Humoral Responses Against SARS-CoV-2 and Variants of Concern After mRNA Vaccines in Patients With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia

Abstract

PURPOSE Patients with non-Hodgkin lymphoma including chronic lymphocytic leukemia (NHL/CLL) are at higher risk of severe SARS-CoV-2 infection. We investigated vaccine-induced antibody responses in patients with NHL/CLL against the original SARS-CoV-2 strain and variants of concern including B.1.167.2 (Delta) and B.1.1.529 (Omicron). MATERIALS AND METHODS Blood from 121 patients with NHL/CLL receiving two doses of vaccine were collected longitudinally. Antibody binding against the full-length spike protein, the receptor-binding, and N-terminal domains of the original strain and of variants was measured using a multiplex assay. Live-virus neutralization against Delta, Omicron, and the early WA1/2020 strains was measured using a focus reduction neutralization test. B cells were measured by flow cytometry. Correlation between vaccine response and clinical factors was determined. RESULTS Mean anti-SARS-CoV-2 spike immunoglobulin G–binding titers were 85-fold lower in patients with NHL/CLL compared with healthy controls, with seroconversion occurring in only 67% of patients. Neutralization titers were also lower and correlated with binding titers ( P < .0001). Treatment with anti-CD20-directed therapies within 1 year resulted in 136-fold lower binding titers. Peripheral blood B-cell count also correlated with vaccine response. At 3 months from last anti-CD20-directed therapy, B-cell count ≥ 4.31/μL blood around the time of vaccination predicted response (OR 7.46, P = .04). Antibody responses also correlated with age. Importantly, neutralization titers against Delta and Omicron were reduced six- and 42-fold, respectively, with 67% of patients seropositive for WA1/2020 exhibiting seronegativity for Omicron. CONCLUSION Antibody binding and live-virus neutralization against SARS-CoV-2 and its variants of concern including Delta and Omicron were substantially lower in patients with NHL/CLL compared with healthy vaccinees. Anti-CD20-directed therapy < 1 year before vaccination and number of circulating B cells strongly predict vaccine response.

Response of COVID-19 vaccination in multiple sclerosis patients following disease-modifying therapies: A meta-analysis

“…Emerging evidence from patients with hematologic malignancies and other immune-mediated inflammatory disorders also indicated that anti-CD20 therapy was correlated with the risk of serological negative responses after completed vaccination against SARS-CoV-2, which were in line with our finding. 23 , 24 In consideration of potential influences of molecular structure of the substances, immunological effects and pharmacokinetics of different drugs, we performed subgroup analysis by the types of anti-CD20 antibodies. We found no statistical difference in seroconversion rate between MS patients treated with rituximab and ocrelizumab.…”

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“… [4] , [5] , [6] Despite these factors potentially being reassuring for blood cancer patients, concern remains, particularly in light of observations regarding suboptimal protection from COVID-19 vaccines in this group. [7] , [8] This present study aimed to compare the outcome of hemato-oncology patients at Barts Cancer Centre diagnosed with COVID-19 during recent months with our previous cohort at the start of the pandemic. We aimed to determine whether the lower mortality and risk of hospital admission seen in the general population, associated with newer variants, anti-COVID therapies and widespread vaccination, is reflected in patients with hematological malignancies.…”

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“…However, the emergence of the Omicron (B.1.1.529) variant which was discovered in November 2021 and then spread quickly globally, the situation changed. Omicron, with its extensive mutations in neutralizing epitopes, is able to at least partially evade in vitro neutralizing antibodies induced by 3 rd doses in patients with cancer [31,32]. The potential utility and timing of a 4 th COVID-19 vaccine dose has been brought up especially for those who are at risk for poor seroconversion after 3 rd doses [33], with the Centers for Disease Control (CDC) recommending 2 additional boosters following a 3-vaccine primary series [34].…”