Immunogenicity of the BNT162b2 COVID-19 mRNA vaccine and early clinical outcomes in patients with haematological malignancies in Lithuania: a national prospective cohort study

Abstract

Background Haematological malignancies and their treatments are likely to affect SARS-CoV-2 vaccine efficacy. We aimed to evaluate serological response to BNT162b2 vaccine in patients with haematological malignancies by type of treatment. Methods Our national prospective cohort study was done in Lithuania and assessed serological response to one and two BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccine doses in healthy health-care workers and in patients with haematological malignancies. Eligible participants were aged 18 years or older, had received both vaccine doses, and had available biobanked blood samples from before vaccination and after the second dose. Biobanked samples and health data were obtained from Vilnius University Hospital Santaros Klinikos Biobank. Abbott Architect SARS-CoV-2 IgG Quant II chemiluminescent microparticle assay was used to quantify serum anti-SARS-CoV-2-S1 IgG antibody (anti-S1 IgG antibody) concentrations 0–10 days before the first BNT162b2 vaccine, on the day of second immunisation (around day 21), and 7 to 21 days after the second immunisation. Adverse events were assessed by a standardised questionnaire. Breakthrough infections were characterised clinically and by SARS-CoV-2 genotyping whenever possible. This study is registered with ClinicalTrials.gov , NCT04871165 . Findings Between Jan 8 and April 21, 2021, 885 participants with haematological malignancies were included in the study. 857 patients were anti-S1 IgG seronegative at timepoint 0 and constituted the main analysis cohort. The age-matched comparison was made between 315 patients with haematological malignancies who were aged 18–60 years and 67 healthy health-care workers in the same age group. Patients aged 18–60 years with haematological malignancies had lower median anti-S1 IgG antibody responses after two BNT162b2 vaccine doses than did health-care workers of the same age group (median 6961 AU/mL [IQR 1292–20 672] vs 21 395 AU/mL [14 831–33 553]; p<0·0001). Compared with untreated patients with haematological malignancies (n=53; median 5761 AU/mL [629–16 141]), patients actively treated with Bruton tyrosine kinase inhibitors (BTKIs; n=44; 0 AU/mL [0–7]; p<0·0001), ruxolitinib (n=16; 10 AU/mL [0–45]; p<0·0001), venetoclax (n=10; 4 AU/mL [0–1218]; p=0·0005), or anti-CD20 antibody therapy (n=87; 17 AU/mL [1–2319]; p<0·0001) showed particularly poor anti-S1 IgG antibody responses following two BNT162b2 doses. Patients being treated with tyrosine kinase inhibitors (n=41; 10 537 AU/mL [IQR 2335–19 388]) or patients who received autologous haematopoietic stem-cell transplantation (HSCT; n=192; 6203 AU/mL [1451–16 834]) or allogeneic HSCT (n=122; 6304 AU/mL [1120–16 913]) were among the subgroups with the highest numerical responses. Nine SARS-CoV-2 infections and three COVID-19 deaths were observed among fully vaccinated patients with haematological malignancies. ...

Efficacy of the mRNA-Based BNT162b2 COVID-19 Vaccine in Patients with Solid Malignancies Treated with Anti-Neoplastic Drugs

“…Our results are consistent with those reported for immunosuppressed populations such as patients with chronic lymphocytic leukemia [14], and organ transplant recipients [32]. Immunosuppression has been shown to decrease the immune response in other vaccine studies, and particularly in patients with hematological malignancies who developed severely diminished antibody responses compared with healthy individuals [14][15][16]. These populations are at increased risk of SARS-CoV-2 infection despite vaccination.…”

“…The Centers for Disease Control and Prevention (CDC) recommends that vaccination be delivered 2 weeks prior to immunosuppressive therapy [12], but this is not possible in patients already on chemotherapy [12,13]. Several new studies raised concerns about the blunted antibody responses to the COVID-19 vaccine in patients with hematological malignancies [14][15][16]. A recent study reported that the BNT162b2 vaccine does have an acceptable short-term safety profile in patients treated with immune checkpoint inhibitors [17], but data on the efficacy of the vaccine in cancer patients with solid malignancies treated with anti-neoplastic drugs are scarce [18,19].…”

Antibody response after third BNT162b2 dose in recipients of allogeneic HSCT

“… 1 Similarly, in one large study of 885 patients with haematological malignancies, including patients who had and had not undergone transplantation, the treatments actively received at time of vaccination were the primary determinants of the antibody response. 9 Nine cases of breakthrough severe SARS-CoV-2 infections were reported in this previous study, which we did not observe in the present study, occurring in fully vaccinated patients who had mostly low anti-S-RBD IgG antibody titres.…”

Humoral and cellular responses to mRNA vaccines against SARS-CoV-2 in patients with a history of CD20 B-cell-depleting therapy (RituxiVac): an investigator-initiated, single-centre, open-label study

“…Our report adds to the results of a series of studies that have investigated humoral and cellular responses to SARS-CoV-2 vaccination in patients with a history of B-cell depleting anti-CD20 therapies. 11 , 12 , 16 , 28 , 29 , 30 , 31 Deepak and colleagues 11 first reported a 36-fold decrease in vaccine-induced anti-spike IgG titres in patients with B-cell depleting therapies. Simon and colleagues 30 and Apostolidis and colleagues 29 reported no detectable or severely diminished vaccine-induced humoral immune responses compared with controls in two smaller series of patients with severely depleted B-cell counts, but both studies reported detectable cell-mediated immunity in these patients.…”