Monoclonal Antibody Therapy for COVID-19: A Public Health Perspective From Arkansas

COVID-19 monoclonal antibodies revolutionized the treatment for eligible patients who have tested positive for SARS CoV-2 infection in an ambulatory setting. In this short report, we describe our experience assisting in the distribution of monoclonal antibodies in Arkansas during the summer surge of the delta variant.

Real-world clinical outcomes of treatment with casirivimab-imdevimab among patients with mild-to-moderate coronavirus disease 2019 during the Delta variant pandemic

Background: Mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may reduce the efficacy of neutralizing monoclonal antibody therapy against coronavirus disease 2019 (COVID-19). We here evaluated the efficacy of casirivimab-imdevimab in patients with mild-to-moderate COVID-19 during the Delta variant surge in Fukushima Prefecture, Japan. Methods: We enrolled 949 patients with mild-to-moderate COVID-19 who were admitted to hospital between July 24, 2021 and September 30, 2021. Clinical deterioration after admission was compared between casirivimab-imdevimab users (n = 314) and non-users (n = 635). Results: The casirivimab-imdevimab users were older (P < 0.0001), had higher body temperature (≥ 38 degree) (P < 0.0001) and greater rates of history of cigarette smoking (P = 0.0068), hypertension (P = 0.0004), obesity (P < 0.0001), and dyslipidemia (P < 0.0001) than the non-users. Multivariate logistic regression analysis demonstrated that receiving casirivimab-imdevimab was an independent factor for preventing deterioration (odds ratio 0.448; 95% confidence interval 0.263 to 0.763; P = 0.0023). Furthermore, in 222 patients who were selected from each group after matching on the propensity score, deterioration was significantly lower among those receiving casirivimab-imdevimab compared to those not receiving casirivimab-imdevimab (7.66% vs 14.0%; p = 0.021). Conclusion: This real-world study demonstrates that casirivimab-imdevimab contributes to the prevention of deterioration in COVID-19 patients after hospitalization during a Delta variant surge.

Incidence and Characteristics of CD20 Monoclonal Antibody-Induced Interstitial Pneumonitis

Background: CD20 monoclonal antibody therapy is the backbone of treatment for B-cell non-Hodgkin lymphoma. Several studies have described an association between the use of rituximab and non-infectious interstitial pneumonitis, with estimates ranging from 3.9% to 8.4%. 1-3 However, several novel CD20 monoclonal antibodies have been introduced in the past decade, with obinutuzumab gaining FDA approval in 2013, ofatumumab first approved in 2014, and rituximab/hyaluronidase human approved as a subcutaneous route of rituximab in 2017. While the use of these agents has rapidly increased in clinical practice, the incidence of pneumonitis with these agents is not well known. Thus, we have performed a retrospective review of patients with B cell lymphoma treated with CD20 monoclonal antibody therapy to determine the incidence and characteristics of pneumonitis with these novel agents. Methods: We evaluated all patients at the University of North Carolina at Chapel Hill with B-cell lymphoma who were treated with CD20 monoclonal antibody therapy from 2014 to 2020. We performed individual chart review to verify the presence of interstitial pneumonitis, as defined by presence of respiratory symptoms (cough, dyspnea, fever, chest pain) in addition to imaging findings (pulmonary opacity on chest X-ray and/or ground glass opacities on chest computed tomography (CT)) without alternative cause (CHF with pulmonary edema, COPD flare, infectious cause including bacterial, fungal or viral pneumonia/bronchitis). We extracted demographic data, comorbid conditions, tobacco use history, and timing of pneumonitis related to CD20 monoclonal antibody exposure. We determined rates of pneumonitis based on agent and chemotherapy backbone. Results: We identified 18 cases of chart-confirmed interstitial pneumonitis over a six-year period, out of 2,207 patients treated with CD20-monoclonal antibody therapy. Seven (39%) were current or former smokers, with a median of 30 pack-years smoked. Five (29%) had a history of hypersensitivity reaction to rituximab infusion. Pneumonitis developed after a median of 4 cycles, and 16 days from the most recent CD20 monoclonal antibody infusion. Ten (56%) had diffuse large B-cell lymphoma, 4 (22%) had mantle cell lymphoma, and 1 (6%) each had follicular lymphoma, chronic lymphocytic leukemia, hairy cell leukemia, and Waldenstrom's macroglobulinemia. Eight cases (44%) occurred among patients being treated with R-CHOP, 2 (11%) were treated with BR, 2 (11%) were receiving single agent rituximab, although several other regimens were represented. Most cases occurred in patients being treated with infusional rituximab, but the rate remained quite low (14/1654, 0.8%). Four occurred in patients receiving subcutaneous rituximab hycela out of 167 treated patients (2.4%), less than prior estimates of pneumonitis with monoclonal antibody therapy. Most cases of pneumonitis were treated with steroids (n=15, 83%), although none required infliximab or anti-TNF agents, and no cases of pneumonitis were fatal. Most notably, we did not identify any cases of pneumonitis among patients treated with ofatumumab (n=51) or obinutuzumab (n=58). Conclusion: This retrospective review reinforced the safety of novel anti-CD20 agents, with low rates of interstitial pneumonitis among patients treated with infusional or subcutaneous rituximab. Cases that did occur were effectively treated with steroids, and there were no fatalities associated with pneumonitis. Ofatumumab and obinutuzumab were not associated with any cases of interstitial pneumonitis. Bibliography 1. Katsuya H, Suzumiya J, Sasaki H, et al. Addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy has a high risk of developing interstitial pneumonia in patients with non-Hodgkin lymphoma. Leuk Lymphoma. 2009;50(11):1818-1823. doi:10.3109/10428190903258780 2. Salmasi G, Li M, Sivabalasundaram V, et al. Incidence of pneumonitis in patients with non-Hodgkin lymphoma receiving chemoimmunotherapy with rituximab. Leuk Lymphoma. 2015;56(6):1659-1664. doi:10.3109/10428194.2014.963075 3. Liu X, Hong X-N, Gu Y-J, Wang B-Y, Luo Z-G, Cao J. Interstitial pneumonitis during rituximab-containing chemotherapy for non-Hodgkin lymphoma. Leuk Lymphoma. 2008;49(9):1778-1783. doi:10.1080/10428190802270886 Figure 1 Figure 1. Disclosures Grover: Novartis: Consultancy; Genentech: Research Funding; ADC: Other: Advisory Board; Kite: Other: Advisory Board; Tessa: Consultancy. Dittus: BeiGene: Other: Advisory Board; Seattle Genetics: Research Funding; AstraZeneca: Research Funding; Genentech: Research Funding.

513. Use of Antimicrobial Stewardship Program in Operationalizing Monoclonal Antibody Therapy in SARS-CoV-2 Infection

Background Antimicrobial stewardship programs (ASP) have been essential during the coronavirus disease 2019 (COVID-19) pandemic response. Use of monoclonal antibodies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has proven difficult to operationalize, despite being available through emergency use authorization (EUA). Utilizing existing ASP and multidisciplinary approach to lead the effort, we aim to describe our experience in operationalizing monoclonal antibody therapy. Methods Retrospective study of SARS-CoV-2 infected adults receiving monoclonal antibody therapy under EUA (December 2020-April 2021). An algorithm developed by the ASP provided education and an interactive online tool allowing referring physicians and patients to assess eligibility prior to hospital arrival. Patients were screened and approved by existing ASP which included; Infectious Disease (ID) physicians, pharmacist, and ID Nurse. A multidisciplinary approach with ER staff and development of pharmacy workflow with order set were utilized as eligible patients received infusion in dedicated ER location. Data such as demographics, co-morbid condition, infusion related complications, hospitalization, and death were reviewed and collected regularly by the ASP team with frequent monitoring and regulatory reporting. Primary patient outcome was preventing hospitalization. Results 107 patients received monoclonal antibody therapy. 47% patients were male, 50% White, and 79% non-Hispanic. 87% received monotherapy (bamlanivimab) and 13% received dual therapy (bamlanivimab/etesevimab). 17 patients required hospitalization post infusion. 1 death occurred. COVID-19 related hospitalization within 30-days was avoided in 84% of treated patients. No adverse event directly related to infusion were seen. Conclusion Use of monoclonal antibody therapy under EUA for patients for SARS-CoV-2 infection led to decrease in hospitalization in this cohort. An existing ASP using an algorithmic approval process, frequent monitoring, and multidisciplinary approach successfully operationalized the use of monoclonal antibody therapy. ASP’s provide benefit and versatility beyond monitoring of antimicrobials alone and should continue to receive support by hospital leadership. Disclosures All Authors: No reported disclosures

535. Comparison of Outcomes in Patients Positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection After Monoclonal Antibody Therapy (MAT) with Bamlamivimab or Casirivimab-Imdevimab

Background Limited options currently exist for treatment of patients diagnosed with symptomatic coronavirus 2019 (COVID-19). Monoclonal antibody therapy (MAT) has been investigated as a therapeutic option for symptomatic COVID-19 patients in the outpatient setting at high-risk for progression to severe disease based on emergency use authorization (EUA) criteria. No published studies have compared outcomes for patients treated with different MAT for COVID-19. Methods This was a single-center, retrospective cohort study at The Ohio State University Wexner Medical Center to compare COVID-19-related emergency room (ER) visits, admissions, and mortality at 30 days after MAT infusion for adult patients with symptomatic SARS-CoV-2 between November 16, 2020 and February 2, 2021 who received bamlanivimab versus those who received casirivimab-imdevimab. Statistical analysis used logistic regression analysis to determine the odds ratio (OR) to evaluate the relationship between patient characteristics, MAT, and outcomes. Results The cohort included 943 patients with SARS-CoV-2 who received MAT, including 658 patients who received bamlanivimab and 285 who received casirivimab-imdevimab. Outcome results between patients who received bamlanivimab and casirivimab-imdevimab showed no statistically significant difference seen in the number of COVID-19 related ER visits (3.2% vs 3.5%, p = 0.80), hospital admissions (4.6% vs 2.8%, p = 0.21), or mortality (0.5% vs 0.7%, p = 0.63). Multivariate analysis showed no statistically significant difference in outcomes between the groups when accounting for potential confounders. As reflected in the Table, chronic lymphocytic leukemia (CLL), gender, and asthma were associated with increased COVID-19 related ER visit within 30 days of infusion and age, chronic obstructive pulmonary disease, CLL, and lupus were associated with increased risk for COVID-19 related admission within 30 days of infusion. Age and obesity with body mass index greater than 35 mg/kg2 were associated with increased risk for COVID-19 related mortality at 30 days. Conclusion COVID-19 related outcomes were similar when comparing patients with COVID-19 treated with bamlanivimab versus those treated with casirivimab-imdevimab. Disclosures Mohammad Mahdee Sobhanie, M.D., Regeneron (Scientific Research Study Investigator)Regeneron (Scientific Research Study Investigator, Was a sub-investigator for Regeneron 2066 and 2069) Carlos Malvestutto, M.D., Lilly (Scientific Research Study Investigator)Regeneron Inc. (Scientific Research Study Investigator)ViiV Healthcare (Advisor or Review Panel member)