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

Abstract

Patients with chronic lymphocytic leukemia (CLL) have an impaired antibody response to 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 two-dose vaccination regimen. Anti-SARS-CoV-2S and neutralizing 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 to treatment-naïve patients (40.0%, n=16/40; OR=4.9, 95% CI 1.9-12.9; p<0.001) and patients off-therapy (40.6%, n=13/32; OR=5.0, 95% CI 1.8-14.1; p<0.001), (p<0.001). In those actively treated with 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 one of the 28 patients (3.6%) treated with anti-CD20 antibodies <12 months prior to vaccination responded. The anti-SARS-CoV-2S antibody levels correlated linearly with neutralizing antibody titers (r=0.732, p<0.001). 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<0.001) and serum IgA levels ≥80 mg/dL (OR=5.8, 95% CI 2.1-15.9; p<0.001) In conclusion, in patients with CLL/SLL who failed to achieve a humoral response after standard two-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.

Antibody responses following third mRNA COVID-19 vaccination in patients with cancer and potential timing of a fourth vaccination

“…The group of patients with hematologic cancers receiving active cancer therapies during the second and third mRNA vaccinations exhibited significantly lower seroconversion following the third vaccination compared to those who did not receive therapies ( Table S1 C; Figure S1 D), in agreement with Herishanu et al. (2022) .…”

“…Patients with cancer are at risk of severe COVID-19 disease due to immunosuppression caused by cancer and/or cancer therapies ( Ehmsen et al., 2021b ; Tian et al., 2020 ). We and others have characterized the anti-SARS-CoV-2 immune response after two doses of COVID-19 mRNA vaccines in patients with solid and hematologic cancers and observed insufficient responses in a substantial portion ( Ehmsen et al., 2021a ; Gounant et al., 2022 ; Herishanu et al., 2022 ). We further showed that the anti-SARS-CoV-2 spike receptor binding domain (anti-S) IgG antibody titers declined rapidly within the first 3 months after the second vaccination, indicating the need to boost the immune response with a third vaccination.…”

Omicron-Specific Cytotoxic T-Cell Responses After a Third Dose of mRNA COVID-19 Vaccine Among Patients With Multiple Sclerosis Treated With Ocrelizumab

“…In anti-CD20-treated patients with MS, SARS-CoV-2-specific antibody titers are low or undetectable after 2 doses of mRNA vaccine [5][6][7] and are not restored after a third dose, as shown here and for patients with lymphoma. 5,8 Antibodies are crucial in the prevention of infection through inhibition of viral entry and in the elimination of infected cells through antibody-mediated killing. Even if antibody responses are largely impaired in anti-CD20-treated patients, T-cell responses after 2 vaccine doses developed similarly to immunocompetent individuals.…”

Multiple Sclerosis Patients and Disease Modifying Therapies: Impact on Immune Responses against COVID-19 and SARS-CoV-2 Vaccination

“…Accordingly, administration of the third dose vaccination in MS patients, transplant recipients and patients with cancer increased the levels of humoral responses, even in patients who were sero-negative after the second dose due to anti-CD20 therapies. Therefore, these findings indicate the enhancer effect of additional COVID-19 vaccine dose on antibody levels in immunosuppressed group of patients [74][75][76][77][78][79][80][81]. Glatiramer acetate does not deplete lymphocytes; hence, it is unlikely to affect the protective immune responses to these vaccines in MS patients.…”