The impact of B‐cell‐directed therapy on SARS‐CoV‐2 vaccine efficacy in chronic lymphocytic leukaemia

Abstract

Prior reports evaluating SARS‐CoV‐2 vaccine efficacy in chronic lymphocytic leukaemia (CLL) used semiquantitative measurements of anti‐S to evaluate immunity; however, neutralization assays were used to assess functional immunity in the trials leading to vaccine approval. Here, we identified decreased rates of seroconversion in vaccinated CLL patients and lower anti‐S levels compared to healthy controls. Notably, we demonstrated similar results with the Roche anti‐S assay and neutralization activity. Durable responses were seen at six months; augmentation with boosters was possible in responding patients. Absence of normal B cells, frequently seen in patients receiving Bruton tyrosine kinase and B‐cell lymphoma 2 inhibitors, was a strong predictor of lack of seroconversion.

Hybrid immunity in immunocompromised patients with CLL after SARS-CoV-2 infection followed by booster mRNA vaccination

“…The variation in time between COVID-19 and the start of vaccination and between vaccinations may affect the magnitude of the immune responses. Neutralizing antibodies were not measured even though we found a strong correlation between serum and saliva IgG levels with neutralization in the same patients earlier 2 and confirmed by others 18 . Finally, there was no control group tested in parallel with this real-world cohort and the groups studied (healthy donors and CLL) were not COVID-19 convalescents and received only two vaccine doses at the time of reporting 5,7,10,12 .…”

SARS‐CoV‐2 humoral responses following booster BNT162b2 vaccination in patients with B‐cell malignancies

“… 20 , 21 , 22 Other studies have however failed to demonstrate enhanced humoral immune responses in patients with B‐cell malignancies who are seronegative after the second dose. 7 , 23 , 24 …”

“…Patients with hematological malignancies are not only at increased risk of severe COVID19 disease and worse outcomes 2,3 but also at increased risk of serological non‐response to vaccination 4 . Recent data in patients with chronic lymphocytic leukemia (CLL), Non‐Hodgkin's lymphoma (NHL), and Waldenström macroglobulinemia (WM) CLL, NHL, and WM patients report less effective humoral responses following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), as reflected by low titers of neutralizing antibodies (NAbs) 5,6 Being on active treatment, particularly with anti‐CD20 monoclonal antibodies, Bruton's Tyrosine Kinase inhibitors and B‐cell lymphoma 2 inhibitors, has emerged as the main negative prognostic factor for suboptimal antibody response in these 5–7 …”

“…4 Recent data in patients with chronic lymphocytic leukemia (CLL), Non-Hodgkin's lymphoma (NHL), and Waldenström macroglobulinemia (WM) CLL, NHL, and WM patients report less effective humoral responses following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as reflected by low titers of neutralizing antibodies (NAbs) 5,6 Being on active treatment, particularly with anti-CD20 monoclonal antibodies, Bruton's Tyrosine Kinase inhibitors and B-cell lymphoma 2 inhibitors, has emerged as the main negative prognostic factor for suboptimal antibody response in these. [5][6][7] Vaccination has lowered the risk of severe COVID-19 disease significantly among immunocompetent, and immunocompromised individuals, despite suboptimal humoral responses among the latter. 4 The emergence of new SARS-CoV-2 variants and the declining humoral immunity over time 8 have necessitated the administration of booster vaccine doses.…”

Patients with Chronic Lymphocytic Leukemia Have a Very High Risk of Ineffective Response to the BNT162b2 Vaccine

“…Although in our analysis we did not find any significant statistical correlation between disease stage, number of previous therapies, and humoral immune response (bias due to small sample size), we can assume that both conditions adversely impact the immunological response to the vaccine, as reported in literature [ 18 , 20 ].…”