P1572: covid-19 mortality in high-risk patients after allo-hsct and car-t: improved outcome through a pandemic.

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: Patients with haematologic malignancies treated with allogeneic stem cell transplantation (HSCT) or chimeric antigen receptor T (CAR-T) cell therapy who experienced SARS-CoV-2 infection during the omicron wave showed to have considerably higher mortality rates compared to immunocompetent patients with omicron infection. Nevertheless, case fatality rates among high-risk COVID-19 patients decreased throughout the pandemics in conjunction with the improvement of prevention policies as well as the rise of more efficient treatments. Aims: Our aim is to highlight how the optimization of a combined system of prophylactic and therapeutic strategies impacts the outcome of omicron infection in a group of patients with high-risk for severe COVID-19. Methods: We prospectively analysed clinical data from a cohort of patients (n=81) who underwent cell therapy and were infected with omicron variant of SARS-CoV-2 between January and November 2022, for a total of 88 cases. All patients were referred to a COVID-19 dedicated outpatient clinic or to general practitioners and were closely monitored within a standardized post-transplant follow-up. Results: We observed 88 SARS-CoV-2 infections in 81 patients, of which 68 experienced mild or moderate symptoms, while thirteen were complicated with interstitial pneumonia, which in six cases required hospitalisation. Median duration of symptoms was 5-7 days while the median time of positivity was 3-4 weeks. Notably, we recorded 9 cases of long-term positivity (>4 weeks), among which 2 cases overcame 12 weeks of positive tests. Remarkably, 7/9 of these patients had a history of chronic GvHD and 1/9 had persistent B cell aplasia after CAR-T cell therapy. We recommended mRNA SARS-CoV-2 vaccination to all patients from the third month after HSCT and from the sixth month after CAR-T cell therapy, according to ECIL-7 and ECIL-9 guidelines: in our cohort, 57 patients had received at least 1 dose of vaccine after cell therapy, while in 24 patients no dose of vaccine was administered after HSCT; among them, 19 patients were not eligible for vaccination, while 5 patients refused vaccination. Furthermore, starting from April 2022, prophylaxis was improved with the administration of Tixagevimab-Cilgavimab to all patients treated with HSCT or CAR-T cell therapy. All patients were classified at high risk for severe COVID-19 according to AIFA (Italian Medicines Agency) indications, thus being eligible to antiviral drugs: 19 patients received Nirmatrelvir/Ritonavir, while a course of Remdesivir was administered to 21 patients. Fourteen patients received infusion of monoclonal antibodies: 12 received Sotrovimab, one patient received Casivirimab/Imdevimab and one Bamlanivimab/Etesevimab. Eventually, 22 patients did not receive any specific treatment. Thirteen patients received a combined treatment. Overall, 4 patients (4.9%) died while positive for SARS-CoV-2: among them, three died for disease progression, while one died for infective complication and concomitant GvHD and poor graft function. Summary/Conclusion: Our experience during the omicron wave confirms the decrease of case fatality rate among a cohort of patients who are intrinsically at higher risk of infection-related mortality. In this setting, we underline the paramount role played by a combination strategy based on both prevention, through prophylactic measures such as individual-level prevention steps, vaccines and monoclonal antibodies, as well as a dedicated hospital organization, and treatment as a key to further implement the outcomes of COVID-19 (figure 1).Keywords: CAR-T, COVID-19, HSCT