Casirivimab-imdevimab for Treatment of COVID-19 in Solid Organ Transplant Recipients: An Early Experience

Abstract

Casirivimab-imdevimab is a formulation of 2 recombinant human immunoglobulin G1 monoclonal antibodies (MABs) that targets the receptor-binding domain of the spike protein of severe acute respiratory syndrome coronavirus-2, blocking the viral attachment and entry into human cells. Casirivimab-imdevimab and bamlanivimab are the 2 coronavirus disease 2019 (COVID-19) MABs to receive Emergency Use Authorization by the US Food and Drug Administration for the treatment of patients with mild-to-moderate COVID-19 who are at high risk for progression to severe disease.1 Solid organ transplant (SOT) recipients may be at a higher risk of hospitalization, intensive care unit stays, and death when compared with the general population.2 Among predefined high-risk patients with COVID-19, 3% of those treated with casirivimab-imdevimab compared with 9% who received placebo required hospitalization or emergency room visit.1,3 Data regarding safety and efficacy of MABs in SOT recipients are limited. During our experience from March to August 2020, in 59 adult SOT patients diagnosed with COVID-19 at Westchester Medical Center, New York, 63% required hospitalization, 19% an intensive care unit stay, 14% mechanical ventilation, and 12% died. Based on its initial favorable response in the clinical trials and subsequent Food and Drug Administration authorization in November 2020, we have used a COVID-19 MAB for all our eligible adult SOT patients. During the "second surge," between November 2020 and late January 2021, 54 adult SOT patients were diagnosed with COVID-19. Of these 54 patients, 36 (67%) patients were eligible for treatment with COVID-19 MABs (casirivimab-imdevimab [n = 25] and bamlanivimab [n = 11]) and 18 were not eligible (15 were either asymptomatic or had symptom duration >10 d, 3 were hospitalized in other facilities because of COVID-19). Here we present our early experience with use of casirivimab-imdevimab in 25 adult SOT patients (17 kidney, 2 liver, 3 heart, and 2 heart/kidney) with at least 14-day follow-up postinfusion (Table 1). At the time of infusion, patients had an average 2.5 (1–7) days of symptoms and none of the patients required supplemental oxygen or hospitalization from COVID-19. They had multiple other risk factors for progression of disease including age >65 years (4 of 25), diabetes (11 of 25), chronic cardiac disease (14 of 25), and chronic kidney disease (11 of 25). Patients were followed for an average of 41 (14–69) days. Other interventions included lowering/stopping mycophenolate (50%) and lowering the dose of calcineurin inhibitor (20%). The only clinical complication observed was secondary bacterial pneumonia in 1 patient, which was successfully treated with a 7-day course of antibiotic therapy. In our experience, of the 25 SOT recipients with mild-moderate COVID-19 who were treated with casirivimab-imdevimab, none experienced progression of symptoms or required hospitalization due to COVID-19. These encouraging early results may be a result of various factors besides treatment with casirivimab-imdevimab alone. During the latter part of our COVID experience, management of these patients has evolved with quicker access to diagnostic tests, a rapid notification process, and the ability to intervene very early in the disease process by offering treatment with MAB to our eligible high-risk patients. Further conclusions regarding the efficacy of casirivimab-imdevimab await the outcomes of well-designed, randomized studies. TABLE 1. - Characteristics of solid organ transplant recipients treated with carisivimab-imdevimab Age (y), mean (range) 50 (24–70) Sex (male) 16 (64%) Kidney transplant 17 (68%) Liver transplant 3 (12%) Heart transplant 3 (12%) Heart-kidney transplant 2 (8%) Time from transplant (mo), mean (range) 186 (10–709) Body mass index (kg/m2), mean (range) 29 (23–36) Duration of symptoms (d), mean (range) 2.5 (1–7) Fever 16 (64%) Malaise 12 (48%) Cough 9 (36%) Nausea/diarrhea 5 (20%) Shortness of breath 4 (16%) Headache 5 (14%) Nasal stuffiness 3 (12%) Oxygen saturation on room air, range 92%–100% Chest x-ray (n = 12) Clear: 4, infiltrates: 8 Follow-up period (d), mean (range) 41 (14–69) Progression of coronavirus disease 0%

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