P1558: prophylaxis with tixagevimab-cilgavimab in single-center experience can reduce severe complications related to sars-cov-2 infection in hematological patients

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: In 2021, the worldwide development of anti-COVID-19 messenger RNA vaccines radically changed and revolutionized the approach to the virus, especially for fragile patients. On the one hand, they guaranteed to lower the percentages of patients suffering from a severe form of COVID-19 infection, preventing the worst outcomes and radically reducing related mortality. On the other, they faced cases of patient subsets unable to produce anti-SARS-CoV-2 spike antibodies in response to vaccination. Malignancies (especially hematological), immunodeficiency states, and recent use of B-cell-depleting therapies are well-described clinical conditions capable of preventing an adequate vaccine response. Moreover, significant infection-related mortality (over 10%) in these subgroups of patients has been reported. In this context, preexposure prophylaxis with tixagevimab-cilgavimab (a monoclonal antibody able to avoid attachment of the SARS-CoV-2 spike protein to the surface of cells approved in 2022 by FSA and EMA) has resulted in an alternative strategy, based on the promising results of the phase III PROVENT study. Aims: This retrospective observational report aims to collect the clinical data of patients treated in a single center with prophylactic therapy with tixagevimab-cilgavimab, evaluating the incidence of breakthrough infections and, in infected patients, the severity (potential reduction of severe forms) and the outcome. Methods: Our cohort was based on 202 adult (>18 years) patients affected by active hematological diseases (involving myeloid and lymphoid lineages), undergoing immunosuppressive therapies after hematopoietic stem cell transplantation (HSCT), or undergoing B-cell depleting therapies. All data of the enrolled patients are reported in Table 1. The median observation time (defined as the time from tixagevimab-cilgavimab administration until January 2023) was 194 days [IQR 132-210]. A COVID-19 infection was diagnosed following a positive molecular or antigenic swab. To statistical analysis, a p-value under 0.05 was considered significant. Results: At the end of the observation period, 39 (19.3%) patients experienced breakthrough infection after tixagevimab-cilgavimab prophylaxis, with a median occurrence of 65 days (ranging from 2 to 219 days). The median duration of infection was 11 (4-50) days, with an asymptomatic course/mild symptoms in 30 (76.9%). Only 2 patients (affected by MM, with ongoing anti-BCMA, and DLBCL with anti-CD20 concomitant therapy) reported severe acute respiratory distress requiring hospitalization. Based on the type of treatment, no difference in incidence was found. Conversely, the median time of infection with recent monoclonal antibodies (MoAb) antiCD20 treatment was 25.5 days, statistically higher than other ongoing treatment groups (P=.003) (figure 1). Concerning the underlying hematologic condition, patients affected by MM reported a higher incidence of breakthrough infection, in any case without complications worthy of note. At the end of the observation period, the censored patients were 197 (97.6%) without any death related to SARS-CoV-2 infection. The other data are reported in Table 1. Summary/Conclusion: Tixagevimab-cilgavimab seems to be a useful prophylaxis therapy that can allow passive immunization and warrant long-term protection from severe SARS-CoV-2 disease in categories of patients unable to develop fair antibody responses. Patients subjected to anti-CD20 MoAb therapy confirmed the difficulty in completing a rapid virus clearance due to the impaired B-cell immune system.Keywords: Prophylaxis, Hematological malignancy, COVID-19, Infection