Safety and efficacy of SARS-Cov2 neutralizing monoclonal antibodies after stem cell transplant or CAR-T cell infusion

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV2) was responsible for the life‐threatening coronavirus disease 19 (COVID‐19), a worldwide pandemia declared by the WHO in March 2020. COVID‐19 infection has affected hematologic patients more severely than general population, probably due to underlying impaired immunity response, active chemotherapy and immunosuppressive treatment. The Center for International Blood and Marrow Transplant Research (CIBMTR) reported 318 COVID‐19 cases after stem cell transplant (SCT). Moderate and severe disease was documented in 27% and 15% of allogeneic SCT (allo‐SCT) and in 20% and 12% of autologous ones (auto‐SCT). COVID‐19‐related deaths and overall probability of survival at 30 days from COVID‐19 diagnosis were 20% and 68% after allo‐SCT and 14% and 67% after auto‐SCT. Risk factors for COVID‐19‐related mortality were: age >50 years, COVID‐19 diagnosis within 12 months from transplant, lymphocyte count <0.3*109/L and diagnosis of lymphoma. 1 The European Society for Blood and Marrow Transplantation (EMBT) reported data on 56 COVID‐19 infection cases after Chimeric Antigen Receptors T‐cell (CAR‐T). Severe COVID‐19 disease and COVID‐19‐related mortality were registered in 39% and 41% of patients, respectively. Favouring risk factors resulted older age, active underlying disease and metabolic comorbidities. 2 Hematologic patients showed an impaired serological response to SARS‐Cov2 vaccines as compared to healthy people 3 , 4 , 5 and cancer patients, even after completion of the two‐dose cycle of BNT162b2 or mRNA‐1273 vaccine. 6 With particular interest for lymphoproliferative disorder, it is well known that monoclonal antibodies against CD20, 7 , 8 as well as CAR‐T treatment cause deep and prolonged lymphodepletion and hypogammaglobulinemia lasting several months after treatment. 7 , 9 In the allo‐HSCT setting, particularly after myeloablative conditioning, patients resulted at high risk of COVID‐19, obtained lower serological response rate to SARS‐CoV2 vaccines and occasionally showed a prolonged viral shedding. 7 , 9 Therefore, these patients need a strictly monitoring for immunoglobulin level and lymphocyte subsets assessment after cell therapy. Starting from February 2021, the distribution of monoclonal antibody (MoA) casirivimab/imdevimab was authorized in Italy for the treatment of mild to moderate COVID‐19 disease in patients at high risk for developing severe illness. Recently, O’Brein and colleagues shared results from their randomized clinical trial on asymptomatic and seronegative subjects, found to be positive for SARS‐CoV2. Compared to placebo, subcutaneous casirivimab/imdevimab significantly prevented progression to symptomatic disease (29.0% vs. 42.3%), reduced of approximately 5.6‐day the symptoms duration, and reduced the number of high viral load weeks per 1000 participants (489.8 vs. 811.9 weeks