Chang A et al., Humoral Responses Against SARS-CoV-2 and Variants of Concern After mRNA Vaccines in Patients With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia. J Clin Oncol 40: 3020–3031
The study included blood samples from a total of 121 patients with NHL/CLL. These had each received two doses of COVID-19 vaccine (47% Moderna, 53% BioNTech/Pfizer). Healthy vaccine subjects served as a comparison group.
Antibody binding against the spike protein, the receptor-binding and N-terminal domains of the original strain and the two virus variants Delta and Omicron was measured using a so-called multiplex assay.
In another test, the researchers also determined the neutralisation of live viruses of the Delta, Omicron and early WA1/2020 strains by the serum antibodies. In addition, the number of B cells was determined using flow cytometry.
Overall, the results of the study showed that the titres for anti-SARS-CoV-2 spike immunoglobulin G were much lower in NHL/CLL patients compared to the healthy cohort. According to the measurements, the antibody response following COVID-19 vaccination was about 85-fold lower in the leukaemia patients, and seroconversion was also only observed in 67% of the patients.
The same was found for the neutralisation tests. These were also lower in leukaemia patients than in healthy controls. Moreover, treatment with anti-CD20-targeted therapies within one year led to 136-fold lower binding titres in the patients after vaccination.
Likewise, the number of B cells in the peripheral blood correlated with the response to the respective vaccine. Three months after the last anti-CD20 therapy, a B-cell count of ≥ 4.31/ml blood at the time of vaccination predicted response (OR 7.46; p = 0.04). Antibody responses also correlated with age, as expected.
Patients with non-Hodgkin's lymphoma and chronic lymphocytic leukaemia (NHL/CLL) have an increased risk of becoming more severely ill with COVID-19 or dying as a result of infection with SARS-CoV-2. Vaccination against SARS-CoV-2 is therefore strongly recommended for these patients, but the antibody responses achieved after such vaccination have been poorly characterised.
Antibody binding and neutralisation of SARS-CoV-2 wild-type virus and its variants - Delta and Omicron - were significantly weaker in patients with NHL/CLL compared to healthy vaccinated individuals. Anti-CD20 therapy for one year prior to vaccination and a low circulating B-cell count were good predictors of a lower response to the vaccine.
The results of this study highlight the need for people with leukaemic disease to increase response to COVID-19 vaccines through booster doses. In addition, antiviral agents and prophylactic antibody therapies should continue to be made available for severe hospital courses to protect this highly immunocompromised patient group, the researchers conclude.
Chang A et al., Humoral Responses Against SARS-CoV-2 and Variants of Concern After mRNA Vaccines in Patients With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia. J Clin Oncol 40: 3020–3031