LBA71 Systemic cancer treatment-related outcomes in patients with SARS-CoV-2 infection: A CCC19 registry analysis

Background: SARS-CoV-2 is associated with diverse clinical presentations ranging from asymptomatic infection to lethal complications. Small studies have suggested inferior outcomes in patients (pts) on active cancer treatment. This finding was not independently validated in our prior report on 928 pts, which included treatments administered within 4 weeks of COVID-19 diagnosis. Here, we examine outcomes related to systemic cancer treatment within one year of lab-confirmed SARS-CoV-2 infection in an expanded cohort. Method(s): The COVID-19 and Cancer Consortium (CCC19) registry (NCT04354701) was queried for pts ever receiving systemic treatment. Treatment type, cancer type, stage, and COVID-19 outcomes were examined. Pts were stratified by time from last treatment administration: <2 wk, 2-4 wk, 1-3 mo, or 3-12 mo. Standardized incidence ratios (SIR) of mortality by treatment type and timing were calculated. Result(s): As of 31 July 2020, we analyzed 3920 pts;42% received systemic anti-cancer treatment within 12 mo (Table). 159 distinct medications were administered. The highest rate of COVID-19-associated complications were observed in pts treated within 1-3 months prior to COVID-19;all-cause mortality in this group was 26%. 30-day mortality by most recent treatment type was 20% for chemotherapy, 18% for immunotherapy, 17% for chemoradiotherapy, 29% for chemoimmunotherapy, 20% for targeted therapy, and 11% for endocrine therapy. SIR of mortality was highest for chemoimmunotherapy or chemotherapy <2 wks, and lowest for endocrine treatments. A high SIR was also found for targeted agents within 3-12 mo. Pts untreated in the year prior to COVID-19 diagnosis had a mortality of 14%. [Formula presented] Conclusion(s): 30-day mortality was highest amongst cancer pts treated 1-3 months prior to COVID-19 diagnosis and those treated with chemoimmunotherapy. Except for endocrine therapy, mortality for subgroups was numerically higher than in pts untreated within a year prior to COVID-19 diagnosis. Clinical trial identification: NCT04354701. Legal entity responsible for the study: The COVID-19 and Cancer Consortium (CCC19). Funding(s): National Cancer Institute (P30 CA068485). Disclosure: T.M. Wise-Draper: Research grant/Funding (self), Travel/Accommodation/Expenses: AstraZeneca;Research grant/Funding (self): BMS;Research grant/Funding (self): Tesaro/GSK;Advisory/Consultancy: Shattuck Labs;Leadership role, Travel/Accommodation/Expenses, HNC POA Lead: Caris Life Sciences;Research grant/Funding (self), Travel/Accommodation/Expenses: Merck;Travel/Accommodation/Expenses: Eli Lilly;Travel/Accommodation/Expenses: Bexion. A. Elkrief: Research grant/Funding (self): AstraZeneca. B.I. Rini: Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Merck;Advisory/Consultancy, Research grant/Funding (self): Roche;Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Pfizer;Advisory/Consultancy, Research grant/Funding (self): AVEO;Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: BMS;Advisory/Consultancy: arravive;Advisory/Consultancy: 3D medicines;Advisory/Consultancy: Synthorx;Advisory/Consultancy: Surface Oncology;Shareholder/Stockholder/Stock options: PTC Therapeutics;Research grant/Funding (self): AstraZeneca. D.B. Johnson: Advisory/Consultancy: Array Biopharma;Advisory/Consultancy, Research grant/Funding (self): BMS;Advisory/Consultancy: Janssen;Advisory/Consultancy: Merck;Advisory/Consultancy: Novartis;Research grant/Funding (self): Incyte;Leadership role: ASCO melanoma scientific committee chair;Leadership role: NCCN Melanoma committee. G. Lopes: Honoraria (self), Travel/Accommodation/Expenses: Boehringer Ingelheim;Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer;Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): AstraZeneca;Research grant/Funding (institution): Merck;Research grant/Funding (institution): EMD Serono;Research gr

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.

Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: a report from the COVID-19 and Cancer Consortium.

BACKGROUND: Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies. PATIENTS AND METHODS: Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients). RESULTS: A total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality. CONCLUSIONS: Clinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies. CLINICAL TRIAL IDENTIFIER: NCT04354701.

High mortality among hospital-acquiredCOVID-19 infection in patients with cancer: Anobservational cohort study from Quebec and British Columbia

Background: Studies suggest that patients with cancer are more likely to experience severe outcomes fromCOVID-19. Therefore, cancer centers have undertaken efforts to care for patients with cancer in COVID-free zones.Nevertheless, nosocomial transmission of COVID-19 in patients with cancer likely occurs, but the frequency andrelevance of these events remain unknown. The goal of this study was to determine the incidence and impact ofhospital-acquired COVID-19 in this population and identify prognostic factors for COVID-19 severity in patients withcancer. Methods: Patients with cancer and a laboratory-confirmed or presumed diagnosis of COVID-19 were prospectivelyidentified using provincial registries and hospital databases between March 3rd and May 23rd, 2020, in theprovinces of Quebec and British Columbia. Patients' baseline characteristics including age, sex, comorbidities, cancer type, and type of anticancer treatment were collected. The primary outcome was incidence of hospital-acquired infection defined by diagnosis of SARS-CoV-2 5 days after hospital admission for COVID-unrelated cause. Co-primary outcomes were death or composite outcomes of severe illness from COVID-19 such as hospitalization, supplemental oxygen, intensive-care unit (ICU) admission, and/or mechanical ventilation. Results: A total of 253 patients (N=250 adult and N=3 pediatric) with COVID-19 and cancer were identified, and themajority were residents of Quebec (N=236). Ninety patients (35.6%) received active anticancer treatment in the last3 months prior to COVID-19 diagnosis. During a median follow-up of 23 days, 209 (82.6%) required hospitalization,38 (15%) required admission to ICU, and 71 (28%) died. Forty-seven (19%) had a diagnosis of hospital-acquiredCOVID-19. Median overall survival was shorter in those with hospital-acquired infection, compared to acontemporary community-acquired population (27 days vs. 71 days, HR 2.2, 95% CI 1.2-4.0, p=0.002). Multivariateanalysis demonstrated that hospital-acquired COVID-19, age, ECOG status, and advanced stage of cancer wereindependently associated with death. Conclusion: Our study demonstrates a high rate of nosocomial transmission of COVID-19, associated withincreased mortality in both univariate and multivariate analysis in the cancer population, reinforcing the importanceof treating patients with cancer in COVID-free zones. We also validated that age, poor ECOG, and advanced cancer were negative prognostic factors for COVID-19 in patients with cancer.

Clinical characteristics and outcomes ofcoronavirus 2019 disease (COVID-19) in cancer patientstreated with immune checkpoint inhibitors (ICI)

Background: ICI are widely used in the treatment of various cancer types. It has been hypothesized that ICI couldconfer an increased risk of severe acute lung injury or other complications associated with severe acute respiratorysyndrome coronavirus 2 (SARS-CoV-2). Methods: We analyzed data from 113 patients with laboratory-confirmed COVID-19 while on treatment with ICI without chemotherapy in 19 hospitals in North America, Europe, and Australia. Data collected included details onsymptoms, comorbidities, medications, treatments and investigations for COVID-19, and outcomes (hospitaladmission, ICU admission, and mortality). Results: The median age was 63 years (range 27-86);40 (35%) patients were female. Most common malignancies were melanoma (n=64, 57%), non-small cell lung cancer (n=19, 17%), and renal cell carcinoma (n=11, 10%);30(27%) patients were treated for early (neoadjuvant/adjuvant) and 83 (73%) for advanced cancer. Most patientsreceived anti-PD-1 (n=85, 75%), combination anti-PD-1 and anti-CTLA-4 (n=15, 13%), or anti-PD-L1 (n=8, 7%) ICI.Comorbidities included cardiovascular disease (n=31, 27%), diabetes (n=17, 15%), and pulmonary disease (n=14, 12%). Symptoms were present in 68 (60%) patients;46 (68%) had fever, 40 (59%) cough, and 23 (34%) dyspnea.Overall, ICI was interrupted in 58 (51%) patients. At data cutoff, 33 (29%) patients were admitted to hospital, 6 (5%)to ICU, and 9 (8%) patients died. COVID-19 was the primary cause of death in 7 patients, 3 of whom were admittedto ICU. Cancer types in patients who died were melanoma (2), non-small cell lung cancer (2), renal cell carcinoma(2), and others (3);all (9) patients had advanced cancer. Administered treatments were oxygen therapy (8), mechanical ventilation (2), vasopression (2), antibiotics (7), antiviral drugs (4), glucocorticoids (2), and anti-IL-6 (2).Of all hospitalized patients, 20 (61%) had been discharged and 4 (12%) were still in hospital at data cutoff. Conclusion: The mortality rate of COVID-19 in patients on ICI is higher than rates reported for the generalpopulation without comorbidities but may not be higher than rates reported for the cancer population. Despite thesepreliminary findings, COVID-19 patients on ICI may not have symptoms and a proportion may continue ICI.Correlative analyses are ongoing and will be presented.

Changes in lung cancer treatment as aresult of the COVID19 pandemic: A prospectiveobservational study

Background: Patients with lung cancer are at high risk from COVID19. Efforts are ongoing to limit exposure ofpatients with lung cancer to the health care system. As a result, the COVID19 pandemic has drastically changedcancer care, but the extent and type of these changes are unknown. The goal of this study was to evaluate thechanges in lung cancer treatment during the peak of the COVID19 pandemic. Methods: We prospectively assessed the cancer management plan of all patients seen in the thoracic oncologyclinic at our center between March 2 and April 30, 2020. Inclusion criteria for this study were a diagnosis of eithernon-small cell lung cancer or small-cell lung cancer. Those who had a diagnosis of COVID19 were excluded fromthe study. Primary endpoints were to describe the extent of changes in the cancer treatment plan and qualify thetypes of changes observed. Results: A total of N=289 patients were evaluated between March 2 and April 30, 2020. N=14 patients wereexcluded due to presence of other tumor histology, and 2 patients were COVID19-positive. Among the 275 patientsincluded, median age was 68 and 47% were male. Among the 238 patients (86.5%) with non-small cell lung cancer,172 (62.5%) had advanced disease. Among the 37 patients (13.5%) with small-cell lung cancer, 11 (4%) hadextensive disease. 211 were receiving active treatment (76.5%), with 35.1% on chemotherapy, 21.8% on oralagents, 31.8% on immune checkpoint inhibitors, and 11.4% on combination therapy. 121 (57%) of patientsexperienced at least one change in their lung cancer treatment plan as a direct result of the COVID19 pandemic, with 19 (9.0%) patients experiencing more than one change. The majority of changes encompassed delay orcessation of palliative treatment, N=48 (39.7%), N=18 (14.9%), respectively. Mean time to resumption of palliativetreatment was 36 days, and 3% of patients stopped palliative treatment permanently as a direct result of thepandemic. Changes in dosing and schedule occurred in N=32 (26.4%), which included changing pembrolizumab toq 6 weeks or durvalumab to q 4 weeks. A minority of patients experienced delays in adjuvant chemotherapyadministration (N=3 (2.5%)) with a mean delay of 42 days. Lastly, 6.6% of patients experienced deferrals orcancellations of surveillance scans or visits due to COVID19. Other changes included the decision not to pursuepalliative chemotherapy. Conclusion: Our study demonstrated that a significant proportion (57%) of patients experienced changes in theirlung cancer management plan as a direct result of the COVID19 pandemic. Given the preliminary findings thatactive cancer treatment is not associated with increased complications from COVID19, lung cancer treatments andsurveillance visits should continue to proceed with caution, and oncology care providers should continue to carefullyproceed with evidence-based care in lung cancer.