Aimwipa Sasakul’s research while affiliated with Chulabhorn Royal Academy and other places

Title: Efficacy of Monoclonal antibody Tixagevimab/Cilgavimab for prevention of SARS-CoV-2 infection among cancer patients : Double blined Randomized placebo Controlled trail (ProvMAB trial) Introduction Immunocompromised patients, particularly those with a Hematological malignancies or Oncologic malignancies, are at higher risk of SARS-Cov-2 infection, severe outcomes and mortality. Tixagevimab/Cilgavimab is a monoclonal antibody combination which binds to the SARS-CoV-2 spike protein. The PROVENT phase III clinical trial reported that Tixagevimab/Cilgavimab prophylaxis significantly reduced the risk of COVID-19 infection in immunocompromised participants who had not been vaccinated prior to enrollment. However, it should be noted that this trial was conducted before the emergence of the Omicron variant. While the approved Tixagevimab/Cilgavimab combination has demonstrated the ability to decrease the rate of symptomatic SARS-CoV-2 infection in patients at higher risk of inadequate response to vaccination. However, Tixagevimab/Cilgavimab was tested in a few studies that included patients with hematologic malignancies and oncologic malignancies, even if this population has shown an increased risk of unfavorable outcomes following infection (with high rates of hospitalization, intensive care unit admission, and mortality) and poor significant immunization following vaccines. Method We performed a randomized clinical trial double blind study to evaluate the rate of SARS-CoV-2 infection following pre-exposure prophylaxis with Tixagevimab/Cilgavimab 150/150 mg versus placebo in Hematologic malignancies and Oncologic malignancies patients who were on active treatment with systemic chemotherapy within 6 months. These patients received at least three doses of vaccination before enrollment, and neutralizing antibody and anti-spike antibody levels were measured at day 0, day 30, day 90 and day 180 after enrollment. The study was started from September 7, 2022, until July 19,2023, with a follow-up period of 180 days for all cases. Result A total of 138 participants were recruited, with 68 patients in the intervention arm and 70 patients in the placebo arm. The mean age in the intervention arm was 58 years old, while it was 59 years old in the placebo arm. The cumulative incidence of Covid-19 infection was 7.4% in intervention arm compared to 7.15% in the placebo arm (HR= 1.04; 95% CI :0.3 to 3.58, p-value=0.956). Covid-19-related-hopitalizations were 5.9% of the intervention arm and 1.4% of the placebo arm. No patients need to admit ICU in both arms. No deaths due to Covid-19 infection were reported during the study. Discussion In this study, we present our findings comparing Tixagevimab/Cilgavimab in immunocompromised patients who received over three doses of vaccination for the prevention of SARS-CoV-2 infection in patients with hematologic malignancies and Oncologic malignancies undergoing chemotherapy during the SARS-CoV-2 omicron surge. Our results suggest that booster vaccinations, beyond the standard three doses, were sufficient to protect against SARS-CoV-2 infection in this particular patient population, considering their ongoing standard of care during the pandemic variant in the future. Keywords: SARS-CoV-2, COVID-19, Tixagevimab/Cilgavimab, Hematological malignances, monoclonal antibodies

Purpose: The present study aimed to study the immunogenicity of the ChAdOx1 nCoV-19 vaccine in patients with hematologic malignancies. Materials and methods: This prospective cohort study of hematology patients aimed to evaluate their antibody levels against the receptor-binding domain of the severe acute respiratory syndrome coronavirus 2 spike protein and seroconversion rates following two doses of the ChAdOx1 nCoV-19 vaccine. Between June and July 2021, we enrolled 61 patients and included 44 patients in our analysis. Antibody levels were assessed 8 and 4 weeks after the first and second injections, respectively, and compared with those of a healthy group. Results: Eight weeks after the first dose, the geometric mean antibody level was 1.02 binding antibody units (BAU)/mL in the patient group and 37.91 BAU/mL in the healthy volunteer group (p<0.01). Four weeks after the second dose, the geometric mean antibody level was 9.44 BAU/mL in patients and 641.6 BAU/mL in healthy volunteers (p<0.01). The seroconversion rates 8 weeks after the first dose were 27.27% and 98.86% in the patient and healthy volunteer groups, respectively (p<0.001). The seroconversion rate 4 weeks after the second dose was 47.73% in patients and 100% in healthy volunteers. Factors leading to lower seroconversion rates were rituximab therapy (p=0.002), steroid therapy (p<0.001), and ongoing chemotherapy (p=0.048). Factors that decreased antibody levels were hematologic cancer (p<0.001), ongoing chemotherapy (p=0.004), rituximab (p<0.001), steroid use (p<0.001), and absolute lymphocyte count <1,000/mm3 (p=0.009). Conclusion: Immune responses were impaired in individuals with hematologic malignancies, particularly patients undergoing ongoing therapy and B-cell-depleting therapy. Additional vaccinations should be considered for these patients, and further investigated.