# Impaired booster-induced SARS-CoV-2 antibody responses in rituximab-treated B-cell lymphoma patients despite peripheral B-Cell Recovery

**Authors:** Tomaz Jurca, Lucka Boltezar, Miha Orazem, Kristina Fujs Komlos, Katka Pohar, Sara Jevnikar, Mario Poljak, Denis Mlakar Mastnak, Nada Rotovnik Kozjek, Bor Vratanar, Janja Ocvirk, Alojz Ihan

PMC · DOI: 10.2478/raon-2026-0014 · Radiology and Oncology · 2026-03-24

## TL;DR

B-cell lymphoma patients treated with rituximab have weak antibody responses to a booster COVID-19 vaccine, even after B-cell counts return to normal.

## Contribution

This study shows that B-cell recovery does not restore effective antibody responses to boosters in rituximab-treated lymphoma patients.

## Key findings

- Patients on anti-CD20 therapy had no antibody responses to the vaccine.
- Recovered B-cell counts did not lead to normal antibody levels after booster vaccination.
- T-cell responses and adverse events were monitored but not the primary focus of findings.

## Abstract

Rituximab-treated patients with B-cell lymphoma exhibit profound B-cell depletion and impaired vaccine-induced antibody responses. However, it remains uncertain whether recovery of peripheral B-cell counts after rituximab is sufficient to restore effective humoral immunity following booster vaccination.

In this prospective, single-center observational study at the Institute of Oncology Ljubljana, adult B-cell lymphoma patients treated with or previously exposed to rituximab received the Comirnaty® mRNA COVID-19 vaccine. Antibody responses to the SARS-CoV-2 spike and nucleoprotein were measured at baseline, 14 days after the second dose, and at 3, 6, 9, and 12 months. A third dose was administered at 6 months. T-cell responses (IFN-γ release) were assessed in patients before and after the primary series and booster dose. Lymphocyte subsets were analysed pre-vaccination. Adverse events and nutritional status were monitored.

Patients undergoing anti-CD20 therapy showed absent antibody responses. Longer intervals since rituximab correlated with peripheral B-cell repopulation. However, even after reaching normal B-cell counts, patients’ antibody responses after revaccination remained significantly lower than in controls.

Rituximab is associated with impaired vaccine-induced antibody responses. Despite recovery of peripheral B-cell counts, patients with B-cell lymphoma show reduced humoral responses compared with healthy individuals following booster COVID-19 vaccination.

## Linked entities

- **Proteins:** IFNG (interferon gamma)
- **Diseases:** B-cell lymphoma (MONDO:0015759), SARS-CoV-2 (MONDO:0100096)

## Full-text entities

- **Genes:** FCGR3A (Fc gamma receptor IIIa) [NCBI Gene 2214] {aka CD16-II, CD16A, FCG3, FCGR3, FCRIIIA, FcGRIIIA}, KRT20 (keratin 20) [NCBI Gene 54474] {aka CD20, CK-20, CK20, K20, KRT21}, N (nucleocapsid phosphoprotein) [NCBI Gene 43740575], IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, NCAM1 (neural cell adhesion molecule 1) [NCBI Gene 4684] {aka CD56, MSK39, NCAM}, CD69 (CD69 molecule) [NCBI Gene 969] {aka AIM, BL-AC/P26, CLEC2C, EA1, GP32/28, MLR-3}, APC (APC regulator of Wnt signaling pathway) [NCBI Gene 324] {aka BTPS2, DESMD, DP2, DP2.5, DP3, GS}, VTN (vitronectin) [NCBI Gene 7448] {aka V75, VN, VNT}, S (surface glycoprotein) [NCBI Gene 43740568] {aka spike glycoprotein}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CD19 (CD19 molecule) [NCBI Gene 930] {aka B4, CVID3}, PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788] {aka B220, CD45, CD45R, GP180, IMD105, L-CA}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}
- **Diseases:** lymphoma (MESH:D008223), B-cell lymphoma (MESH:D016393), COVID-19 (MESH:D000086382), immunodeficiency (MESH:D007153), autoimmune diseases (MESH:D001327), infected (MESH:D007239), HIV infection (MESH:D015658), Cancer (MESH:D009369), Malnutrition (MESH:D044342), follicular or mantle cell lymphoma (MESH:D020522)
- **Chemicals:** S (MESH:D013455), N (MESH:D009584), EDTA (MESH:D004492), Rituximab (MESH:D000069283), CHOP (-)
- **Species:** Homo sapiens (human, species) [taxon 9606], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13012384/full.md

## References

31 references — full list in the complete paper: https://tomesphere.com/paper/PMC13012384/full.md

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Source: https://tomesphere.com/paper/PMC13012384