tetano
Editor, Senior Moderator
J Hematol
. 2023 Aug;12(4):170-175.
doi: 10.14740/jh1140. Epub 2023 Aug 8. Local and Systemic Immunity During Five Vaccinations Against SARS-CoV-2 in Zanubrutinib-Treated Patients With Chronic Lymphocytic Leukemia
Maria Andersson[SUP] 1 2 3 [/SUP], Jinghua Wu[SUP] 4 3 [/SUP], David Wullimann[SUP] 4 [/SUP], Yu Gao[SUP] 4 [/SUP], Mikael Aberg[SUP] 5 [/SUP], Sandra Muschiol[SUP] 6 7 [/SUP], Katie Healy[SUP] 6 [/SUP], Sabrina Naud[SUP] 8 [/SUP], Gordana Bogdanovic[SUP] 6 7 [/SUP], Marzia Palma[SUP] 1 2 [/SUP], Hakan Mellstedt[SUP] 1 [/SUP], Puran Chen[SUP] 4 [/SUP], Hans-Gustaf Ljunggren[SUP] 4 [/SUP], Lotta Hansson[SUP] 1 2 [/SUP], Margaret Sallberg Chen[SUP] 8 [/SUP], Marcus Buggert[SUP] 4 [/SUP], Hanna M Ingelman-Sundberg[SUP] 1 9 3 [/SUP], Anders Osterborg[SUP] 1 2 3 [/SUP]
Affiliations
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.
Keywords: CLL; Immunity; SARS-CoV-2; Vaccination; Zanubrutinib.
. 2023 Aug;12(4):170-175.
doi: 10.14740/jh1140. Epub 2023 Aug 8. Local and Systemic Immunity During Five Vaccinations Against SARS-CoV-2 in Zanubrutinib-Treated Patients With Chronic Lymphocytic Leukemia
Maria Andersson[SUP] 1 2 3 [/SUP], Jinghua Wu[SUP] 4 3 [/SUP], David Wullimann[SUP] 4 [/SUP], Yu Gao[SUP] 4 [/SUP], Mikael Aberg[SUP] 5 [/SUP], Sandra Muschiol[SUP] 6 7 [/SUP], Katie Healy[SUP] 6 [/SUP], Sabrina Naud[SUP] 8 [/SUP], Gordana Bogdanovic[SUP] 6 7 [/SUP], Marzia Palma[SUP] 1 2 [/SUP], Hakan Mellstedt[SUP] 1 [/SUP], Puran Chen[SUP] 4 [/SUP], Hans-Gustaf Ljunggren[SUP] 4 [/SUP], Lotta Hansson[SUP] 1 2 [/SUP], Margaret Sallberg Chen[SUP] 8 [/SUP], Marcus Buggert[SUP] 4 [/SUP], Hanna M Ingelman-Sundberg[SUP] 1 9 3 [/SUP], Anders Osterborg[SUP] 1 2 3 [/SUP]
Affiliations
- PMID: 37692865
- PMCID: PMC10482612
- DOI: 10.14740/jh1140
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.
Keywords: CLL; Immunity; SARS-CoV-2; Vaccination; Zanubrutinib.