COVID-19 in a Comprehensive Cancer Center: 2020-2022

Background. Patients with COVID-19 and underlying malignancies, particularly those receiving immunosuppressive therapy, are at higher risk of severe COVID-19 disease. Our retrospective cohort study examines the outcomes of COVID-19 infection in patients with different underlying malignancies admitted to a 710- beds comprehensive cancer center during the first 2 years of the pandemic. Methods. All patients with cancer admitted to MD Anderson Cancer Center with a positive PCR test for SARS-CoV-2 were included in a clinical case registry from 3/22/20 (first hospitalized COVID-19 patient) to 3/31/22. This clinical registry was approved at the beginning of the COVID-19 pandemic by the Quality Improvement Assessment Board at MDACC. Clinical information including type of malignancy, date of admission, length of stay, need for invasive mechanical ventilation (IMV), and in-hospital mortality was obtained from their electronic medical records. Statistical analysis was performed using a two-proportion z-test where p< 0.05 was considered significant. Results. A total of 1748 patients with cancer and COVID-19 infection were admitted over a 2-year period (3.2% of total hospital admissions during the same period), 49% had hematological malignancies (HM) (see table). Patients with HM had significantly higher readmission rates (17.3% vs 9.1%, p< 0.0001), IMV rates (7.8% vs 4.4%, p=0.0029), and inpatient mortality rates (13.6% vs 7.1%, p< 0.0001). compared to patients with solid tumors (ST). Total mortality rate was 8.8% (154 patients), even higher in patients with different types of HM, such as lymphoma 18.1%, AML 14.2%, MM 8.4%, CML 7.1% while the mortality for ST was 7.1%. COVID-19 Hospitalized Patients at UT-MDACC (3/22/20-3/31/22) UT-MDACC: The University of Texas MD Anderson Cancer Center *p-value <0.01 for z-test of 2 proportions (one-tailed) Conclusion. HM patients hospitalized with COVID-19 infection had more severe disease and worse outcomes based on readmissions, IMV, and mortality rates. Preventive measures, prompt diagnosis and early treatments should be considered on this patient population.

INTERSTITIAL LUNG DISEASE AFTER COVID-19 IN PATIENTS WITH CANCER AND WITHOUT: A PROSPECTIVE COHORT STUDY

SESSION TITLE: Long COVID: It Can Take Your Breath Away SESSION TYPE: Original Investigations PRESENTED ON: 10/16/2022 10:30 am - 11:30 am PURPOSE: Survivors of COVID-19 hospitaliaztion may be at high risk for interstitial lung disease (ILD). The incidence and natural history of post-COVID ILD may vary in cancer and non-cancer patients, particularly if survival is lower in cancer patients. We sought to determine the incidence of ILD at 3 and 6 months after hospital discharge in cancer and non-cancer patients METHODS: We analyzed a prospective cohort of patients discharged after COVID-19 hospitalization between March 2020 and March 2021. Cancer patients were referred to post-COVID clinics 3 months after discharge, while non-cancer patients self-referred to post-COVID clinics at a tertiary referral center. We classified patients into 4 groups: Group 1, asymptomatic without ILD;Group 2, symptomatic without ILD;Group 3, ILD with spontaneous improvement by 6 months;Group 4, persistent ILD at 6 months. Group 1 patients were not seen after initial visits, while all others returned at 6 and 12 months after discharge. We hypothesized that initial COVID-19 severity, measured by the Radiologic Severity Index (RSI) on admission CT, would be associated with irreversible ILD. RSI measures radiologic severity by measuring percentage of involvement (normal - 0, <25% involvement-1, 25-50% involvement-2, 50-75% involvement-3, >75% involvement–4) and multiplying by a score based on the predominant pattern of infiltrate (normal-1, ground glass-2, consolidation-3) in six zones (left, right;upper, middle, lower) to yield a score between 0-72. We used logistic regression to measure whether admission CT RSI was associated with ILD at 3 months. RESULTS: 609 cancer patients were hospitalized with COVID-19 during the study period, of whom 85 (14%) died in-hospital, and 31 (5%) were sent home to hospice. A further 63 (10%) patients died before post-COVID evaluation. Similar data were not available for non-cancer patients due to self-referral. 98 cancer patients and 75 non-cancer patients were seen in post-COVID clinics. Among cancer patients, 20 were Group 1 (20%);8, Group 2 (8%);42, Group 3 (43%);24, Group 4 (25%);5 (5%) lacked post-COVID imaging. ILD was seen in 68% of patients at 3 months, but only in 25% at 6 months. 6% of all hospitalized cancer patients developed ILD. Among non-cancer patients: Group 1, 2 patients (3%);Group 2, 3 patients (4%);Group 3, 26 patients (35%);Group 4, 14 patients (19%);30 (40%) had no post-COVID imaging. Higher RSI at COVID admission associated with ILD at 3 months in non-cancer patients (OR 1.03, 95% CI 1.00-1.07, p=0.054) but not cancer patients (OR 1.3, 95% CI 0.4-4.5). CONCLUSIONS: Initial COVID-19 severity is associated with ILD 3 months after discharge in non-cancer patients but not cancer patients. CLINICAL IMPLICATIONS: ILD is common in survivors of COVID-19 hospitalization, particularly in non-cancer patients hospitalized for severe infection. These data may guide patient selection for referral to post-COVID clinics. DISCLOSURES: No relevant relationships by Roberto Adachi No relevant relationships by Diwakar Balachandran No relevant relationships by Lara Bashoura No relevant relationships by Christopher Bertini No relevant relationships by Kodwo Dickson Owner/Founder relationship with Pulmotect, Inc Please note: 2010-present by Scott Evans, value=Royalty No relevant relationships by Saadia Faiz no disclosure on file for Bruno Granwehr;no disclosure submitted for Shannon Holloway;No relevant relationships by Maryam Kaous no disclosure on file for Fareed Khawaja;No relevant relationships by Lyndon Lee No relevant relationships by Joanna Manzano No relevant relationships by Isabel Mira-Avendano No relevant relationships by Alyssa Mohammed No relevant relationships by Mayoora Muthu No relevant relationships by Sungryong Noh Research relationship with United Therapeutics;PhaseBio Please note: $5001 - $20000 by Bela Patel, value=Grant/Research No relevant relationships by Vickie Shannon onsultant relationship with Psioxus Therapeutics Please note: 3/1/20-7/1/20 by Ajay Sheshadri, value=Consulting fee Consultant relationship with Enanta Pharmaceuticals Please note: 01/01/21-ongoing by Ajay Sheshadri, value=Consulting fee No relevant relationships by Hui Song

International Multicenter Study Comparing Cancer to Non-Cancer Patients with COVID-19: Impact of Risk Factors and Treatment Modalities on Outcome

Background. Given the limited collaborative international studies that evaluated COVID-19 in patients with cancer in comparison to patients without cancer, we aimed to determine the independent risk factors associated with increased 30-day mortality and the impact of novel treatment modalities in a large group of cancer and non-cancer patients with COVID-19 from multiple countries. Methods. We retrospectively collected de-identified data on cancer and non-cancer patients diagnosed with COVID-19 between January and November 2020, at 16 centers in Asia, Australia, Europe, North America, and South America. A logistic regression model was used to identify independent predictors of all-cause mortality within 30 days after COVID-19 diagnosis. Results. Of the total 4015 COVID-19 confirmed patients entered, we analyzed 3966 patients, 1115 cancer and 2851 non-cancer patients. Cancer patients were older than non-cancer patients (median age, 61 vs 50 years;p< 0.0001);more likely to be pancytopenic , had pulmonary disorders, hypertension, diabetes mellitus. In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin and procalcitonin), but were less likely to present with clinical symptoms. By multivariable logistic regression analysis, cancer was an independent risk factor for 30-day mortality (OR 1.46;95% CI 1.03 to 2.07;p=0.035). Older age (≥65 years) was the strongest predictor of 30-day mortality in all patients (OR 4.55;95% CI 3.34 to 6.20;p< 0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30-day mortality (OR 0.58;CI 0.39-0.88;p=0.009). Among patients on lowflow oxygen at admission, patients who received remdesivir had a lower 30-day mortality rate than those who were on high flow oxygen (5.9% vs 17.6%;p=0.03). Patients transfused with convalescent plasma within 1 day of diagnosis had a lower 30-day mortality rate than those transfused later (1% vs 7%, p=0.04). Conclusion. Cancer is an independent risk factor for increased 30-day all-cause mortality from COVID-19. Remdesivir, particularly in patients receiving low-flow oxygen, can reduce 30-day all-cause mortality, as well as convalescent plasma given early after COVID-19 diagnosis.

Long COVID in Cancer Patients: Preponderance of Symptoms in Majority of Patients over Long Time Period

Background. An increasing number of observational studies have reported the persistence of symptoms following recovery from acute COVID-19 disease. The long-term consequences of COVID-19 are not fully understood and there is no clear consensus on the definition of post-acute sequelae of SARS-CoV-2 infection (PASC). The reported prevalence of PASC widely varies from 10% up to 87%. The purpose of this study is to assess PASC in cancer patients following acute COVID-19 recovery. Methods. We assessed cancer patients at MD Anderson Cancer Center who were diagnosed with COVID-19 disease between March 1, 2020 and Sept 1, 2020. Using patient questionnaires and medical chart reviews we followed these patients from March 2020 till May 2021. Patient questionnaires were sent out remotely daily for 14 days after COVID-19 diagnosis then weekly for 3 months, and then monthly thereafter. Chart reviews were conducted for each patient hospital re-admission and emergency department visit. These admissions were classified as either COVID-19 related or non-related. The persistence or emergence of new COVID19-related symptoms were captured at each COVID-19 related admission. Results. We included 312 cancer patients with a median age of 57 years (18-86). The majority of patients had solid tumors (75%). Of the 312 patients, 188 (60%) reported long COVID-19 symptoms with a median duration of 7 months and up to 14 months after COVID-19 diagnosis. The most common symptoms reported included fatigue (82%), sleep disturbances (78%), myalgias (67%) and gastrointestinal symptoms (61%), followed by headache, altered smell or taste, dyspnea (47%) and cough (46%). A higher number of females reported a persistence of symptoms compared to males (63% vs 37%;p=0.036). Cancer type, neutropenia, lymphocytopenia, and hospital admission during acute COVID-19 disease were comparable in both groups and did not seem to contribute to a higher number of long-COVID-19 patients in our study group. Conclusion. Long-COVID occurs in 60% of cancer patients and may persist up to 14 months after acute illness. The most common symptoms are fatigue, sleep disturbance, myalgia and gastro-intestinal symptoms.

Implementation of a novel patientreported outcomes measure for patients with cancer and COVID-19 infection

Background: The long-term symptoms from COVID-19 (C19) infection in pts with cancer is not fully known. To monitor the evolution of this symptom burden over time, we designed and implemented a C19-specific patient-reported outcome (PRO) measure that integrated with a known measure of cancer symptom burden. Methods: Within the institutional initiative on C19 and cancer named Data-Driven Determinants for C19 Oncology Discovery Effort (D3CODE), pts with cancer & PCR-pos C19 are invited to participate in this longitudinal study. Pts complete the EQ-5D-5L, the 13 symptom severity & 6 interference items of the core MD Anderson Symptom Inventory (MDASI)+14 COVID-specific items, all scored on a 0-10 scale, 0 = none, 10 = worst imaginable. Pts complete the survey daily x 14 days from positive test date, then weekly x 3months, then monthly x 2yrs. Demographic and disease information was collected. Psychometric procedures determined validity and reliability of the MDASI-COVID. Results: Between 5/15/20-02/14/21, 2154 pts w PCR-confirmed C19 were invited to participate in the longitudinal study. 1282 (60%) pts provided consent and began the longitudinal completion of PRO surveys. Pts were 54.5% Female and 45.5% Male, median age 59 years (range 15-92). 1021 (80%) are White/Caucasian, 206 (16%) Hispanic, 113 (9%) African American, and 39 (3%) Asian. The validation analysis of MDASI-COVID instrument included the 1 600 pts where the mean overall health rating on EQ-5D-5L was 78.3 (SD 19.6), best being 100. Highest mean (M) severity symptoms on the MDASI-COVID were fatigue (M 3.45, SD 2.17), drowsiness (M 2.50, SD 2.89), sleep disturbance (M 2.44, SD 2.99), malaise (M 2.37, SD 3.05), and distress (M 2.27, SD 2.90). Most severe (≥ 7) symptoms) reported were fatigue (21.3% of pts), change in taste (14.8%), change in smell (14.4%), malaise (14.3%), sleep disturbance (14.3%), and drowsiness (14%). showed internal consistency (Cronbach α) of the 27 symptom items was 0.957, of the 6 interference items was 0.937. Mean severity of the 27 symptom items was significantly correlated with overall EQ-5D-5L health rating (correlation =-0.45, P < 0.0005), demonstrating concurrent validity. Mean symptom severity and interference showed known-group validity between pts who required hospitalization (symptom M 2.32, SD 2.09;interference M 3.29, SD 3.02) and those who did not (symptom M 1.69, SD 1.85;interference M 2.20, SD 2.64) (symptom P 0.007;interference P 0.004). Conclusions: We successfully deployed a PRObased long-term symptom monitoring platform for pts with C19 and cancer. The validation analysis of this novel C19 specific PRO, the MDASI-COVID, AIDS in the quantification of the global symptom burden in pts with both cancer and COVID-19 infection. Deployment of this measure in the ongoing longitudinal observational cohort allows for in-depth understanding of the long-term symptoms related to C19 and cancer.

Real-world patient-reported and clinical outcomes of BNT162b2 mRNA COVID-19 vaccine in patients with cancer

Background: Most COVID-19 (C19) vaccine trials excluded patients with active cancer. Here, we report our real-world patient-reported and clinical outcomes of BNT162b2 mRNA C19 vaccine in patients with cancer. Methods: Our institutional Data-Driven Determinants for COVID-19 Oncology Discovery Effort (D3CODE) follows a longitudinal observational cohort of pts w cancer getting C19 vaccine. Pts complete a validated PRO tool, MD Anderson Symptom Inventory (MDASI, 13 core, 6 interference plus 17 items of symptoms from prior vaccine trials) pre-dose 1, then daily x 6d, then weekly, then on day of dose 2, then daily x 6d, then weekly x 3w. Demographics, cancer variables, prior immune checkpoint inhibitors (ICI), C19 status pre- & post-vaccine are aggregated via Syntropy platform: Palantir Foundry. Primary outcome is incidence of PRO symptoms bw dose 1 & 2 across AYA 15-39y, mid-age 40-64y & senior 65y+ cohorts. Secondary outcomes include PRO symptom incidence post-dose 2, post-vaccine change in cancer symptoms, post-vaccine symptom severity based on prior ICI, and confirmed C19 > 7 days post-dose 2. First planned 8-wk interim analysis is reported here. Results: 6388 pts w cancer (4973 w mets) received a BNT162b2 vaccine dose (4811 both doses, 1577 received one & await dose 2). Overall, median age 64y (range 16-95y);382 AYAs, 2927 mid-age, 3079 seniors (65-70y n = 1158, 70-79y n = 1521, 80-89y n = 378, 90y+ n = 22). 4099 (64%) are White, 823 (13%) AA, 791 (12%) Hispanic, 441 (7%) Asians. Primary cancers: breast (1397), GU (821), heme (775), thoracic/HN (745), and CRC (385). Prior to dose 1, 1862 had no prior systemic tx while 4526 pts did including 3243 who had only non-IO tx (chemo, targeted tx), 1,283 had immunotherapy including 857 who had ICIs prior to dose 1. Patient-reported symptoms after C19 Vaccine: Of 6388 pts, 4714 (74% response rate, median age 67y, range 16-95y) completed 16485 PRO surveys. After 2 doses, seniors reported lower mean scores vs mid-age or AYAs on 22 of 36 symptoms including injection site pain, palpitations, itch, rash, malaise, fevers/chills, arthralgia, myalgia, headache, pain, fatigue, nausea, disturbed sleep, distress (p < 0.05). Pts w prior ICIs had higher severity of itch, rash (p < 0.05) from baseline after both dose 1 & 2 vs pts without systemic tx. Post dose 1, pts with prior ICI had higher increase in fatigue, malaise, itch, rash, myalgia, anorexia from their baseline vs pts without systemic tx (p < 0.05). C19 Outcomes: Of 6388 pts, 616 had a C19 test at any time post-dose 1: 23 (0.36%) tested positive of whom 20 (0.3%) were between dose 1 & 2;two (0.031%) were within 7 days post-dose 2, and one patient (0.016%) tested positive 16 days after dose 2, requiring admission. Conclusions: This real-world observational cohort demonstrates post-vaccine symptom burden and outcomes in patients with cancer. Second interim analysis is planned at 16 weeks.

Development and validation of a novel patient-reported outcomes (PRO) measure for symptom burden in patients with cancer and COVID-19 infection

Background: The symptom burden experienced by patients with cancer who contract the COVID-19 (C19) infection remains to be fully understood. To accurately assess this symptom burden, we developed a valid, reliable patient-reported outcome (PRO) measure of C19 symptoms combined with a known measure of cancer symptom burden. Methods: Within the institutional initiative on COVID-19 and cancer named Data- Driven Determinants for COVID-19 Oncology Discovery Effort (D3CODE), patients with cancer and PCR-positive C19 tests were invited to participate in this longitudinal study after providing consent. Pts completed the EQ-5D-5L and the 13 symptom severity and 6 interference items of the core MD Anderson Symptom Inventory (MDASI) plus 14 COVID-specific symptom items generated from literature and expert review. Items were measured on a 0-10 scale, 0 = none to 10 = worst imaginable symptom or interference. Demographic and disease information was collected. Psychometric procedures determined validity and reliability of the MDASI-COVID. Results: 600 pts enrolled, mean age 56.5y (range 20 to 91y). 59% female, 80% white. 78% solid tumors, 19% heme cancers. 12.5% required hospitalization for C19. Median number of days between positive C19 test and PRO completion was 17 days. Mean overall health rating on EQ-5D-5L was 78.3 (SD 19.6), best being 100. Highest mean (M) severity symptoms on the MDASI-COVID were fatigue (M 3.45, SD 2.17), drowsiness (M 2.50, SD 2.89), sleep disturbance (M 2.44, SD 2.99), malaise (M 2.37, SD 3.05), and distress (M 2.27, SD 2.90). Most severe (≥ 7) symptoms) reported were fatigue (21.3% of pts), change in taste (14.8%), change in smell (14.4%), malaise (14.3%), sleep disturbance (14.3%), and drowsiness (14%). Internal consistency (Cronbach α) of the 27 symptom items was 0.957, of the 6 interference items was 0.937. Mean severity of the 27 symptom items was significantly correlated with overall EQ-5D-5L health rating (correlation = -0.45, P < 0.0005), demonstrating concurrent validity. Mean symptom severity and interference showed known-group validity between patients who required C19 hospitalization (symptom M 2.32, SD 2.09;interference M 3.29, SD 3.02) and those who did not (symptom M 1.69, SD 1.85;interference M 2.20, SD 2.64) (symptom P 0.007;interference P 0.004). Conclusions: We have validated a novel PRO, the MDASI-COVID, to quantify the combined symptom burden in patients with cancer and COVID-19. This measure allows longitudinal evaluation of COVID-19 on cancer symptom burden and provide clinicians with an accurate tool for ongoing symptom assessment and management. Longitudinal analysis on long-term symptoms related to COVID-19 and cancer are ongoing.