Humoral and cellular responses after COVID-19 booster vaccination in patients recently treated with anti-CD20 antibodies

Nishikubo, Masashi; Shimomura, Yoshimitsu; Yamamoto, Ryusuke; Yoshioka, Satoshi; Maruoka, Hayato; Nasu, Seiko; Nishioka, Tomomi; Sakizono, Kenji; Mitsuyuki, Satoshi; Kubo, Tomoyo; Okada, Naoki; Nakagawa, Daishi; Kamijo, Kimimori; Imoto, Hiroharu; Nagai, Yuya; Hiramoto, Nobuhiro; Yonetani, Noboru; Kondo, Tadakazu; Miyakoshi, Chisato; Doi, Asako; Ishikawa, Takayuki

doi:10.1038/s41408-023-00792-z

Cited by 5 publications

(4 citation statements)

References 13 publications

(24 reference statements)

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“…Despite recent evidence showing a modest increase in humoral response to a third vaccine dose, 25 we did not find that SARS‐CoV‐2 vaccination status or number of vaccine doses to be related to clinical outcomes. Furthermore, in line with previous studies, 10 we found that T‐C monoclonal antibody prophylaxis was associated with a lower risk of severe COVID‐19, suggesting an essential role for this intervention in protecting patients receiving anti‐CD20 therapy.…”

Section: Discussioncontrasting

confidence: 99%

An international multicenter study comparing COVID‐19 omicron outcomes in patients with hematological malignancies treated with obinutuzumab versus rituximab

Shafat,

Grupel,

Porges

et al. 2024

Cancer Medicine

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ObjectivesHematological malignancy (HM) patients treated with anti‐CD20 monoclonal antibodies are at higher risk for severe COVID‐19. A previous single‐center study showed worse outcomes in patients treated with obinutuzumab compared to rituximab. We examined this hypothesis in a large international multicenter cohort.MethodsWe included HM patients from 15 centers, from five countries treated with anti‐CD20, comparing those treated with obinutuzumab (O‐G) to rituximab (R‐G) between December 2021 and June 2022, when Omicron lineage was dominant.ResultsWe collected data on 1048 patients. Within the R‐G (n = 762, 73%), 191 (25%) contracted COVID‐19 compared to 103 (36%) in the O‐G. COVID‐19 patients in the O‐G were younger (61 ± 11.7 vs. 64 ± 14.5, p = 0.039), had more indolent HM diagnosis (aggressive lymphoma: 3.9% vs. 67.0%, p < 0.001), and most were on maintenance therapy at COVID‐19 diagnosis (63.0% vs. 16.8%, p < 0.001). Severe‐critical COVID‐19 occurred in 31.1% of patients in the O‐G and 22.5% in the R‐G. In multivariable analysis, O‐G had a 2.08‐fold increased risk for severe‐critical COVID‐19 compared to R‐G (95% CI 1.13–3.84), adjusted for Charlson comorbidity index, sex, and tixagevimab/cilgavimab (T‐C) prophylaxis. Further analysis comparing O‐G to R‐G demonstrated increased hospitalizations (51.5% vs. 35.6% p = 0.008), ICU admissions (12.6% vs. 5.8%, p = 0.042), but the nonsignificant difference in COVID‐19‐related mortality (n = 10, 9.7% vs. n = 12, 6.3%, p = 0.293).ConclusionsDespite younger age and a more indolent HM diagnosis, patients receiving obinutuzumab had more severe COVID‐19 outcomes than those receiving rituximab. Our findings underscore the need to evaluate the risk–benefit balance when considering obinutuzumab therapy for HM patients during respiratory viral outbreaks.

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Section: Discussioncontrasting

confidence: 99%

An international multicenter study comparing COVID‐19 omicron outcomes in patients with hematological malignancies treated with obinutuzumab versus rituximab

Shafat,

Grupel,

Porges

et al. 2024

Cancer Medicine

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“…However, they also revealed that T cell responses to COVID-19 were observed even in cases that did not seroconvert. A previous study conducted by Nishikubo et al ( 22 ) revealed that the third vaccine booster can produce a T cell response to COVID-19 regardless of the interval of anti-CD20 antibody treatment, and that regardless of the antibody titer, it was revealed that prevention of COVID-19 can be achieved. In conclusion, for the acquisition of antibodies by vaccination of B-cell lymphomas during or after treatment with anti-CD20 antibodies, a certain amount of CD19 and CD4 is considered necessary (in the present study, CD19 at 100/µl or higher and CD4 at 400/µl or higher, preferably both).…”

Section: Discussionmentioning

confidence: 97%

COVID‑19 antibody production by vaccination in chemotherapy with CD20 antibody for B‑cell lymphoma

Tsutsumi,

Ito,

Horikita

et al. 2023

Mol Clin Oncol

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Most hematologic diseases are immunosuppressed, either by the disease itself or by treatment. As such, the implementation of vaccination is largely at the discretion of the attending physician. In this context, an objective measure is needed, therefore the index of vaccination against coronavirus disease 2019 (COVID-19) in B-cell lymphomas treated with antibody therapy against CD20 (including after the completion of therapy) was examined. A total of 40 patients with B-cell lymphoma during or after antibody therapy against CD20 were vaccinated twice with the BNT162b2 messenger RNA (mRNA) COVID-19 vaccine (Pfizer, Inc. and BioNTech SE.) at 3-week intervals and then again six months later with the same vaccine or mRNA-1273 (Moderna, Inc.). Antibody testing was conducted ~1 month after the third vaccination. Analysis was performed using the antibody titers to the anti-spike immunoglobulin assay, with a titer of 0.8 U/ml or higher (considered positive) and a titer of 264 U/ml or higher (considered the value at which the efficacy of the vaccine can be fully expected). Significant factors of antibody acquisition were identified when i) antibody titers were 0.8 U/ml or higher (CD4 ≥400/µl), ii) no anti-CD20 antibody maintenance therapy was undertaken (CD19 ≥100/µl), iii) patients were not on treatment (CD4 ≥400/µl), or 4) at least six months had passed since treatment ended (CD19 ≥100/µl). When antibody titers were 264 U/ml or higher, the treatment method, the stage of the primary disease and other factors related to the condition treatment method of the patient were relevant. When these were analyzed by multivariate analysis, the significant factor when antibody titers were set to 0.8 U/ml was CD19 ≥100/µl. In contrast, when setting them to 264 U/ml or higher, CD4 ≥400/µl was not significant, but there was a tendency for it to be related. The findings of the present study on vaccine-induced antibody acquisition in patients with B-cell lymphoma indicated that it is desirable to have a CD19 titer of at least 100/µl and a CD4 titer of at least 400/µl (both conditions should be met), and that no maintenance therapy with anti-CD20 antibody should be administered for at least six months after the last treatment or completion of the treatment. Interestingly, when the criteria for antibody titers were compared between 0.8 U/ml, where antibody titer is detected, and 264 U/ml, where vaccine efficacy is expected, several key factors were different. It is possible that these key factors may change depending on the antibody titer used as a criterion.

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“…There was a decreased incidence of COVID-19 hospitalization among MS patients who had COVID-19 vaccinations more than six months after the last rituximab infusion [ 56 ]. Additionally, In a study conducted by Nishikubo et al on hematological patients, it was suggested that patients who had recently received anti-CD20 could benefit from a third booster dose of the COVID-19 vaccine [ 59 ]. Therefore, although patients receiving immunosuppressors might benefit from COVID-19 vaccination, determining the optimal timing for administering the COVID-19 vaccine in these patients should be carefully evaluated.…”

Section: Discussionmentioning

confidence: 99%

Effects of vaccination on COVID-19 infection symptoms in multiple sclerosis patients

Sharifi,

Rezaeimanesh,

Moradi

et al. 2024

eNeurologicalSci

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Humoral and cellular responses after COVID-19 booster vaccination in patients recently treated with anti-CD20 antibodies

Cited by 5 publications

References 13 publications

An international multicenter study comparing COVID‐19 omicron outcomes in patients with hematological malignancies treated with obinutuzumab versus rituximab

An international multicenter study comparing COVID‐19 omicron outcomes in patients with hematological malignancies treated with obinutuzumab versus rituximab

COVID‑19 antibody production by vaccination in chemotherapy with CD20 antibody for B‑cell lymphoma

Effects of vaccination on COVID-19 infection symptoms in multiple sclerosis patients

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