Anti-CD20 antibodies and bendamustine attenuate humoral immunity to COVID-19 vaccination in patients with B-cell non-Hodgkin lymphoma

Abstract

Serologic responses of COVID-19 vaccine are impaired in patients with B-cell lymphoma, especially those who had recently been treated with anti-CD20 monoclonal antibodies. However, it is still unclear whether those patients develop an immune response following vaccination. We investigated the efficacy of vaccination against SARS-CoV-2 in 171 patients with B-cell non-Hodgkin lymphoma (B-NHL) who received two doses of an mRNA-based COVID-19 vaccine and we compared the efficacy of vaccination to that in 166 healthy controls. Antibody titers were measured 3 months after administration of the second vaccine dose. Patients with B-NHL showed a significantly lower seroconversion rate and a lower median antibody titer than those in healthy controls. The antibody titers showed correlations with the period from the last anti-CD20 antibody treatment to vaccination, the period from the last bendamustine treatment to vaccination and serum IgM level. The serologic response rates and median antibody titers were significantly different between diffuse large B-cell lymphoma (DLBCL) patients in whom anti-CD20 antibody treatment was completed within 9 months before vaccination and follicular lymphoma (FL) patients in whom anti-CD20 antibody treatment was completed within 15 months before vaccination. Moreover, the serologic response rates and median antibody titers were significantly different among FL patients in whom bendamustine treatment was completed within 33 months before vaccination. We demonstrated that B-NHL patients who were recently treated with anti-CD20 antibodies and bendamustine had a diminished humoral response to COVID-19 vaccination. UMIN 000,045,267.

Prolonged shedding of viable SARS‐CoV‐2 in immunocompromised patients with haematological malignancies: A prospective study

“…Moreover, we demonstrated a decrease in the production of neutralizing antibodies in samples from patients who had received bendamustine therapy. Our previous study showed that B‐cell lymphoma patients who were treated with anti‐CD20 antibodies and bendamustine had a diminished humoral response to COVID‐19 vaccination, 14 consistent with the results of the present study. Therefore, the essential factors that cause prolonged infection are likely to be severe CD4 + T‐cell dysfunction and low neutralization activity, rather than the type of disease.…”

Back to the Future: Immune Protection or Enhancement of Future Coronaviruses

“…In B-cell lymphoma patients treated with rituximab and bendamustine, the humoral immune response (but not the T-cell response) to SARS-CoV-2 vaccination is impaired, as would be expected from a B-cell-depleting treatment [ 28 ]. Similar results were published by Candon et al and Ishio et al [ 29 , 30 ]. Patients with B-cell lymphoma who were successfully treated with rituximab and recovered show normal antibody responses after (mRNA) SARS-CoV-2 vaccines [ 31 ].…”

Initial Efficacy of the COVID-19 mRNA Vaccine Booster and Subsequent Breakthrough Omicron Variant Infection in Patients with B-Cell Non-Hodgkin’s Lymphoma: A Single-Center Cohort Study

“…Especially in the indolent lymphoma group, the decrease in the booster effect was more obvious. One of the reasons may be due to the treatment with bendamustine and ibrutinib [ 24 , 25 , 26 ], which were rarely used for DLBCL at the time of this study. Additionally, it has been reported that patients with indolent B-NHL have longer seroconversion times after vaccination than patients with aggressive B-NHL [ 7 ].…”