1156 - Real-world Effectiveness and Safety of Tixagevimab/Cilgavimab Lower Dosage Regimen in Pre-Exposure Prophylaxis in Patients Undergoing Treatment for Chronic Lymphocytic Leukemia

Introduction: The global health crisis initiated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since 2019 has predominantly affected vulnerable patient populations, including those with chronic lymphocytic leukemia (CLL) due to their advanced age, comorbidities and complex immune impairment. Low rates and duration of antibody responses to the SARS-CoV-2 vaccines have been observed mainly in older patients with hypogammaglobulinemia treated with anti-CD20 monoclonal antibodies and/or targeted oral inhibitors. Consequently, the introduction of a fixed combination of long-acting monoclonal antibodies, tixagevimab/cilgavimab (T/C) neutralising SARS-CoV-2 in pre-exposure prophylactic strategy demonstrated efficacy prior the emergence of the Omicron variant. Omicron variant pandemic surge has been associated with a milder course of COVID-19 disease and a decline in hospitalization and fatality rates in general population; however older immunocompromised patients with comorbidities still warrant prophylactic and early treatment approach.

Objectives: This single-centre retrospective study aimed to examine the effectiveness and safety of T/C in prevention of SARS-CoV-2 infection mitigation of severe course of COVID-19. We included all patients with CLL fulfilling the IWCLL criteria who were undergoing CLL treatment and received T/C at approved dose 150/150 mg every 6 months at a tertiary hematology centre in the Czech Republic. Prophylactic administration was offered to all patients undergoing treatment for CLL. We performed statistical analyses with the SPSS software (version 25.0). Kaplan–Meier curves were used to evaluate time to COVID-19.

Results: A total of 81 consecutive patients on active treatment of CLL who received pre-exposure prophylaxis with T/C from April 8, 2022 to December 15, 2022 with prevailling Omicron variant were included in this study. Fourteen (17%) patients received a follow-up prophylactic dose of T/C 150/150 mg after six months from initial administration. The median age at T/C administration was 71 years (range 42–90), and 44 (54%) were men. Regarding prognostic characteristics, we observed an unmutated immunoglobulin heavy chain variable region gene (IGHV) in 57/78 (73%) patients. Del(17p) and/or TP53 mutation were detected in 20 (25 %). Full details of baseline demographic and clinical characteristics are presented in Table 1.

At the median follow-up of 47 weeks, 31 (38%) patients acquired SARS-CoV-2 infection despite T/C prophylactic administration. Fig. 1 depicts the time to COVID-19 after the first dose of T/C. Notably, in our cohort no patients died as a result of SARS-CoV-2 infection nor were admitted to the intensive-care unit; 8 (10%) patients were hospitalized at a standard ward, and 5 (6%) patients required oxygen therapy. The majority of patients (90%) received at least one dose of anti-SARS-CoV-2 vaccine. T/C intramuscular administration was tolerated well. Only 1 (1 %) patient on ibrutinib reported red skin nodules five days post T/C prophylaxis. This minor adverse event was successfully managed with topical treatment, and importantly, it did not reoccur in subsequent T/C administration.

Conclusion: Our data show that T/C 150/150 mg failed to prevent COVID-19 in about a third of patients during CLL treatment. However, most CLL patients who developed COVID-19 after prophylactic T/C had a mild infection with a low hospitalization rate. We will present updated results, including a comparison with CLL patients who did not receive prophylaxis with T/C. Additionally, we will evaluate the impact of different CLL treatment regimens on the T/C effectiveness.