Smoking and COVID-19 in patients with cancer: Novel analysis from CCC19 registry

Background: Patients (pts) with thoracic cancers have a high rate of hospitalization and death from COVID-19. Smoking has been associated with increased risk for severe COVID-19. However, there is limited data evaluating the impact of smoking recency on COVID-19 severity in pts with cancer. We aimed to characterize the clinical outcomes of COVID-19 based on the recency of smoking in pts with thoracic cancers (TC) and all other cancers (OC). Methods: Adult pts with cancer and lab-confirmed SARS-CoV-2 and smoking history recorded in the CCC19 registry (NCT0435470) were included. Pts were stratified by cancer type (TC or OC) and further stratified into subgroups based on the recency of smoking cessation: current smoker;former smokers who quit < 1 yr. ago;1-5 yr. ago;6-10 yr. ago;quit > 10 yr. ago;and never smoker. 30-day all-cause mortality was the primary endpoint. Secondary endpoints were any hospitalization;hospitalization with supplemental O2;ICU admission;and mechanical ventilation. Results: From January 2020 to December 2021, 752 pts from TC group and 8,291 pts from OC group met the inclusion criteria. 78% of patients in TC group ever smoked compared to 36% patients in the OC group. In both groups, the majority of never-smokers were females (70% and 60% in TC and OC respectively). The burden of smoking and the rate of pulmonary comorbidities (PC) was higher in the TC group (PC 22-69%) compared to OC group (PC 12-26%) across all smoking strata. Overall, 30-day all-cause mortality was 21% and 11% in pts with TC and OC respectively. Former smokers who quit < 1 year ago in TC group had the highest rate of mortality and severe COVID-19 outcomes. However, in the OC group, there was no consistent trend of higher mortality or severe COVID-19 outcomes in specific subgroups based on smoking recency. Conclusions: To our knowledge this is the largest study evaluating the effect of granular phenotypes of smoking recency on COVID-19 outcomes in pts with cancer. Recent smokers who quit < 1 year ago in TC group had the highest rate of mortality and severe COVID-19. Further analysis exploring the factors (e.g., smoking pack years) associated with severe outcomes in this subgroup is planned.

Post-acute sequelae of SARS-CoV-2 infection in patients with cancer

Background: Most patients with cancer and COVID-19 will survive the acute illness. The longer-term impacts of COVID-19 on patients with cancer remain incompletely described. Methods: Using COVID-19 and Cancer Consortium registry data thru 12/31/2021, we examined outcomes of long-term COVID-19 survivors with post-acute sequelae of SARS-CoV-2 infection (PASC aka “long COVID”). PASC was defined as having recovered w/ complications or having died w/ ongoing infection 90+ days from original diagnosis;absence of PASC was defined as having fully recovered by 90 days, with 90+ days of follow-up. Patients with SARS-CoV-2 re-infection and records with low quality data were excluded. Results: 858 of 3710 of included patients (23%) met PASC criteria. Median follow-up (IQR) for PASC and recovered patients was 180 (98-217) and 180 (90-180) days, respectively. The PASC group had a higher rate of baseline comorbidities and poor performance status (Table). Cancer types, status, and recent anticancer treatment were similar between the groups. The PASC group experienced a higher illness burden, with more hospitalized (83% vs 48%);requiring ICU (29% vs 6%);requiring mechanical ventilation (17% vs 2%);and experiencing co-infections (19% vs 8%). There were more deaths in the PASC vs recovered group (8% vs 3%), with median (IQR) days to death of 158 (120-272) and 180 (130-228), respectively. Of these, 9% were attributed to COVID-19;15% to both COVID-19 and cancer;15% to cancer;and 23% to other causes. Conversely, no deaths in the recovered group were attributed to COVID-19;57% were attributed to cancer;and 24% to other causes (proximal cause of death unknown/missing in 38% and 19%, respectively). Cancer treatment modification was more common in the recovered group (23% vs 18%). Conclusions: Patients with underlying comorbidities, worse ECOG PS, and more severe acute SARS-CoV-2 infection had higher rates of PASC. These patients suffered more severe complications and incurred worse outcomes. There was an appreciable rate of death in both PASC and non-PASC, with cancer the dominant but not only cause in fully recovered patients. Further study is needed to understand what factors drive PASC, and whether longer-term cancer-specific outcomes will be affected.

An update on the overall epidemiology, clinical characteristics, and outcomes from the COVID-19 and Cancer Consortium (CCC19)

Background: Despite mitigation and treatment strategies, COVID-19 continues to negatively impact patients (pts) with cancer. Identifying factors that remain consistently associated with morbidity and mortality is critical for risk identification and care delivery. Methods: Using CCC19 registry data through 12/31/2021 we report clinical outcomes (30-day case fatality rate [CFR], mechanical ventilation use (MV), intensive care unit admission (ICU), and hospitalization) in adult pts with cancer and laboratory confirmed SARS-CoV-2, stratified by patient, cancer, and treatment-related factors. Results: In this cohort of 11,417 pts (with 4% reported vaccination prior to COVID-19), 55% required hospitalization, 15% ICU, 9% MV, and 12% died. Overall outcome rates remained similar for 2020 and 2021 (Table). Hydroxychloroquine was utilized in 11% and other anti-COVID-19 drugs (remdesivir, tocilizumab, convalescent plasma, and/or steroids) in 30%. Higher CFRs were observed in older age, males, Black race, smoking (14%), comorbidities (pulmonary [17%], diabetes mellitus [16%], cardiovascular [19%], renal [21%]), ECOG performance status 2+ (31%), co-infection (25%), especially fungal (35%), and initial presentation with severe COVID-19 (48%). Pts with hematologic malignancy, active/ progressing cancer status, or receiving systemic anti-cancer therapy within 1-3 months prior to COVID-19 also had worse CFRs. CFRs were similar across anti-cancer modalities. Other outcomes (ICU, MV, hospitalization) followed similar distributions by pt characteristics. Conclusions: Unfavorable outcome rates continue to remain high over 2 years, despite fewer case reports in 2021 owing to multiple factors (e.g., pandemic dynamics, respondent fatigue, overwhelmed healthcare systems). Pts with specific socio-demographics, performance status, comorbidities, type and status of cancer, immunosuppressive therapies, and COVID-19 severity at presentation experienced worse COVID-19 severity;and these factors should be further examined through multivariable modeling. Understanding epidemiological features, patient and cancer-related factors, and impact of anti-COVID-19 interventions can help inform risk stratification and interpretation of results from clinical trials.

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).

Code status and outcomes in patients with cancer and COVID- 19: A COVID-19 and cancer consortium (CCC19) registry analysis

Background: In-hospital mortality among patients with cancer (pts) and COVID-19 infection is high. The frequency of, and factors associated with, donot- resuscitate (DNR) or do-not-intubate (DNI) orders at hospital admission (HA), and their correlation with care, has not been well studied. In November 2020, we began collecting this information for pts who were hospitalized at initial presentation in the CCC19 registry (NCT04354701). Methods: We investigated: 1. the frequency of, and factors associated with, DNR/DNI orders at HA;2. change in code status during HA;and 3. the correlation between DNR/DNI orders and palliative care consultation (PC), mortality or length of stay (LOS). We included hospitalized, adult pts with cancer and COVID-19 from 57 participating sites. Reported characteristics include age, ECOG performance status (PS), and cancer status. Comparative statistics include 2-sided Wilcoxon rank sum and Fisher's exact tests. Results: 744 pts had known baseline and/or changed code status (CS);most (79%) maintained their baseline CS (Table). Those with DNR±DNI orders at HA were older (median age 79 vs 69 yrs, p<0.001) and more likely to have: ECOG PS 2+ vs 0-1 (45% vs 22%, OR 3.95, p<0.001), metastatic disease (45% vs 35%, OR 1.72, p=0.005) and progressing cancer (32% vs 16%, OR 2.69, p<0.001), but equally likely to have received systemic anticancer therapy in the prior 3 months (38% vs 45%, p=0.15). N=192 pts with a change in CS from full to DNR±DNI were younger (median age 73), had better PS (37% ECOG PS 2+), and were less likely to have progressing cancer (23%) than those with DNR±DNI orders at baseline. However, their LOS was significantly longer, median 9 vs 6 days, p<0.001. Compared to those with DNR±DNI orders at HA, pts whose CS changed to DNR±DNI were more likely to die, OR 2.94, 95% CI 1.76-4.97, p<0.001. PC was obtained in 106 (14%) pts and associated with transition to DNR±DNI in 47 (44%), affirmation of admission CS in 58 (55%), and reversal in 1 (1%). Median LOS for pts receiving PC was 11 vs 6 days, p<0.001. Conclusions: In our sample, the majority of patients with cancer and COVID-19 were full code at hospital admission. DNR±DNI status, whether at baseline or assigned during the hospital course, was associated with worse prognosis. Longer length of stay for patients changing code status and/or receiving palliative care consultation was observed likely suggesting earlier palliative care consultation is an important, but likely underutilized component in the care of patients with cancer and COVID-19. (Table Presented).