COVID-19 in patients with gynecologic cancer: A preliminary report from the COVID-19 and Cancer Consortium (CCC19)

Background: Limited information exists regarding the severity of short-term outcomes among patients with gynecologic cancer who are infected with SARS-CoV-2. Methods: Patients with gynecologic cancer and laboratory confirmed SARS-CoV-2 infection were identified from the international CCC19 registry. We estimated odds ratios (OR) from ordinal logistic regression for associations with severity of COVID-19 outcomes, defined from least to most severe as hospitalization, intensive care unit (ICU) admittance, mechanical ventilation, and 30-day mortality. Results: Of 842 patients identified, 48% had endometrial cancer, 24% had ovarian cancer, 22% had cervical cancer, and 6% had dual primary/other gynecologic cancers. The majority were from the United States (86%), most were non-Hispanic White (46%), and the median age was 62 years (IQR 52-72). The majority were diagnosed with localized disease (68%);only 18 (2%) and 15 (2%) were fully or partially vaccinated, respectively. In the 3 months prior to COVID-19, 36% had any cancer treatment, with chemotherapy the most common (23%). When diagnosed with COVID-19, most patients were in remission (50%), while 37% had active disease, including 22% with metastatic disease. Most patients presented with typical COVID-19 symptoms (76%);few had a poor ECOG performance status (PS ≥2, 14%). Outcomes included hospitalization (50%), ICU admittance (12%), mechanical ventilation (8%), and death within 30 days of testing positive for SARS-CoV-2 (10%). In unadjusted models, increasing age (OR: 1.03 1.02-1.04) and Black race (OR 1.91, 1.31-2.77) were associated with increased severity of COVID-19 outcomes. Compared to patients in remission for ≥5 years, those with progressive disease had increased severity (OR 1.88, 1.25-2.82), while those in remission for < 5 years or with stable disease had decreased severity of COVID-19 outcomes (OR 0.55, 0.39-0.76). In multivariable models that included adjustment for age, race, and cancer status, additional factors associated with increased COVID-19 outcome severity included cardiac (OR 1.57, 1.13-2.19) and renal (OR 2.00, 1.33-3.00) comorbidities, an ECOG PS ≥2 (OR 5.15, 3.21-8.27), having pneumonia or pneumonitis (OR 4.08, 2.94-5.66), venous thromboembolism (OR 4.67, 2.49-8.75), sepsis (OR 14.2, 9.05-22.1), or a co-infection within ±2 weeks of SARS-CoV-2 (OR: 4.40, 2.91-6.65);asymptomatic SARS-CoV-2 infection was associated with decreased severity of outcomes (OR: 0.25, 0.16-0.38). The overall case fatality rate was 15.7%. Conclusions: Patients with gynecologic cancer experience significant morbidity and mortality related to infection with SARS-CoV-2. Age, race, cancer status, co-morbidities, and COVID-19 complications were associated with more severe COVID-19 outcomes, along the continuum from least to most, of hospitalization, ICU admittance, mechanical ventilation, and 30-day mortality.

Bleeding Complications in Patients with Cancer and COVID 19- Analysis from the COVID 19and Cancer Consortium (CCC19) Registry

Background : Patients (pts) with COVID-19 are reported to have increased risk of venous thromboembolism yet bleeding has been an under recognized complication. Rates of bleeding remain unexamined in all patients especially in pts with cancer and COVID-19. Aim: To estimate the incidence of bleeding complication in patients with cancer and COVID 19 Methods: The CCC19 international registry (NCT04354701) aims to investigate complications of COVID-19 in pts with cancer. Our aim was to investigate the frequency of bleeding in hospitalized adult pts with cancer andCOVID-19, enrolled between March 16, 2020 and Feb 8, 2021. The incidence of bleeding complications was captured as defined by CCC19 and included both major and non major bleeding. Associated baseline clinic-pathologic prognostic factors and outcomes such as need for mechanical ventilation, intensive care unit (ICU) admission and mortality rates were assessed Results :3849 pts met analysis inclusion criteria. Bleeding was reported in 276 (7%) pts with median age of 70years;incidence was 6.6 % in females and 7.6 % in males, 6.5% in non-Hispanic white pts, 8.2 % in non-Hispanic Black pts, and 7.8 % in Hispanic pts. 74% had solid cancer and 29% had hematologic malignancies, 33% had received anti-cancer therapy in preceding 30 days, and 8% had surgery within 4weeks. In pts taking antiplatelet or anticoagulant medications at baseline, 7.2% developed bleeding. Need for mechanical ventilation, ICU admission, 30-day mortality, and total mortality were significantly higher in those with bleeding complications compared to those without, p<0.05 Conclusion : We describe the incidence of bleeding in a large cohort of pts with cancer and COVID-19. Bleeding events were observed in those with adverse outcomes including mechanical ventilation, ICU admission, and high mortality;the overall mortality of 43% in patients with bleeding complications is especially notable. This important complication may reflect underlying COVID-19 pathophysiology as well as iatrogenic causes. [Formula presented] Disclosures: Kumar: Diagnostica Stago: Honoraria. Zon: AMAGMA AND RLZ: Consultancy, Current holder of individual stocks in a privately-held company. Byeff: Pfizer, BMS, Takeda,Teva, Merck, United health: Consultancy, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company. Nagaraj: Novartis: Research Funding. Hwang: astrazaneca,Merck,bayer, Genentech: Consultancy, Research Funding. McKay: Myovant: Consultancy;Bayer: Membership on an entity's Board of Directors or advisory committees;AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees;Exelixis: Consultancy, Membership on an entity's Board of Directors or advisory committees;Calithera: Membership on an entity's Board of Directors or advisory committees;Tempus: Research Funding;Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees;Tempus: Membership on an entity's Board of Directors or advisory committees;Pfizer: 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;Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees;Sanofi: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;Dendreon: Consultancy;Caris: Other: Serves as a molecular tumor board;Vividion: Consultancy;Sorrento Therapeutics: Consultancy;Bayer: Research Funding. Warner: Westat, Hemonc.org: Consultancy, Current holder of stock options in a privately-held company. Connors: Pfizer: Honoraria;CSL Behring: Research Funding;Alnylam: Consultancy;Bristol-Myers Squibb: Honoraria;takeda: Honoraria;Abbott: Consultancy. Rosovsky: Janssen: Consultancy, Research Funding;BMS: Consultancy, Research Funding;Inari: Consultancy, Membership on an entity's Board of Directors or advisory committees;Do a: Consultancy, Membership on an entity's Board of Directors or advisory committees.

COVID-19 vaccination and breakthrough infections in patients with cancer.

BACKGROUND: Vaccination is an important preventive health measure to protect against symptomatic and severe COVID-19. Impaired immunity secondary to an underlying malignancy or recent receipt of antineoplastic systemic therapies can result in less robust antibody titers following vaccination and possible risk of breakthrough infection. As clinical trials evaluating COVID-19 vaccines largely excluded patients with a history of cancer and those on active immunosuppression (including chemotherapy), limited evidence is available to inform the clinical efficacy of COVID-19 vaccination across the spectrum of patients with cancer. PATIENTS AND METHODS: We describe the clinical features of patients with cancer who developed symptomatic COVID-19 following vaccination and compare weighted outcomes with those of contemporary unvaccinated patients, after adjustment for confounders, using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19). RESULTS: Patients with cancer who develop COVID-19 following vaccination have substantial comorbidities and can present with severe and even lethal infection. Patients harboring hematologic malignancies are over-represented among vaccinated patients with cancer who develop symptomatic COVID-19. CONCLUSIONS: Vaccination against COVID-19 remains an essential strategy in protecting vulnerable populations, including patients with cancer. Patients with cancer who develop breakthrough infection despite full vaccination, however, remain at risk of severe outcomes. A multilayered public health mitigation approach that includes vaccination of close contacts, boosters, social distancing, and mask-wearing should be continued for the foreseeable future.

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

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 < 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 Presented).

Concomitant infections in patients with cancer and COVID-19: A COVID-19 and Cancer Consortium (CCC19) study

Background: COVID-19 has been associated with immune modulation that may predispose infected patients to bacterial, viral, or fungal coinfections. Due to critical illness, > 70% of patients with severe COVID-19 receive empiric antibacterial or antifungal therapy, along with standard anti-COVID-19 treatments. However, the frequency of proven or probable secondary infections is < 10%. To our knowledge, there are no studies evaluating co-infections in patients with cancer and COVID-19, a vulnerable group with multiple risk factors for co-infections. We aim to describe the prevalence of bacterial, viral, and fungal co-infections, identify risk factors for coinfection, and investigate the potential impact of co-infections on mortality, in patients with a history of cancer and COVID-19. Methods: The CCC19 registry (NCT04354701) includes patients with active or prior hematologic or invasive solid malignancies reported across academic and community sites. We captured bacterial, fungal, or viral coinfections diagnosed within ±2 weeks from diagnosis of COVID-19, identified factors associated with an increased risk of having a coinfection, and evaluated the association of coinfections with 30-day all-cause mortality. Results: We examined 6732 patients with a history of cancer and a laboratory-confirmed diagnosis of SARS-CoV-2 reported to CCC19 by 82 sites between March 17, 2020 and February 3, 2021, with complete data on coinfection status. Median age was 65 (interquartile range: 55-75) years with 48% male, 52% non-Hispanic white, 19% non-Hispanic black, and 16% Hispanic. 5448 (81%) had solid tumors and 1466 (22%) had hematologic malignancies. Bacterial infections were reported in 823 patients (12%), including 296 Gram+ and 245 Gram- bacterial events. Documented viral (176 patients, 3%) and fungal (59 patients, 0.9%) co-infections were rare. The risk for co-infections increased with age, and they were more frequent among men, older patients, and those with diabetes, pulmonary or renal comorbid conditions, active progressive cancer, or hematologic malignancies (unadjusted P< 0.01). The frequency of reported co-infections decreased over the study period (divided into quartiles, Mantel-Haenszel P< 0.01). All-cause mortality rates were higher among those with bacterial (24% vs. 10%), viral (22% vs. 12%), and fungal (37% vs. 12%) coinfections compared to those without (unadjusted P< 0.01). Conclusions: The frequency of bacterial infections in patients with cancer and COVID-19 is relatively low. Viral and fungal co-infections are uncommon. Coinfections are associated with higher mortality rates. Several patient and tumor factors can be used for risk stratification and guide early empiric antimicrobial agent selection, which may improve clinical outcomes. These data could inform antimicrobial stewardship interventions in this tenuous patient population.

Racial and ethnic disparities among patients with breast cancer and COVID-19

Background: Racial/ethnic minorities have disproportionately increased risk of contracting COVID-19 and experiencing severe illness;they also have worse breast cancer (BC) outcomes. COVID-19 outcomes among racial/ethnic minorities with BC are currently unknown. We sought to compare clinicopathologic characteristics and COVID-19 outcomes stratified by race/ethnicity. Methods: The COVID-19 and Cancer Consortium registry (NCT04354701) was used to identify patients with invasive BC and laboratory-confirmed SARS-CoV-2 diagnosed in the U.S. between 2020-03-06 and 2021-02-04. The primary analysis was restricted to women who selfidentified as non-Hispanic White (NHW), nonHispanic Black (NHB), or Hispanic (H). Demographic, cancer characteristics, and COVID-19 outcomes were evaluated. COVID-19 outcomes included: hospital admission, intensive care unit (ICU) admission, mechanical ventilation, death within 30 days of COVID-19 diagnosis and death from any cause during follow-up. Descriptive statistics were used to compare clinicopathologic characteristics and Fisher exact tests were used to compare COVID19 outcomes across the 3 racial/ethnic groups. Results: A total of 1133 patients were identified of which 1111 (98%) were women;of which 575 (52%) NHW, 243 (22%) NHB, 183 (16%) H, and 110 (10%) other/unknown. Baseline characteristics differed among racial/ethnic groups. H were younger (median age: NHW 63y;NHB 62y;H 54y) and more likely to be never smokers (NHW 62%;NHB 62%;H 78%). NHB had higher rates of obesity (NHW 40%;NHB 54%;H 46%), diabetes (NHW 16 %;NHB 32%;H 20%) and combined moderate and severe baseline COVID-19 at presentation (NHW 28%;NHB 42%;H 28%). Cancer characteristics are as shown (Table). Significant differences were observed in outcomes across racial/ethnic groups including higher rates of hospital admission (NHW 34%;NHB 49%;H 34%;P <0.001), mechanical ventilation (NHW 3%;NHB 9%;H 5%;P=0.002), 30-day mortality (NHW 6%;NHB 9%;H 4%;P=0.043) and total mortality (NHW 8%;NHB 12%;H 5%;P=0.05) among NHB compared to NHW and H. Conclusions: This is the largest study to show significant differences in COVID-19 outcomes by racial/ethnic groups of women with BC. The adverse outcomes in NHB could be due to higher moderate to severe COVID-19 at presentation and preexisting comorbidities. H did not have worse outcomes despite having more active disease and recent anti-cancer therapy, including with cytotoxic chemotherapy - potentially due to younger age and nonsmoking status. (Table Presented).