Antibody responses to COVID-19 vaccines are significantly lower in patients with non-Hodgkin lymphoma (NHL) than in healthy individuals, according to research published in the Journal of Clinical Oncology.

Patients with NHL had significant reductions in binding and neutralizing antibodies against the original SARS-CoV-2 strain, and antibodies against the omicron and delta variants were even lower.

Several factors appeared to affect antibody responses in these patients, including age, time since the last anti-CD20 therapy, and circulating B-cell numbers.

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The study included 121 patients with NHL who received 2 doses of a COVID-19 vaccine. Roughly half of patients (47%) received the Moderna vaccine, and the other half (53%) received the Pfizer-BioNTech vaccine. The median age of the patients was 63.8 years, most were non-Hispanic White, and 59% were men. 

Cancer types included chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL; n=50), other B-cell NHLs (n=67), and T-cell NHLs (n=4). Most patients had received lymphoma-directed therapies, and 47% were treated with anti-CD20-directed therapy within 1 year before the first vaccine dose.

The study also included 45 healthy control individuals who had received 2 doses of an mRNA COVID-19 vaccine.

Response Against Original Strain

The researchers measured immunoglobulin G (IgG)-, IgA-, and IgM-binding antibody responses to the full-length spike protein, the receptor binding domain (RBD), and the N-terminal domain (NTD) of the spike protein of the original SARS-CoV-2 strain.

After 2 vaccine doses, IgG seroconversion occurred in 67% of the NHL patients and 100% of the healthy control individuals.

Compared with the healthy individuals, patients with NHL had an 85-fold reduction in mean IgG-binding titers against the full-length spike protein, a 62-fold reduction in titers against the RBD, and a 46-fold reduction in titers against the NTD. The researchers observed similar decreases in IgA- and IgM-binding titers.

To determine the functionality of the antibodies, the researchers performed a live-virus focus reduction neutralization test in samples from the healthy control individuals and the NHL patients without prior SARS-CoV-2 infection. The team used the WA1/2020 strain of SARS-CoV-2, which closely resembles the original Wuhan strain.

All healthy control individuals developed neutralizing antibodies, compared with 68% of the NHL patients. Furthermore, median neutralizing antibody titers were 4-fold lower in the NHL patients than in the healthy individuals.

Response Against Variants of Concern

The researchers assessed whether antibodies after vaccination recognized the spike proteins of 17 SARS-CoV-2 variants of concern in a subset of the patients with NHL. The median IgG-binding titers were highest against the spike protein of the Wuhan strain and lowest against the beta variant.

The researchers also performed a live-virus focus reduction neutralization test to determine neutralization against the omicron and delta variants in the NHL patients without prior SARS-CoV-2 infection.

Of the patients with detectable neutralizing antibodies against the WA1/2020 strain, 70% had detectable antibodies against the delta variant, and 33% had detectable antibodies against the omicron variant. Neutralizing antibody titers were 6-fold lower against delta and 42-fold lower against omicron.

Factors Tied to Response

Patients with NHL who received anti-CD20-directed therapies within 1 year before their initial vaccination exhibited the greatest impairment in response to vaccination. They had a 136-fold reduction in IgG titers when compared with treatment-naïve patients and a 109-fold reduction when compared with patients whose last anti-CD20-directed therapy was more than 1 year before vaccination. 

There was a correlation between antibody response and peripheral B-cell counts as well. At 3 months from the last anti-CD20-directed treatment to COVID-19 vaccination, a B-cell count of at least 4.31/mL blood was a significant predictor of response (odds ratio, 7.46; P =.035).

The researchers also observed a correlation between antibody responses and age. Patients older than 65 years had a 10-fold reduction in antibody titers, compared with patients who were 65 years and younger (P =.0016).

The researchers concluded that these findings support “recommendations by health authorities on the need for continuing public health mitigations, additional vaccine doses, and early therapy with oral antiviral agents or passive immunization with anti-SARS-CoV-2 monoclonal antibodies to protect this highly immunosuppressed population.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Chang A, Akhtar A, Linderman SL, 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. Published online April 18, 2022. doi:10.1200/JCO.22.00088

This article originally appeared on Cancer Therapy Advisor