ABSTRACT
INTRODUCTION: Patients (pts) with blood disorders are at particular risk for severe infection and death from COVID-19. Factors that contribute to this risk, including cancer treatment, have not been clearly delineated. The ASH RC COVID-19 Registry for Hematology is a public-facing, volunteer registry reporting outcomes of COVID-19 infection in pts with underlying blood disorders. We report a multivariable analysis of the impact of cancer treatment and other key variables on COVID-19 mortality and hospitalization among pts with blood cancer. METHODS: Data were collected between April 1, 2020, and July 2, 2021. All analyses were performed using R version 4.0.2. Multivariable logistic regression explored associations between mortality and seven patient/disease factors previously reported as important to COVID-19 outcome. Independent variables included: age (>60);sex;presence of a major comorbidity (defined as any of heart disease, hypertension, pulmonary disease and/or diabetes);type of hematologic malignancy;estimated prognosis of < 6 months prior to COVID-19;deferral of ICU care;and administration of cancer treatment in the previous year (excluding single agent hydroxyurea). A secondary multivariable logistic regression explored associations between the same variables and hospitalization with COVID-19. RESULTS: We included all pts in the registry with a malignant diagnosis except for 3 patients excluded based on a data sharing agreement (N=1029). Median age category was 50-59y (range <5y to > 90y). The sample was 42% female and 28% had major comorbidities. Types of hematologic malignancies were 354 (34%) acute leukemia/MDS, 255 (25%) lymphoma, 206 (20%) plasma cell dyscrasia (myeloma/amyloid/POEMS), 116 (11%) CLL, 98 (10%) myeloproliferative neoplasm (MPN). Most pts (73%) received cancer treatment during the previous year, 9% had a pre-COVID-19 prognosis of <6months, and 10% deferred ICU care. COVID-19 mortality in the entire cohort was 17%. In multivariable analyses, age > 60 (OR 2.03, 1.31-3.18), male sex (OR 1.69, 1.11 - 2.61), estimated pre-COVID-19 prognosis of less than 6 months (OR 6.16, 3.26 - 11.70) and ICU deferral (OR 10.87, 6.36 - 18.96) were all independently associated with an increased risk of death. Receiving cancer treatment in the year prior to COVID-19 diagnosis and type of hematologic malignancy were not significantly associated with death. In multivariable analyses, age > 60 (OR 2.46, 1.83 - 3.31), male sex (OR 1.34, 1.02 - 1.76), estimated pre-COVID-19 prognosis of < 6 months (OR 4.81, 2.45 - 10.50), presence of a major comorbidity (OR 1.57, 1.15 - 2.16), and cancer treatment in the previous year (OR 1.50, 1.10 - 2.06) were all independently associated with an increased risk of a severe COVID-19 requiring hospitalization. Pts with a MPN or plasma cell dyscrasia and COVID-19 were less likely to require hospitalization for COVID-19 compared to patients with CLL, leukemia/MDS, or lymphoma. CONCLUSIONS: These analyses confirm the negative impact of age > 60, male sex, pre-COVID-19 prognosis of < 6 months, and deferral of ICU care on mortality among patients with hematologic malignancy and COVID-19. We did not observe an increased risk of COVID-19 mortality among pts with COVID-19 who received blood cancer treatment in the previous year, although rate of hospitalization was higher. Pts with some hematologic malignancies (MPN, plasma cell dyscrasias), may experience less severe COVID-19 infections than others. Disclosures: Anderson: Celgene: Membership on an entity's Board of Directors or advisory committees;Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees;Gilead: Membership on an entity's Board of Directors or advisory committees;Janssen: Membership on an entity's Board of Directors or advisory committees;Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees;Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees;Pfizer: Membership on an entity's Board of Directors or advisory committees;Scientific Founder of Oncopep and C4 Therapeutics: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company;AstraZeneca: Membership on an entity's Board of Directors or advisory committees;Mana Therapeutics: Membership on an entity's Board of Directors or advisory committees. Desai: Janssen R&D: Research Funding;Astex: Research Funding;Kura Oncology: Consultancy;Agios: Consultancy;Bristol Myers Squibb: Consultancy;Takeda: Consultancy. Goldberg: Celularity: Research Funding;Genentech: 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;Aptose: Consultancy, Research Funding;Prelude Therapeutics: Research Funding;DAVA Oncology: Honoraria;Pfizer: Research Funding;Arog: Research Funding;Aprea: Research Funding;AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Neuberg: Madrigal Pharmaceuticals: Other: Stock ownership;Pharmacyclics: Research Funding. Radhakrishnan: Janssen India: Honoraria;Dr Reddy's Laboratories: Honoraria, Membership on an entity's Board of Directors or advisory committees;Aurigene: Speakers Bureau;Novartis: Honoraria;Johnson and Johnson: Honoraria;Pfizer: Consultancy, Honoraria;Astrazeneca: Consultancy, Honoraria;Emcure Pharmaceuticals: Other: payment to institute;Cipla Pharmaceuticals: Honoraria, Other: payment to institute;Bristol Myers Squibb: Other: payment to institute;Roche: Honoraria, Other: payment to institute;Intas Pharmaceutical: Other: payment to institute;NATCO Pharmaceuticals: Research Funding. Sehn: Genmab: Consultancy;Debiopharm: Consultancy;Novartis: Consultancy. Sekeres: Novartis: Membership on an entity's Board of Directors or advisory committees;Takeda/Millenium: Membership on an entity's Board of Directors or advisory committees;BMS: Membership on an entity's Board of Directors or advisory committees. Tallman: Kura: Membership on an entity's Board of Directors or advisory committees;Syros: Membership on an entity's Board of Directors or advisory committees;Innate Pharma: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;Biosight: Membership on an entity's Board of Directors or advisory committees;Roche: Membership on an entity's Board of Directors or advisory committees;Jazz Pharma: Membership on an entity's Board of Directors or advisory committees;Oncolyze: Membership on an entity's Board of Directors or advisory committees;KAHR: Membership on an entity's Board of Directors or advisory committees;Orsenix: Membership on an entity's Board of Directors or advisory committees;Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees;Abbvie: Membership on an entity's Board of Directors or advisory committees;Amgen: Research Funding;Rafael Pharmaceuticals: Research Funding;Glycomimetics: Research Funding;Biosight: Research Funding;Orsenix: Research Funding;Abbvie: Research Funding;NYU Grand Rounds: Honoraria;Mayo Clinic: Honoraria;UC DAVIS: Honoraria;Northwell Grand Rounds: Honoraria;NYU Grand Rounds: Honoraria;Danbury Hospital Tumor Board: Honoraria;Acute Leukemia Forum: Honoraria;Miami Leukemia Symposium: Honoraria;New Orleans Cancer Symposium: Honoraria;ASH: Honoraria;NCCN: Honoraria.
ABSTRACT
Background: Predictors of severe infection and outcomes with COVID-19 in patients (pts) with acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and myelodysplastic syndromes (MDS) are lacking. Pts with active disease may experience worse outcomes due to overall prognosis and cytopenias. Here we identify risk factors for severe COVID-19 infection and mortality in pts with AML, MDS, and ALL using the ASH RC COVID-19 Registry for Hematology. Methods: The ASH RC COVID-19 Registry for Hematology includes features and outcomes of a laboratory-confirmed or presumptive diagnosis of SARS-CoV-2 infection in adult pts with ongoing or a history of blood disorders. The Registry opened for data collection on April 1, 2020 and is a global effort housed on a secure data platform hosted by Prometheus Research, an IQVIA company. Data are made publicly available and regularly updated on the ASH RC website. Pt characteristics, outcomes, and predictors were analyzed and stratified by disease status (active initial diagnosis and relapsed/refractory vs. remission) and type of hematologic malignancy. Variables included age, comorbidities, type of hematologic malignancy (AML, MDS, ALL), neutrophil and lymphocyte count at time of COVID-19 diagnosis, and active treatment at the time of COVID-19 diagnosis. COVID-19 severity was defined as mild (no hospitalization required), moderate (hospitalization required), or severe (ICU admission required). Categorical pt characteristics for each response group and associations between response groups and characteristics (i.e., alive vs. dead, severity vs. non-severity) were summarized by frequency with differences between response groups evaluated by Fisher's exact test and odds ratios with 95% confidence intervals (CIs) estimated by logistic regression. Multivariable analyses identified independent predictors of outcomes. Results: Analyses were conducted on data from 257 pts with AML (n=135), MDS (n=40), and ALL (n=82);46% were in remission and 44% had active disease (10% unknown). Overall mortality from COVID-19 infection was 21%. Pts with active disease were significantly more likely to present with moderate and severe COVID-19 compared to those in remission (remission vs. active disease, severe 33% (n=20) vs. 67%(n=40), moderate 45% (n=35) vs.55% (n=42), and mild: 67% (n=56) vs. 33% (n=28), p value <0.001) (Figure 1). This was significant when categorized as severe vs. non severe as well (p=0.002). COVID-19 severity was also associated with AML diagnosis, major comorbidities, and neutropenia and lymphopenia at the time of COVID-19 diagnosis. Univariate analyses of increased mortality after COVID-19 diagnosis were significantly associated with advanced age, male sex, pre-diagnosis survival < 6 months, active disease status, neutropenia, lymphopenia and forgoing ICU care. Multivariable analyses in all pts (Figure 1), revealed that increased COVID-19 related mortality was significantly associated with neutropenia at diagnosis (OR 3.15, 95% C.I. 1.31-8.08, p=0.01), estimated pre-COVID-19 prognosis of < 6 months (OR 8.58, 95% C.I. 3.24-24.46, p<0.001) and forgoing ICU care (OR 6.66, 95% C.I. 2.56-18.23, p<0.001). Among hospitalized pts, increased COVID-19 mortality was associated with estimated pre-COVID-19 prognosis of < 6 months (OR 6.77, 95% C.I. 2.34-22.24, p<0.001) and forgoing ICU care (OR 3.98, 95% C.I. 1.45-11.66, p=0.007). Pts who were older, male, smokers, with active disease, or estimated to have pre-COVID-19 survival of < 6 months were more likely to forgo ICU care. Forgoing ICU care (n=37,16%) was associated with a higher COVID-19 mortality in all pts (n=234, OR 15.6, 95% C.I. 6.4-40.9, p<0.001), hospitalized pts (n=143, OR 9.2, 95% C.I., 3.5-26.5, p<0.001) and in pts where ICU admission was indicated and declined (n=61 OR 5.6, 95% C.I. 1.1-56.4, p=0.03)). Neither active disease status nor ongoing cancer treatment were associated with increased mortality among hospitalized patients. Conclusions: These data suggest that patients with active disease experience significantly higher COVID-19 severity but not increased mortality from COVID-19. Patients who had neutropenia and a pre-COVID-19 prognosis of < 6 months had higher mortality from COVID-19 infection and may be more likely to forgo ICU care. If desired by patients, aggressive support for hospitalized patients with COVID-19 is appropriate regardless of remission status. [Formula presented] Disclosures: Desai: Agios: Consultancy;Janssen R&D: Research Funding;Kura Oncology: Consultancy;Bristol Myers Squibb: Consultancy;Astex: Research Funding;Takeda: Consultancy. Goldberg: AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Aprea: Research Funding;Prelude Therapeutics: Research Funding;Pfizer: Research Funding;Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees;DAVA Oncology: Honoraria;Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees;Arog: Research Funding;Celularity: Research Funding;Aptose: Consultancy, Research Funding. Anderson: Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees;Celgene: Membership on an entity's Board of Directors or advisory committees;Gilead: Membership on an entity's Board of Directors or advisory committees;Janssen: Membership on an entity's Board of Directors or advisory committees;Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees;Pfizer: Membership on an entity's Board of Directors or advisory committees;Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees;Scientific Founder of Oncopep and C4 Therapeutics: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company;AstraZeneca: Membership on an entity's Board of Directors or advisory committees;Mana Therapeutics: Membership on an entity's Board of Directors or advisory committees. Neuberg: Pharmacyclics: Research Funding;Madrigal Pharmaceuticals: Other: Stock ownership. Radhakrishnan: Emcure Pharmaceuticals: Other: payment to institute;Bristol Myers Squibb: Other: payment to institute;Astrazeneca: Consultancy, Honoraria;Cipla Pharmaceuticals: Honoraria, Other: payment to institute;Pfizer: Consultancy, Honoraria;Johnson and Johnson: Honoraria;Novartis: Honoraria;Aurigene: Speakers Bureau;Roche: Honoraria, Other: payment to institute;Intas Pharmaceutical: Other: payment to institute;Dr Reddy's Laboratories: Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen India: Honoraria;NATCO Pharmaceuticals: Research Funding. Roboz: Novartis: Consultancy;Mesoblast: Consultancy;Amgen: Consultancy;Actinium: Consultancy;AbbVie: Consultancy;Janssen: Consultancy;Blueprint Medicines: Consultancy;Astex: Consultancy;Janssen: Research Funding;Daiichi Sankyo: Consultancy;Jazz: Consultancy;Agios: Consultancy;Glaxo SmithKline: Consultancy;Celgene: Consultancy;Otsuka: Consultancy;Astellas: Consultancy;Helsinn: Consultancy;MEI Pharma - IDMC Chair: Consultancy;Jasper Therapeutics: Consultancy;Bristol Myers Squibb: Consultancy;AstraZeneca: Consultancy;Bayer: Consultancy;Pfizer: Consultancy;Roche/Genentech: Consultancy. Sehn: Novartis: Consultancy;Genmab: Consultancy;Debiopharm: Consultancy. Sekeres: Takeda/Millenium: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;BMS: Membership on an entity's Board of Directors or advisory committees. Tallman: Syros: Membership on an entity's Board of Directors or advisory committees;Kura: Membership on an entity's Board of Directors or advisory committees;NYU Grand Rounds: Honoraria;Innate Pharma: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;Biosight: Membership on an entity's Board of Directors or advisory committees;Roche: Membership on an entity's Board of Directors or advisory committees;Jazz Pharma: Membership on an entity's Board of Directors or advisory committees;Oncolyze: Membership on an entity's Board of Directors or advisory committees;KAHR: Membership on an entity's Board of Directors or advisory committees;Orsenix: Membership on an entity's Board of Directors or advisory committees;Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees;Abbvie: Membership on an entity's Board of Directors or advisory committees;Amgen: Research Funding;Rafael Pharmaceuticals: Research Funding;Glycomimetics: Research Funding;Biosight: Research Funding;Orsenix: Research Funding;Abbvie: Research Funding;Mayo Clinic: Honoraria;UC DAVIS: Honoraria;Northwell Grand Rounds: Honoraria;NYU Grand Rounds: Honoraria;Danbury Hospital Tumor Board: Honoraria;Acute Leukemia Forum: Honoraria;Miami Leukemia Symposium: Honoraria;New Orleans Cancer Symposium: Honoraria;ASH: Honoraria;NCCN: Honoraria. Wood: Pfizer: Research Funding;Teladoc: Consultancy;Koneksa Health: Consultancy, Current equity holder in publicly-traded company.
ABSTRACT
The rapid emergence of coronavirus disease 2019 (COVID-19) as a global pandemic affecting millions of individuals globally has necessitated sensitive and high-throughput approaches for the diagnosis, surveillance, and determining the genetic epidemiology of SARS-CoV-2. In the present study, we used the COVIDSeq protocol, which involves multiplex-PCR, barcoding, and sequencing of samples for high-throughput detection and deciphering the genetic epidemiology of SARS-CoV-2. We used the approach on 752 clinical samples in duplicates, amounting to a total of 1536 samples which could be sequenced on a single S4 sequencing flow cell on NovaSeq 6000. Our analysis suggests a high concordance between technical duplicates and a high concordance of detection of SARS-CoV-2 between the COVIDSeq as well as RT-PCR approaches. An in-depth analysis revealed a total of six samples in which COVIDSeq detected SARS-CoV-2 in high confidence which were negative in RT-PCR. Additionally, the assay could detect SARS-CoV-2 in 21 samples and 16 samples which were classified inconclusive and pan-sarbeco positive respectively suggesting that COVIDSeq could be used as a confirmatory test. The sequencing approach also enabled insights into the evolution and genetic epidemiology of the SARS-CoV-2 samples. The samples were classified into a total of 3 clades. This study reports two lineages B.1.112 and B.1.99 for the first time in India. This study also revealed 1,143 unique single nucleotide variants and added a total of 73 novel variants identified for the first time. To the best of our knowledge, this is the first report of the COVIDSeq approach for detection and genetic epidemiology of SARS-CoV-2. Our analysis suggests that COVIDSeq could be a potential high sensitivity assay for the detection of SARS-CoV-2, with an additional advantage of enabling the genetic epidemiology of SARS-CoV-2.