Serological SARS-CoV-2 antibody response, potential predictive markers and safety of BNT162b2 mRNA COVID-19 vaccine in haematological and oncological patients

Abstract

Haemato-oncological patients are at risk in case of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Currently, vaccination is the best-evaluated preventive strategy. In the present study, we aimed to assess serological response, predictive markers, and safety of BNT162b2 in haemato-oncological patients. A total of 259 haemato-oncological patients were vaccinated with two 30 µg doses of BNT162b2 administered 21 days apart. Serological response was assessed by ELECSYS^® Anti-SARS-CoV-2-S immunoassay before vaccination, and at 3 and 7 weeks after the first dose (T1, T2). Safety assessment was performed. At T2 spike protein receptor binding domain (S/RBD) antibodies were detected in 71·4% of haematological and in 94·5% of oncological patients (P < 0·001). Haematological patients receiving systemic treatment had a 14·2-fold increased risk of non-responding (95% confidence interval 3·2-63·3, P = 0·001). Subgroups of patients with lymphoma or chronic lymphocytic leukaemia were at highest risk of serological non-response. Low immunoglobulin G (IgG) level, lymphocyte- and natural killer (NK)-cell counts were significantly associated with poor serological response (P < 0·05). Vaccination was well tolerated with only 2·7% of patients reporting severe side-effects. Patients with side-effects developed a higher S/RBD-antibody titre compared to patients without side-effects (P = 0·038). Haematological patients under treatment were at highest risk of serological non-response. Low lymphocytes, NK cells and IgG levels were found to be associated with serological non-response. Serological response in oncological patients was encouraging. The use of BNT162b2 is safe in haemato-oncological patients.

Keywords: BNT162b2 mRNA vaccine; COVID-19; chronic lymphocytic leukaemia; immune cells; serological response.

Fig 1

Patient flow in first and second vaccination campaign. The patient flowchart shows the two vaccination campaigns in our study. The number of patients at key target points such as date of vaccination and antibody determination are indicated. Time points and cause of dropouts are shown in the timeline.

Fig 2

Scatter plot of spike protein receptor binding domain (S/RBD)‐antibody titres at baseline (T0), after fist dose (T1) and after second dose (T2) divided by tumour entity. The absolute antibody titre in binding activity units per millilitre (BAU/ml) at the time of baseline‐, T1‐ and T2‐analysis is shown descriptively by the scatter plot. Each time‐point was divided into the tumour entities (haematological malignancy or solid tumour). The differences between antibody titres at each time‐point were tested and indicated with P values using analysis of variance (ANOVA).

Fig 3

Serological response after second vaccine dose (T2) regarding treatment and tumour entity. Mean antibody titre in binding activity units per millilitre (BAU/ml) for T2 is shown in relation to tumour entities and treatment. Tumour entity was differentiated into patients with lymphoma or chronic lymphoid leukaemia (CLL), patients with other haematological malignancies, and patients with underlying solid cancer. These groups were divided into patients under treatment and patients under close surveillance (no treatment). The number of patients (n) in each group is shown. The indicated P value between treatment groups is reported using analysis of variance (ANOVA).

Fig 4

The spike protein receptor binding domain (S/RBD)‐antibody response with respect to natural killer (NK)‐cell count, lymphocytes count and immunoglobulin G (IgG) level. Patients with baseline NK‐cell count and lymphocytes count below and above the lower reference value (74 cell/µl for NK cells and 0·7 g/l for lymphocytes) are presented according to the percentage of patients with serological response (detectable S/RBD‐ antibodies >0·82 binding activity units per millilitre [BAU/ml]) using cross tabulation. Patients with IgG > and ≤550 mg/dl are also differentiated by percentage of serological response. The number of cases in the different groups are given in numbers (n).

Fig 5

Occurrence of local and systemic side‐effects (within 7 days of vaccination). Relative incidence of local and systemic adverse events are expressed as percentages, at 1 week and 5 weeks after the first dose. Thus, side‐effects for the 7 days following each dose are displayed and differentiated by severity using the Common Terminology Criteria of Adverse Events (CTCAE). No Grade IV or V adverse reactions were reported.