Patients with B-cell non-Hodgkin lymphoma (B-NHL) who are actively undergoing treatment with an anti-CD20 antibody have an impaired response to the BNT162b2 mRNA (by Pfizer-BioNTech) COVID-19 vaccine, according to research published in Blood Advances.

Patients with B-NHL are at increased risk of developing severe COVID-19, but responses to the vaccine may vary based on treatment. The study authors sought to determine a vaccine strategy for these patients, based on a sample population in Tel Aviv Sourasky Medical Center.

The study included 149 patients with B-NHL; 80 had indolent (i-B-NHL) and 69 had aggressive B-NHL (a-B-NHL). A total of 19% of patients (n=28) were treatment-naïve, 37% (n=55) were actively treated with a rituximab/obinutuzumab (R/Obi)-based induction regimen or maintenance, and 44% (66) had completed treatment with R/Obi more than 6 months before being vaccinated.

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A total of 73 patients (49%) achieved an antibody response to the COVID-19 vaccine, which compared with 98.5% of healthy controls (P <.001). Of the patients undergoing treatment with R/Obi, 10.3% had an antibody response to the vaccine, while 0% of patients on maintenance therapy had a response.

Treatment-naïve patients had a response rate of 89.3% and patients who had completed treatment at least 6 months before vaccination had a 66.7% response rate. Seropositivity increased with time after last exposure to R/Obi therapy.

Control participants without B-NHL had higher antibody titers (mean titer, 1332 ± 1111 U/mL) when compared with the B-NHL cohort (440 ± 1124 U/mL; P <.001).

Patients who had any exposure to anti-CD20 therapy were less likely to have a response to the COVID-19 vaccine. Patients with an absolute lymphocyte count (ALC) ≤0.9 X 103 µ/L were also less likely to respond to the vaccine.

Overall, patients receiving active or maintenance treatment with R/Obi are not likely to develop a humoral response to the mRNA COVID-19 vaccine. 

A limitation of the study is that it focused on humoral response, but did not evaluate the attainment of cellular immune response. Prior research has found that in patients with NHL who were infected with COVID-19, the T-cell response was generally preserved, even in patients who had recently been exposed to B-cell-depleting agents.

The authors recommended that patients with B-NHL who have been treated with anti-CD20 antibody therapy within 2 years should verify their serological response to the COVID-19 vaccine.


Perry C, Luttwak E, Balaban R, et al. Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with B-cell non-Hodgkin lymphoma. Blood Adv. 2021;5(16):3053-3061. doi:10.1182/bloodadvances.2021005094