Sipavibart (AZD-3152), a COVID-19 Pre-Exposure Prophylaxis in Myeloma Treated with BCMA/CD3 Bispecific Antibodies
Authors: Gardeney Helene , Bobin Arthur , Gombert Jean-Marc , Herbelin Andre , Tomowiak Cecile , Dindinaud Elodie , Basle Caroline , Nsiala Laly , Cailly Laura , Vonfeld Mathilde , Chacon Aurelia , Pichon Aurelien , Lombard Thomas , Princet Isabelle , Leveque Nicolas , Leleu Xavier , Systchenko Thomas 
Published: December 2024

Background. Bispecific antibodies BCMA/CD3 (BsAbs) increase the risk of developing infections related to the T-cell redirecting function in Multiple Myeloma (MM). Indeed, severe COVID-19 infections were observed despite repeated COVID-19 vaccine doses. COVID-19 targeting monoclonal antibodies, such as tixagévimab/cilgavimab, have effectively prevented COVID-19 in immunocompromised patients, but the emergence of new variants impaired their use.
Sipavibart (AZD-3152) is an investigational long-lasting monoclonal antibody designed to provide COVID-19 coverage including new variants, currently investigated in the phase III SUPERNOVA trial (NCT05648110). The MM treated with BCMA/CD3 BsAbs were excluded from the study due to the systematic intravenous immunoglobulin replacement therapy (IgIV).
We report for the first time the safety and efficacy of Sipavibart for pre exposure prophylaxis (Prep) of COVID-19 in MM treated with BCMA/CD3 BsAbs.
Methods. We collected data from MM patients treated with BCMA/CD3 BsAbs and that received Sipavibart in February and March 2024 in Poitiers University Hospital, France, in the context of the early access authorization for Sipavibart as a COVID-19 pre-exposure prophylaxis in immunocompromised patients.
Results. A total of 19 MM were included in our study with a median age of 64 years old (range 45 - 84). All patients received monthly IgIV. Eighteen (95%) presented at least one comorbidity including chronic kidney disease, cardiovascular disease, diabetes mellitus, obesity or respiratory disease. Median number of prior mRNA COVID-19 vaccine doses was 5 (range 0 - 7) and 3 (16%) patients had a previous PreP treatment with tixagévimab/cilgavimab. Nine patients (47%) had a prior history of COVID-19 infection, including one (5%) severe infection.
The median of prior lines for MM was 2 (range 1 - 7) with 16 (84%) MM treated with ASCT and 2 (11%) with CAR-T cells. Thirteen (68%) were treated with Elranatamab, 6 (32%) were treated with Teclistamab and 4 (21%) had an anti CD38 monoclonal antibody in combination with the BCMA/CD3 BsAbs. With a median time from start of BCMA/CD3 BsAb to Sipavibart injection of 1,3 years (0,7 - 2,1) and a median BCMA/CD3 BsAb pace of 28 days (7 - 56), 11 (58%) MM were in CR or better, 7 (37%) inVGPR and 1 (5%) in PR.
All patients presented hypogammaglobulinemia (median of 4.6 g/L, range 1.5 - 7.7) with immuoparesis. Most patients had also lymphopenia with a median of 0.53 x109/L (range 0.17 - 4.52) related to a systematic CD19 deficit (100%) but also a CD4 deficit (88%), CD8 deficit (38%) or/and NK deficit (59%). All patients presented anti-S and anti-N positive serology that is not protective towards new variants.
After a median follow-up of 113 days (84 -120), no adverse event related to the Sipavibart injection were recorded especially no injection-site reaction, anaphylaxis and cardiovascular adverse events. Only one episode of non-severe COVID-19 infection was reported but with persistent symptoms.
Conclusion. Sipavibart is well tolerated and appears effective in PreP treatment in MM treated with BCMA/CD3 BsAb, patients that are severely immunocompromised. This data needs confirmation in larger study of these MM patients who are severely immunocompromised and at high-risk of severe COVID-19 infections.