Anti-SARS-CoV-2 antibody-containing plasma improves outcome in patients with hematologic or solid cancer and severe COVID-19: a randomized clinical trial

Abstract: nature cancer Article https://doi.org/10.1038/s43018-022-00503-w Anti-SARS-CoV-2 antibody-containing plasma improves outcome in patients with hematologic or solid cancer and severe COVID-19: a randomized clinical trial Received: 16 September 2022 A list of authors and their affiliations appears at the end of the paper Accepted: 29 November 2022 Published online: xx xx xxxx Check for updates Patients with cancer are at high risk of severe coronavirus disease 2019 (COVID-19), with high morbidity and mortality. Furthermore, impaired humoral response renders severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines less effective and treatment options are scarce. Randomized trials using convalescent plasma are missing for high-risk patients. Here, we performed a randomized, open-label, multicenter trial (https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001632-10/DE) in hospitalized patients with severe COVID-19 (n = 134) within four risk groups ((1) cancer (n = 56); (2) immunosuppression (n = 16); (3) laboratory-based risk factors (n = 36); and (4) advanced age (n = 26)) randomized to standard of care (control arm) or standard of care plus convalescent/vaccinated anti-SARS-CoV-2 plasma (plasma arm). No serious adverse events were observed related to the plasma treatment. Clinical improvement as the primary outcome was assessed using a seven-point ordinal scale. Secondary outcomes were time to discharge and overall survival. For the four groups combined, those receiving plasma did not improve clinically compared with those in the control arm (hazard ratio (HR) = 1.29; P = 0.205). However, patients with cancer experienced a shortened median time to improvement (HR = 2.50; P = 0.003) and superior survival with plasma treatment versus the control arm (HR = 0.28; P = 0.042). Neutralizing antibody activity increased in the plasma cohort but not in the control cohort of patients with cancer (P = 0.001). Taken together, convalescent/vaccinated plasma may improve COVID-19 outcomes in patients with cancer who are unable to intrinsically generate an adequate immune response. The coronavirus disease 2019 (COVID-19)-associated risk of death is particularly high for patients with hematologic or solid cancer1–3, advanced age4,5 and other conditions6,7. Both humoral8 and cellular9 immunodeficiency contribute to unfavorable outcomes. Despite this, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine availability and waning vaccine efficacy in these patients remain concerning10,11. Few therapies improve outcomes in severe COVID-19 with impaired oxygenation12. Monoclonal antibodies as pre- or postexposure prophylaxis or as early treatment can reduce the risk of severe COVID-19 (refs. 13,14). Evidence for the benefit of monoclonal antibodies in patients requiring oxygen supplementation is missing15 or pending16. e-mail: Claudia.Denkinger@uni-heidelberg.de; carsten.mueller-tidow@med.uni-heidelberg.de Nature Cancer Article https://doi.org/10.1038/s43018-022-00503-w Randomized (n = 134)a Allocation Allocated to plasma (n = 68) - All received the allocated intervention (n = 68) Allocated to standard of care (n = 66) - All received the allocated intervention (n = 66) Follow-up Lost to follow-up (n = 10)b - At day 14 (n = 1) - At day 28 (n = 2) - At day 56 (n = 2) - At day 84 (n = 5) Lost to follow-up (n = 4)b - At day 14 (n = 1) - At day 56 (n = 3) Discontinued intervention (received only one infusion of..