Safety and immunogenicity of the BNT162b2 mRNA Covid-19 vaccine in patients with chronic lymphocytic leukemia: a prospective study

Abstract

Introduction: Immunization of patients with chronic lymphocytic leukemia (CLL) with vaccines against several infectious diseases has proven insufficient. Data on seroconversion of patients with CLL after vaccination against severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) are still young, but accumulating evidence shows low seroconversion rates. Methods: We conducted a prospective, noninterventional study evaluating the safety and immunogenicity of two doses of the BNT162b2 mRNA Covid-19 vaccine, administered 21 days apart in consecutive adult patients with CLL. Patients vaccinated with other vaccines against SARS-CoV-2, with a history of confirmed Coronavirus Disease 19 (COVID-19), with known human immunodeficiency virus infection, or with an inability to provide written informed consent were excluded. Sera were tested before the first and after the second dose of the vaccine for anti-SARS-CoV-2 receptor binding domain (RBD) spike protein IgG (anti-RBD), using the Abbott SARS-CoV-2 IgG II Quant assay (Abbott Laboratories, Abbott Park, IL, USA), with a cutoff value for seroconversion at 50 AU/ml. Results: Sixty-one patients (28 males/33 females) with CLL, with a median age of 61 years, were included in the study. The majority of the patients (82.0%) were lower (0–2) stage per the RAI staging system. The seroconversion rate at 14 days after the second dose was 45% and was correlated with RAI stage (0–2 versus 3–4; 51.0% versus 18.3%, p = 0.047), the treatment status (treatment naïve, previously treated, or actively treated patients; 63.0% versus 40.0% versus 26.1%, respectively, p = 0.031), the number of previous treatment lines (0–2 versus >2; 55.3% versus 8.3%, p = 0.004), and the platelet count of the patients (over or under 100 × 109/L; 52.9% versus 10.0%, p = 0.015). Moreover, there was a positive linear relationship between the antibody titers and the gamma-globulin levels ( r = 0.182, p = 0.046) and platelet count ( r = 0.277, p = 0.002). Finally, patients actively treated with venetoclax had higher antibody titers than those treated with ibrutinib (15.8 AU/ml versus 0.0 AU/ml, p = 0.047). No safety issues were identified while the emergence of adverse events was not correlated with immunogenicity. Discussion: This study confirms results from previous studies on the low seroconversion rates in patients with CLL vaccinated with the BNT162b2 mRNA Covid-19 vaccine and on the detrimental effect of advanced disease and multiple treatment lines on seroconversion, while it is suggested that treatment with venetoclax may offer a chance for higher antibody titers, suggesting a treatment strategy change during the pandemic provided that this result is confirmed by larger studies specifically designed to address this issue.

Immunogenicity of a third dose of the BNT162b2 COVID-19 vaccine in patients with CLL: effects on treatment selection

“…In an in-press study from our group, we showed that patients with CLL have suboptimal response to the BNT162b2 vaccine [11]. In the present study, we assessed the immunogenicity of a third dose of the BNT162b2 COVID-19 vaccine in patients with CLL.…”

“…This is an extension of a previous study on the immunogenicity and safety of two doses of the BNT162b2 mRNA COVID-19 vaccine in patients with CLL [11]. Adult patients with CLL from three tertiary hospitals in Athens, Greece, vaccinated against SARS-CoV-2 with three doses of the BNT162b2 mRNA COVID-19 vaccine participated in the present study after providing a written informed consent.…”

“…Sera were tested for anti-SARS-CoV-2 receptor-binding domain (RBD) spike protein IgG (anti-RBD), using the Abbott SARS-CoV-2 IgG II Quant assay (Abbott Laboratories, Abbott Park, IL, USA), a two-step chemiluminescent microparticle immunoassay for the qualitative/quantitative detection of IgG antibodies against the RBD of the S1 subunit of the spike protein in human serum and plasma on the Architect i system. The details of the method and its clinical sensitivity and specificity have been provided elsewhere [11,22,23]. The assay threshold of 50 AU/mL was set as the seroconversion cutoff in the present study.…”

“…Patients with chronic lymphocytic leukemia (CLL) are vulnerable to severe infection for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with high mortality rates [1][2][3][4][5]. Given the immune deregulation inherent to CLL but also aggravated by the treatment, response of patients with CLL to COVID-19 vaccines has been shown to be suboptimal [6][7][8][9][10][11]. Hence, strategies optimizing response to SARS-CoV-2 vaccination is crucial in these patients.…”

Comprehensive analysis of immune responses in CLL patients after heterologous COVID-19 vaccination

“…Circulating antibody levels were most closely correlated with treatment history. 9,37 After 2-dose vaccination, anti-spike (S) IgG was detected in 6/15 (40%) patients, including 2/6 (33%) off-therapy (#210, 212); 2/2 (100%) treatment-naïve (#211, 213); 1/4 (25%) on active venetoclax (#203); 0/3 (0%) on ibrutinib; 1/4 (25%) on anti-CD20 of less than 12 months (#209) (Figures. 2A and 3A; Supplementary Table 2).…”