (43%) due to hem disease progression. Risk factors significantly associated with OS are listed in Tab 1. In multivariate analysis – ICU+mechanical ventilation, HR, 53.3 (29.1-97.8). Acute leukemias were associated with higher risk of death, HR, 2.40 (1.28-4.51), less aggressive diseases (CML, CLL, MM, non-malignant) – with lower risk of death, HR, 0.54 (0.37-0.80). No association between time of COVID-19 diagnosis (Apr-Aug vs. Sep-Jan) and risk of death. COVID-19 affected treatment of hem disease in 65% of pts, 58% experienced treatment delay for a median of 4[1-10] weeks. Relapse rate on Day 30 and 90 – 4%, disease progression on Day 90 detected in 13(7%) pts; 180-day data was not mature at the time of analysis. Several cases of COVID-19 re-infection were described. Conclusions: Thirty-day all-cause mortality in pts with hem disease was higher than in general population with COVID-19. Longer-term follow-up (180 days) for hem disease outcomes and OS will be presented. [Table: see text]

Lower respiratory tract disease (LRTD) in patients with cancer and COVID-19: A COVID-19 and Cancer Consortium (CCC19) study.

6563 Background: Immunodeficiency in patients (pts) with cancer can lead to the progression of common respiratory viral infections to lower respiratory tract disease (LRTD) with potentially high mortality. Understanding risk factors of SARS-CoV-2 related LRTD in pts with cancer is imperative for the development of preventive measures. Methods: We examined all patients aged 18 years or older with cancer and laboratory-confirmed SARS-CoV-2 infection reported between March 16, 2020 and February 6, 2021 in the international CCC19 registry. We examined frequency of LRTD (pneumonia, pneumonitis, acute respiratory distress syndrome, or respiratory failure), demographic and clinicopathologic factors associated with LRTD, and 30-day and overall mortality in pts with and without LRTD. Results: Of 7,289 pts with a median follow-up time of 42 (21-90) days, 2187 (30%) developed LRTD. Pts of older age (65 yrs or older), male sex, pre-existing comorbidities, baseline immunosuppressants, baseline corticosteroids, and ECOG performance status of 2 or more had substantially higher rates of LRTD compared to those without these risk factors (Table). We did not observe differences in LRTD rates between pts of different racial/ethnic groups, smoking history, hypertension, obesity, cancer status, timing or type of anti-cancer therapy. LRTD was more likely in pts with thoracic malignancy (39%), hematological malignancy (39%) compared to those with other solid tumors (27%). The majority of pts (86%) had symptomatic presentation; however, 8% of pts with asymptomatic presentation developed LRTD. 30-day and overall mortality rates were significantly higher in pts with LRTD than those without LRTD (31% vs. 4% and 38% vs. 6%, P &lt; 0.05). Conclusions: COVID-19 related LRTD rate is high and associated with worse mortality rates in pts with cancer. The majority of risk factors associated with LRTD demonstrate underlying immunodeficiency or lung structural damage as a driving force in this population. Identifying pts at high-risk for developing LRTD can help guide clinical management, improve pt outcomes, increase the cost-effectiveness of antiviral therapy, and direct future clinical trial designs for vaccine or antiviral agents.[Table: see text]