P1513: reduction of the prophylactic effect of tixagevimab-cilgavimab in the omicron era in patients with hematological malignancies and without antibody response following sars-cov-2 vaccination.

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: Pre-exposure prophylaxis against SARS-CoV-2 with tixagevimib-cilgavimib (AZD7442) has become a clinical practice in hematologic centres, especially in patients receiving B-cell depletion or immunosuppressive therapy. However, data regarding AZD7442 specific preventive effect in the onco-hematological population, in the Omicron era, are limited and in the registrative study (PROVENT-NCT04625725) the number of hematologic patients included are not specified and only 7% of participants had cancer. Aims: To evaluate the prophylactic efficacy of AZD7442 (tixagevimib-cilgavimib) in the Omicron era, in patients with hematological malignancies and without antibody response after SARS-CoV-2 vaccination. Methods: Between April 2022 and October 2022, a total of 93 onco-hematologic patients (77 Non Hodgkin Lymphoma or Chronic Lymphocytic Leukemia, 10 Multiple Myeloma, 6 Acute Myeloid Leukemia) with a median age 72 yrs. (range, 27-88) received AZD7442 prophylaxis (150 mg tixagevimib and 150 mg cilgavimib) at Division of Hematology ASUFC-Udine-Italy. All patients had inadequate humoral vaccination response with Ab anti SARS-CoV-2 less than 10 UI/mL in 83% of cases (and less than 100 UI/mL in the other 17%) despite 2 (15%) or ≥ 3 (85%) anti SARS-CoV-2 vaccination doses. Results: No side effects grade CTC ≥ 2 were reported after AZD7442 administration and prophylaxis was very well tolerated. The median value of the anti SARS-CoV-2 spike protein IgG antibodies in blood samples (neutralizing antibody titer), collected after 1 month, 2 months and 3 months from AZD7442 administration, was ≥ 2460 UI/mL, 2416 UI/mL and 2400 UI/mL, respectively. This confirmed an elevated and persistent post-prophylactic antibody levels after AZD7442 administration. Within 6 months of AZD7442 prophylaxis, 20.4% (19/93) of patients developed symptomatic SARS-CoV-2 infection with 5/19 (26%) severe cases (with pneumonia and respiratory failure). The dominant variant in our Region, in the period of this study, was Omicron. The 21% (4/19) of cases with symptomatic infection died from COVID-19 as a primary cause of death. Summary/Conclusion: Prophylaxis against SARS-CoV-2 with tixagevimib-cilgavimib (AZD7442) was well tolerated in hematological patients. However, in the Omicron era, we found that the prophylactic effectiveness of AZD7442 was significantly lower than reported in the registrative study (we reported 20.4% of symptomatic SARS-CoV-2 infection within 6 months of prophylaxis compared to 0,2% cases of registrative study). In addition 4,3% (4/93) of our patient population died from COVID-19 despite AZD7442 prophylaxis. These results underline: 1) the importance to maintain a close monitoring of SARS-CoV-2 infection in onco-hematological patients, 2) the need to promptly start a specific therapy in this patient population and 3) the need to update the prophylactic antibody mixtures according to the new prevalent SARS-CoV-2 variants. Keywords: COVID-19, Lymphoproliferative disorder, Prophylaxis, Infection