Patients with lymphoma on active anticancer therapy demonstrated impaired humoral immune response to COVID-19 vaccination, although improved antibody responses were observed with a booster dose, according to the results of prospective observational study published in the Nature Cancer.

“Our results emphasize the urgency of careful monitoring of COVID-19-specific immune responses to guide vaccination schemes in these vulnerable populations,” the authors wrote in their report.

Prior studies suggest that patients with lymphoid malignancies fail to produce detectable levels of antibodies after COVID-19 vaccination. T cell responses to vaccination in this population is not well known. The aim of this study was to characterize vaccine responses, including robustness and persistence, among patients with lymphoma.

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The prospective, observational, multicenter PROSECO study enrolled 457 patients with lymphoma between March and September 2021. All participants received 2 to 3 doses of COVID-19 vaccines after enrollment. Blood samples were taken before vaccination, 4 weeks after their first dose, 2 to 4 weeks after their second dose, and again 24 weeks after their second dose. For patients who received a third dose, blood samples were obtained 6 weeks before and then 4 to 8 weeks after.

The cohort included patients with Hodgkin lymphoma (HL; median age, 40), aggressive B-cell non-Hodgkin lymphoma (NHL; median age, 67), indolent B-cell NHL (median age, 67), and peripheral T-cell lymphoma (PTCL; median age, 63).  The COVID-19 vaccines administered were ChADOx1 (62%) or BNT162b2 (37%).

There were 55% of patients with HL on active treatment, which was most commonly chemotherapy. There were 32% and 38% of patients with aggressive or indolent B-cell NHL, respectively, on treatment that primarily included anti-CD20 antibody plus chemotherapy, or BTK inhibitors for patients with indolent disease. The 31% of patients with PTCL on active therapy received chemotherapy, a PI3K inhibitor, brentuximab vedotin, or ciclosporin.

Patients undergoing active anticancer treatment demonstrated an impaired humoral response, as 52% demonstrated no detectable antibodies to 2 doses of COVID-19 vaccines compared with 8.7% of patients who were not on active therapy. An increased risk of no detectible anti-S IgG was significantly associated with receiving active anticancer therapy (odds ratio [OR], 7.22) or having been treated with an anti-CD20 therapy within the last 12 months (OR, 5.60) in a multivariate analysis.

This impaired humoral response was primarily observed in patients with B-cell NHL, with undetectable antibody levels among 56.8% and 62.7% of patients with aggressive or indolent disease, respectively, compared with 11.1% of patients with HL. The treatment effect could not be analyzed among patient with PTCL due to a small sample size.

COVID-19 vaccination within 3 weeks before or within 5 months after stem cell transplant was also associated with an impaired antibody response compared with patients who received their vaccines 12 months before or after their transplant.

Antigen-specific T-cell response, however, was not significantly affected by anticancer treatment, and was observed for 63% of the cohort after 2 doses of the COVID-19 vaccine.

Although a third vaccine dose improved antibody response among most patients not currently receiving anticancer treatment, 29% still demonstrated low anti-S IgG levels.  A third dose within 52 weeks of receiving anti-CD20 treatment resulted in only 17% of patients developing an improved antibody response. However, a third dose improved antibody response among 75% of patients taking a BTK inhibitor and 100% taking venetoclax.

The authors concluded that “we have demonstrated that the strongest predictor of antibody response in a large cohort of participants with lymphoid malignancies is the timing of treatment in relation to vaccination, regardless of the number of doses administered.”

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


Lim SH, Stuart B, Joseph-Pietras D, et al. Immune responses against SARS-CoV-2 variants after two and three doses of vaccine in B-cell malignancies: UK PROSECO study. Nat Cancer. Published online March 24, 2022. doi: 10.1038/s43018-022-00364-3