Humoral and cellular responses after COVID-19 vaccination in anti-CD20-treated lymphoma patients

Liebers, Nora; Speer, Claudius; Benning, Louise; Bruch, Peter‐Martin; Krämer, Isabelle; Meißner, Julia; Schnitzler, Paul; Kräusslich, Hans‐Georg; Dreger, Peter; Müller‐Tidow, Carsten; Poschke, Isabel; Dietrich, Sascha

doi:10.1182/blood.2021013445

Cited by 72 publications

(96 citation statements)

References 15 publications

(10 reference statements)

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“…Regarding CLL patients on therapy, 74.4% (OR 5.20, p < 0.001) treated within the last 12 months, and 78% currently on therapy failed vaccination. We found markedly impaired vaccine response with all forms of therapy including 18/21 on ibrutinib, 30 7/9 on CD20 antibody, 31 3/4 on FCR and 3/4 on venetoclax.…”

Section: Discussionmentioning

confidence: 76%

COVID‐19 vaccine failure in chronic lymphocytic leukaemia and monoclonal B‐lymphocytosis; humoural and cellular immunity

Shen

Freeman

Holland³

et al. 2022

Br J Haematol

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Summary Chronic lymphocytic leukaemia (CLL) is associated with immunocompromise and high risk of severe COVID‐19 disease and mortality. Monoclonal B‐cell lymphocytosis (MBL) patients also have immune impairment. We evaluated humoural and cellular immune responses in 181 patients with CLL (160) and MBL (21) to correlate failed seroconversion [<50 AU/ml SARS‐CoV‐2 II IgG assay, antibody to spike protein; Abbott Diagnostics)] following each of two vaccine doses with clinical and laboratory parameters. Following first and second doses, 79.2% then 45% of CLL, and 50% then 9.5% of MBL patients respectively remained seronegative. There was significant association between post dose two antibody level with pre‐vaccination reduced IgM (p < 0.0001), IgG2 (p < 0.035), and IgG3 (p < 0.046), and CLL therapy within 12 months (p < 0.001) in univariate analysis. By multivariate analysis, reduced IgM (p < 0.0002) and active therapy (p < 0.0002) retained significance. Anti‐spike protein levels varied widely and were lower in CLL than MBL patients, and both lower than in normal donors. Neutralisation activity showed anti‐spike levels <1000 AU/ml were usually negative for both an early viral clade and the contemporary Delta variant and 72.9% of CLL and 53.3% of MBL failed to reach levels ≥1000 AU/ml. In a representative sample, ~80% had normal T‐cell responses. Failed seroconversion occurred in 36.6% of treatment‐naïve patients, in 78.1% on therapy, and in 85.7% on ibrutinib.

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Section: Discussionmentioning

confidence: 76%

COVID‐19 vaccine failure in chronic lymphocytic leukaemia and monoclonal B‐lymphocytosis; humoural and cellular immunity

Shen

Freeman

Holland³

et al. 2022

Br J Haematol

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“…co-morbidities, medications, germline polymorphisms and more specific immune profiling) were not measured in this study and likely influence anti-COVID-19 immunity. We acknowledge that the specific T-cell response to the vaccine was not measured in this study, but likely plays a role in the development of COVID-19 immunity [26] . Our data confirms the importance of appropriate counselling in these high-risk lymphoma patients that are vaccinated, but not adequately protected against SARS-CoV-2 infection.…”

Section: Discussionmentioning

confidence: 99%

B-cell cytopenia and time to last B-cell-depleting therapy predict response to SARS-COV-2 vaccines in patients with lymphoproliferative disorders

Tanguay

Boutin

Laumaea

et al. 2022

Vaccine

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Patients with B-non-Hodgkin lymphoma (NHL) are at increased risk of morbidity and mortality from SARS-CoV-2. We investigated the relationship between B cell cytopenia and the SARS-CoV-2 vaccine response in B-NHL patients. We measured anti-RBD antibodies and the lymphocyte immunophenotype in 19 controls, 22 lymphoma patients on observation (cohort 1) and 55 lymphoma patients receiving their vaccines post B-cell depleting therapy (cohort 2). Half of the lymphoma patients in both cohorts achieved seropositivity compared to 100% of controls. In cohort 2, only 5% achieved an antibody response in the first year post B-cell depleting treatment, vs 88% treated >2 years prior. Also, 28% of patients with <50 B cells/µl achieved a serologic response vs 86% of patients with B-cell >50 B cells/µl. B-cell cytopenia is profound within the first year of exposure to B-cell depleting treatment, therefore an additional dose of vaccine within that timeframe is unlikely to raise antibody levels.

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“…These suppressive effects are most evident for all B cell-depleting treatments (including CD20, BCMA and CD38 targeted therapies; Box 2 ). The magnitude of a patient’s spike protein-reactive IgG response correlates with the absolute number of B cells 131 and the suppressive effects of B cell-depleting therapies probably last for ≥1 year after treatment cessation 120 , 132 , putting these patients at an increased risk of breakthrough infections.…”

Section: Vaccination In Patients With Cancermentioning

confidence: 99%

“…for ≥1 year after treatment cessation 120,132 , putting these patients at an increased risk of breakthrough infections.…”

Section: Box 2 | Risks Of Reduced Antibody Responses After Covid-19 V...mentioning

confidence: 99%

COVID-19 vaccines in patients with cancer: immunogenicity, efficacy and safety

et al. 2022

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Patients with cancer have a higher risk of severe coronavirus disease (COVID-19) and associated mortality than the general population. Owing to this increased risk, patients with cancer have been prioritized for COVID-19 vaccination globally, for both primary and booster vaccinations. However, given that these patients were not included in the pivotal clinical trials, considerable uncertainty remains regarding vaccine efficacy, and the extent of humoral and cellular immune responses in these patients, as well as the risks of vaccine-related adverse events. In this Review, we summarize the current knowledge generated in studies conducted since COVID-19 vaccines first became available. We also highlight critical points that might affect vaccine efficacy in patients with cancer in the future.

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Humoral and cellular responses after COVID-19 vaccination in anti-CD20-treated lymphoma patients

Cited by 72 publications

References 15 publications

COVID‐19 vaccine failure in chronic lymphocytic leukaemia and monoclonal B‐lymphocytosis; humoural and cellular immunity

COVID‐19 vaccine failure in chronic lymphocytic leukaemia and monoclonal B‐lymphocytosis; humoural and cellular immunity

B-cell cytopenia and time to last B-cell-depleting therapy predict response to SARS-COV-2 vaccines in patients with lymphoproliferative disorders

COVID-19 vaccines in patients with cancer: immunogenicity, efficacy and safety

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