ABSTRACT
Context: Patients with B cell non-Hodgkin lymphoma and chronic lymphocytic leukemia (NHL/CLL) are at increased risk of morbidity and mortality from SARS-CoV-2 infection. Anti-SARS-CoV-2 vaccination is highly recommended for these patients but their antibody responses after the initial vaccination series is impaired, particularly when measured against SARS-CoV-2 variants. Objective: To assess antibody responses against SARS-CoV-2 variants after booster vaccination in NHL/CLL patients. Design: We designed a single center, prospective, observational study and collected blood and clinical data on 69 patients who received an approved booster dose. Antibody binding against SARS-CoV-2 spike of the original strain and of variants of concern were measured using a multiplex assay. Live-virus neutralization against Delta, Omicron, and the ancestral WA1/2020 strains were measured by focus reduction neutralization test (FRNT). Correlation between vaccine response and clinical factors were determined. Results: Median anti-SARS-CoV-2 IgG binding titers were 8.6-fold lower in NHL/CLL patients without prior SARS-CoV-2 infections compared to healthy individuals. IgA and IgM titers were similarly reduced. Among the 51 patients with available pre- and post-booster samples, only 45% achieved a >3.16 fold-increase in IgG titers after booster (median fold increase = 2.58 vs 41.0 for healthy vaccinees). A substantial decrease in IgG binding to variant SARS-CoV-2 spike, particularly from B.1.1.529 (Omicron) variants, was observed. However, reductions were similar to healthy vaccinees (median fold reduction: 4.82 vs 4.83, respectively). Neutralizing antibody titers against WA1/2020 strain were detected in 44% of patients but only 16% of patients had neutralizing antibody titers against Omicron before booster vaccination. Neutralizing titers against WA1/2020 and Omicron were detected in 61% and 43% of patients after booster respectively, though mean titers against Omicron were 11.5-fold lower than WA1/2020. Clinical correlates to vaccine response including treatment status will be presented. Conclusions: Antibody binding and live-virus neutralization titers against SARS-CoV-2 and its variants including Omicron are lower in NHL/CLL patients compared to healthy individuals even after booster vaccination. Our study reinforces the need to prioritize anti-SARS-CoV-2 prophylactic and treatment agents to protect this highly immunosuppressed population. Funding: Winship Cancer Institute and Emory University Institutional Funds, NCI U54 CA260563, P30CA138292, NIH P51 OD011132, HHSN272201400004C, U19AI090023, R35CA197603.