Efficacy of a third BNT162b2 mRNA COVID-19 vaccine dose in patients with CLL who failed standard 2-dose vaccination

Yair Herishanu, Galia Rahav, Shai Levi, Andrei Braester, Gilad Itchaki, Osnat Bairey, Najib Dally, Lev Shvidel, Tomer Ziv-Baran, Aaron Polliack, Tamar Tadmor, Ohad Benjamini, Israeli CLL Study Group, Yair Herishanu, Galia Rahav, Shai Levi, Andrei Braester, Gilad Itchaki, Osnat Bairey, Najib Dally, Lev Shvidel, Tomer Ziv-Baran, Aaron Polliack, Tamar Tadmor, Ohad Benjamini, Israeli CLL Study Group

Abstract

Patients with chronic lymphocytic leukemia (CLL) have an impaired antibody response to coronavirus disease 2019 (COVID-19) vaccination. Here, we evaluated the antibody response to a third BNT162b2 mRNA vaccine in patients with CLL/small lymphocytic lymphoma (SLL) who failed to achieve a humoral response after standard 2-dose vaccination regimen. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies were measured 3 weeks after administration of the third dose. In 172 patients with CLL, the antibody response rate was 23.8%. Response rate among actively treated patients (12.0%; n = 12/100) was lower compared with treatment-naïve patients (40.0%; n = 16/40; OR = 4.9, 95% CI 1.9-12.9; P < .001) and patients off-therapy (40.6%; n = 13/32; OR = 5.0, 95% CI 1.8-14.1; P < .001), (P < .001). In patients actively treated with Bruton's tyrosine kinase (BTK) inhibitors or venetoclax ± anti-CD20 antibody, response rates were extremely low (15.3%, n = 9/59, and 7.7%, n = 3/39, respectively). Only 1 of the 28 patients (3.6%) treated with anti-CD20 antibodies <12 months prior to vaccination responded. In a multivariate analysis, the independent variables that were associated with response included lack of active therapy (OR = 5.6, 95% CI 2.3-13.8; P < .001) and serum immunoglobulin A levels ≥80 mg/dL (OR = 5.8, 95% CI 2.1-15.9; P < .001). In patients with CLL/SLL who failed to achieve a humoral response after standard 2-dose BNT162b2 mRNA vaccination regimen, close to a quarter responded to the third dose of vaccine. The antibody response rates were lower during active treatment and in patients with a recent exposure (<12 months prior to vaccination) to anti-CD20 therapy. This trial was registered at www.clinicaltrials.gov as #NCT04862806.

© 2022 by The American Society of Hematology.

Figures

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
Antibody response rate and titers after a third vaccine dose in patients with CLL who failed to respond after the standard 2-dose BNT162b2 mRNA vaccination regimen. (A-B) Antibody response rate (%) and anti–SARS-CoV-2 antibody levels in patients with CLL shown for the entire cohort and according to the disease status: all CLL patients (n = 172); treatment naïve (n = 40); on-therapy (n = 100); and off-therapy (n = 32). (C) Response rate in patients with CLL treated with Bruton's tyrosine kinase inhibitor (BTKi; n = 59) and venetoclax (Ven) ± anti-CD20 antibody (n = 39). (D) Correlation between serological titers and neutralizing antibody levels following log transformation (n = 24), (Pearson's correlation coefficient r = 0.732; P < .001; r2 = 0.536). In an additional 30 patients, the anti–SARS-CoV-2 and neutralizing antibodies levels were negative and therefore were invalid for analysis.
Figure 2.
Figure 2.
Adverse events reported after the third BNT162b2 vaccine dose in patients with CLL (n = 168).

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