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Immune Response Muted in Patients With NHL/CLL Who Are Vaccinated Against COVID-19

July 26, 2022

August 2022

Ruth Jessen Hickman, MD

Ruth Jessen Hickman, MD, is a freelance medical and science writer based in Bloomington, Indiana.

Because patients with non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL), a subtype of NHL, have both a higher risk of poor outcomes from COVID-19 and immune system defects as a result of their therapy and cancer itself, scientists have been eager to study the immune response in such patients after vaccination. A study published in Journal of Clinical Oncology adds new information to this literature, finding that such patients’ antibody binding and neutralization against the original SARS-CoV-2 virus and variants such as Delta and Omicron were substantially lower compared to healthy vaccinees.

Given the rapidity of developments in the area, Andres Chang, MD, PhD, of Winship Cancer Institute at Emory University School of Medicine in Atlanta, and colleagues conducted a prospective observational study to look at immune response in this population.

“The prospective nature of the study allowed us to assemble our patient cohort, collect their clinical data, and test the patient samples soon after acquiring them, almost in real time,” Dr. Chang said.

The single-center study included 121 patients with NHL/CLL, 53% of whom had received the Pfizer mRNA vaccine, while the rest had received the Moderna mRNA vaccine. Most had previously received lymphoma-directed therapies, and 47% had received an anti-CD20-directed therapy within the year before their first vaccine dose. A cohort of healthy vaccinees who also received two doses of mRNA vaccine (n=45) was included in the study as a control.

The team employed a multiplex-type assay, which allowed them to efficiently assess several antibodies at the same time. Unlike many other studies of COVID-19, the team also employed a live-virus neutralization assay, allowing them to assess the extent to which antibodies were truly able to neutralize the virus.

After two doses of mRNA vaccine, 67.3% of vaccinated (but not previously infected) patients with NHL/CLL achieved immunoglobulin G (IgG) seroconversion compared to 100% of healthy, vaccinated controls. Patients with NHL/CLL had an 85-fold reduction in mean IgG-binding titers against the spike protein, with significant decreases against other viral components as well. IgA and IgM binding titers were also substantially lower. Antibodies peaked after the second vaccine dose and slowly decreased over time, but peak antibody response and mean antibody level remained significantly lower in patients with NHL/CLL compared to controls.

Antibody binding titers were reduced four-fold in the Delta variant compared to the original Wuhan SARS-CoV-2 strain. Moreover, of patients with detectable neutralizing titers, only 70% had any detectable titers against Delta, and these were six-fold lower compared to healthy controls. With Omicron, only 33% of patients not previously infected had detectable levels of neutralizing antibodies after vaccination, with a 42-fold decrease in titers.

These results were not identical in all subgroups. Patients who were older than 65 had a 10-fold lower total antibody level compared to younger patients. Additionally, patients who had received B-cell depleting therapies against CD20 within a year before their initial vaccination showed a 109-fold reduction in IgG levels compared to those who had received such therapy more than a year before, and a 136-fold reduction compared to those who had never received such therapy. However, some patients who did not mount any detectable antibody response had never received such therapy or had received it more than a year before their vaccination. Moreover, patients with a higher number of circulating B cells had higher IgG levels against the spike protein, suggesting that the rate of peripheral B-cell recovery after therapy correlated with antibody response.

A potentially important caveat is that antibody response is not the body’s only defense mechanism. These vaccines are thought to also elicit a T-cell response, not examined in the current study, which may also confer some protection against COVID-19 disease. Such studies are currently underway. Dr. Chang pointed out that follow-up work is also needed to study the immune response in patients who have received an additional mRNA booster and in vaccinated patients who become infected.

Limitations of the study included that the healthy control cohort was not matched for race and age and the percentage of non-Black minorities and patients with less common NHLs was small among the patient group.

Dr. Chang said, “Overall, our findings stress the importance of performing further studies to understand the immune responses in patients with lymphoma while prioritizing antivirals and passive immunization measures to protect this population.” 

Any conflicts of interest declared by the authors can be found in the original article.


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 [published online ahead of print, 2022 Apr 18]. J Clin Oncol. doi: 10.1200/JCO.22.00088.


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