Anti-SARS-CoV-2 cellular response after 2 and 3 doses of BNT162b2 mRNA vaccine in lymphoma patients receiving anti-CD20 antibodies

Gressens, Simon B.; Wiedemann, Aurélie; Déchenaud, Marie; Dupuis, Jehan; Gallien, Sébastien; Melica, Giovanna; Haouin, Corinne; Lemonnier, François; Lévy, Yves

doi:10.1016/j.vaccine.2023.01.064

Cited by 3 publications

(3 citation statements)

References 18 publications

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“…Also in the three-dose zanubrutinib vaccine report by Nguyen et al, T-cell reactivities were increased by a third dose [ 13 ]. A third-dose boost was also reported in other subsets of patients with CLL [ 19 , 20 ], whereas in lymphoma patients, a Th1, but not CD8 + T cell response, was reported by dose 3 [ 21 ].…”

Section: Discussionmentioning

confidence: 91%

Local and Systemic Immunity During Five Vaccinations Against SARS-CoV-2 in Zanubrutinib-Treated Patients With Chronic Lymphocytic Leukemia

Andersson,

Wu,

Wullimann

et al. 2023

J Hematol

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Background Patients with chronic lymphocytic leukemia (CLL) are vulnerable to coronavirus disease 2019 (COVID-19) and are at risk of inferior response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, especially if treated with the first-generation Bruton’s tyrosine kinase inhibitor (BTKi) ibrutinib. We aimed to evaluate the impact of the third-generation BTKi, zanubrutinib, on systemic and mucosal response to SARS-CoV-2 vaccination. Methods Nine patients with CLL with ongoing zanubrutinib therapy were included and donated blood and saliva during SARS-CoV-2 vaccination, before vaccine doses 3 and 5 and 2 - 3 weeks after doses 3, 4, and 5. Ibrutinib-treated control patients (n = 7) and healthy aged-matched controls (n = 7) gave blood 2 - 3 weeks after vaccine dose 5. We quantified reactivity and neutralization capacity of SARS-CoV-2-specific IgG and IgA antibodies (Abs) in both serum and saliva, and reactivity of T cells activated with viral peptides. Results Both zanubrutinib- and ibrutinib-treated patients had significantly, up to 1,000-fold, lower total spike-specific Ab levels after dose 5 compared to healthy controls (P < 0.01). Spike-IgG levels in serum from zanubrutinib-treated patients correlated well to neutralization capacity (r = 0.68; P < 0.0001) and were thus functional. Mucosal immunity (specific IgA in serum and saliva) was practically absent in zanubrutinib-treated patients even after five vaccine doses, whereas healthy controls had significantly higher levels (tested in serum after vaccine dose 5) (P < 0.05). In contrast, T-cell reactivity against SARS-CoV-2 peptides was equally high in zanubrutinib- and ibrutinib-treated patients as in healthy control donors. Conclusions In our small cohort of zanubrutinib-treated CLL patients, we conclude that up to five doses of SARS-CoV-2 vaccination induced no detectable IgA mucosal immunity, which likely will impair the primary barrier defence against the infection. Systemic IgG responses were also impaired, whereas T-cell responses were normal. Further and larger studies are needed to evaluate the impact of these findings on disease protection.

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Section: Discussionmentioning

confidence: 91%

Local and Systemic Immunity During Five Vaccinations Against SARS-CoV-2 in Zanubrutinib-Treated Patients With Chronic Lymphocytic Leukemia

Andersson,

Wu,

Wullimann

et al. 2023

J Hematol

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“…Indeed, observational studies evidenced detectable SARS‐CoV‐2‐specific T‐cell responses in a substantial proportion of vaccinated B‐NHL patients independently from humoral response status (Table 3). 15,16 In a study by Gressens et al., primary vaccination induced specific CD4 and CD8 T‐cell responses in 14 lymphoma patients treated with anti‐CD20 plus chemotherapy; of note, only one of them developed humoral response 53 …”

Section: Covid‐19 Vaccinationmentioning

confidence: 99%

Management of vaccinations in patients with non‐Hodgkin lymphoma

Merli,

Costantini,

Tafuri

et al. 2024

Br J Haematol

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SummaryVaccinations are fundamental tools in preventing infectious diseases, especially in immunocompromised patients like those affected by non‐Hodgkin lymphomas (NHLs). The COVID‐19 pandemic made clinicians increasingly aware of the importance of vaccinations in preventing potential life‐threatening SARS‐CoV‐2‐related complications in NHL patients. However, several studies have confirmed a significant reduction in vaccine‐induced immune responses after anti‐CD20 monoclonal antibody treatment, thus underscoring the need for refined immunization strategies in NHL patients. In this review, we summarize the existing data about COVID‐19 and other vaccine's efficacy in patients with NHL and propose multidisciplinary team‐based recommendations for the management of vaccines in this specific group of patients.

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“…Conversely, in MM patents, T cell responses are weaker and more heterogeneous than healthy controls. [ 270 , 271 ] 3 doses of mRNA vaccine SARS-CoV-2 variants expect Omicron CLL • Robust hybrid immunity in serum, saliva, and T-cell compartments in patients [ 272 ] mRNA-1273 Omicron MM • MM patients who received mRNA-1273 vaccination developed severe infections 10 weeks after vaccination, despite the production of protective antibodies • After administration of two mRNA vaccines to people with NSCLC and healthy participants, it was observed that NSCLC patients showed less neutralizing activity against live viruses compared to their healthy counterparts [ 273 ] Moderna (second vaccine) Pfizer (second vaccine) Janssen (1 vaccine) Omicron AML • Boosted immunity [ 274 ] Monoclonal antibodies Anti-CD38 therapy Alpha and delta MM • It is approved in the first line in combination with other agents (immunomodulatory drugs—IMID or PI) and high-dose steroids • Anti-CD38 therapy was even less associated with NAbs response among MM patients • Anti-CD38 antibodies also cause a relative depletion of NK cells, which could contribute to immunodeficiency in MM receiving these immunosuppressive regimens [ 275 ] Anti-CD20 SARS-CoV-2 (delta) B-cell malignancies • Disrupts humoral responses after two or three vaccinations • Patients who received anti-CD20 antibodies showed limited efficacy of a BNT162b2 booster dose [ 276 – 279 ] Anti-BCMA MAbs Omicron, WA1, and delta MM • After the third time, no significant increase in anti-spike Ab levels was observed in patients treated with anti-BCMA MAbs [ 280 ] …”

Section: Haematological Malignancies and Covid-19mentioning

confidence: 99%

COVID-19 in patients with anemia and haematological malignancies: risk factors, clinical guidelines, and emerging therapeutic approaches

Kakavandi,

Hajikhani,

Azizi

et al. 2024

Cell Commun Signal

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Extensive research in countries with high sociodemographic indices (SDIs) to date has shown that coronavirus disease 2019 (COVID-19) may be directly associated with more severe outcomes among patients living with haematological disorders and malignancies (HDMs). Because individuals with moderate to severe immunodeficiency are likely to undergo persistent infections, shed virus particles for prolonged periods, and lack an inflammatory or abortive phase, this represents an overall risk of morbidity and mortality from COVID-19. In cases suffering from HDMs, further investigation is needed to achieve a better understanding of triviruses and a group of related variants in patients with anemia and HDMs, as well as their treatment through vaccines, drugs, and other methods. Against this background, the present study aimed to delineate the relationship between HDMs and the novel COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Besides, effective treatment options for HDM cases were further explored to address this epidemic and its variants. Therefore, learning about how COVID-19 manifests in these patients, along with exploiting the most appropriate treatments, may lead to the development of treatment and care strategies by clinicians and researchers to help patients recover faster.

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Anti-SARS-CoV-2 cellular response after 2 and 3 doses of BNT162b2 mRNA vaccine in lymphoma patients receiving anti-CD20 antibodies

Cited by 3 publications

References 18 publications

Local and Systemic Immunity During Five Vaccinations Against SARS-CoV-2 in Zanubrutinib-Treated Patients With Chronic Lymphocytic Leukemia

Local and Systemic Immunity During Five Vaccinations Against SARS-CoV-2 in Zanubrutinib-Treated Patients With Chronic Lymphocytic Leukemia

Management of vaccinations in patients with non‐Hodgkin lymphoma

COVID-19 in patients with anemia and haematological malignancies: risk factors, clinical guidelines, and emerging therapeutic approaches

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