Impact of COVID‐19 infection on bispecific antibodies treatment in patients diagnosed with B‐cell lymphoproliferative disorders

Introduction: Bispecific antibodies (BsAbs) are a promising therapeutic approach for the treatment of B-cell lymphoproliferative disorders. Limited data is available regarding the impact of COVID-19 in patients treated with BsAbs. We assessed the impact of COVID-19 infection on BsAbs treatment and evaluated the severity of COVID-19 infection and the seroconversion rate. Methods: Patients treated with BsAbs at our institution were reviewed from March 2020 to January 2023. Severity of COVID-19 infection was defined according to World Health Organization (WHO) criteria. Seroconversion rate was assessed using chemiluminescence immunoassays for the determination of antibodies against SARS-CoV2 spike glycoprotein (cutoff, 40 BAU/mL). Patients who received convalescent plasma, sotrovimab or AZD7442 (cilgavimab and tixagevimab) were excluded from the seroconversion analysis. Results: One hundred and nine patients (median age, 62 years old) were included. Most frequent diagnoses were Diffuse Large B-Cell Lymphoma (73%) and Follicular Lymphoma (18%). Median number of previous lines was 2. Ninety-four patients (86%) received an anti-CD20/CD3, 13 (12%) an anti-CD22/CD3 and 2 (2%) an anti-CD19/4-1-bb. Anti-CD20 agents in the prior 6 months had been administered alone or in combination in 61 patients (56%). Twenty-two (20%) patients had received prior CAR-T cell therapy for a median of 5 months. Eighty-six patients (79%) were vaccinated (in general with Spikevax), with an average of 3 doses. COVID-19 infection was diagnosed in 61 patients (56%); 23 (38%) presented mild COVID-19 infection, 20 (33%) moderate, 11 (18%) severe and 7 (11%) critical. Ten patients were diagnosed with a second COVID-19 episode; of these, sequencing results confirmed a reinfection in 2 patients and a persistent infection in 8 patients. Median time to first negative PCR was 34 days and 62 days for those who presented a second infection. Twenty-five patients became infected during treatment causing 84% delays and 20% discontinuations. At the time of infection, 76% of the patients had negative serology. A higher seroconversion rate was observed in the post treatment setting with BsAbs after a median of 6 months. No differences were evidenced according to recent exposure to an anti-CD20 agent (figure 1D). Patients with positive serology (24%) presented milder infection (p = 0.009). After a median follow up of 34.3 months, 32 patients died (29%), 19 due to progressive disease, 6 from COVID-19 pneumoniae (10%, 5 of which were in complete response), 5 from other infections and 2 of unknown causes. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Immunotherapy, Indolent non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract. A. Serna Consultant or advisory role: Pharmore Research M. Jiménez Honoraria: GSK, Sanofi A. Cabirta Honoraria: Jazz, AstraZeneca, Janssen A. Albasanz Consultant or advisory role: Gilead, GSK Honoraria: Gilead, GSK, Pfizer I. Ruiz-Camps Consultant or advisory role: GSK, AstraZeneca, BMS, MSD, Gilead, Pfizer, Janssen Honoraria: GSK, AstraZeneca, BMS, MSD, Gilead, Pfizer, Janssen T. García Consultant or advisory role: Janssen, Roche, Gilead, Celgene Research funding: Janssen, AbbVie C. Carpio Consultant or advisory role: Regeneron Pharmaceuticals, Takeda Honoraria: Gilead, Novartis, AstraZeneca, BMS S. Bobillo Consultant or advisory role: Janssen, Roche, Gilead Honoraria: Janssen, Roche, Gilead Educational grants: Gilead G. Iacoboni Consultant or advisory role: Novartis, Kite/Gilead, BMS/Celgene Honoraria: Novartis, Kite/Gilead, BMS/Celgene, AstraZeneca, Roche, AbbVie, Janssen, Miltenyi A. Marín-Niebla Consultant or advisory role: Lilly, Kite, Kiowa Kirin, Takeda, AstraZeneca, Roche, Janssen Honoraria: Lilly, Kite, Takeda, Janssen F. Bosch Consultant or advisory role: Novartis, Celgene/BMS, Roche, AstraZeneca, Takeda, Mundipharma, Gilead, AbbVie, Lilly, Beigene Honoraria: Novartis, Celgenes/BMS, Roche, AstraZeneca, Takeda, Karyospharm, Mundipharma, Gilead, AbbVie, Lilly, Beigene P. Abrisqueta Consultant or advisory role: Roche, AbbVie, BMS, AstraZeneca, Janssen, Incyte Honoraria: Roche, Abbvie, BMS, AstraZeneca, Janssen, Sandoz