Immunogenicity of COVID-19 vaccines in patients with hematologic malignancies: a systematic review and meta-analysis

Abstract

The objectives of this study were to assess the immunogenicity and safety of COVID-19 vaccines in patients with haematological malignancy. A systematic review and meta-analysis of clinical studies of immune responses to COVID-19 vaccination stratified by underlying malignancy and published from 1 January 2021 to 31 August 2021 was conducted using MEDLINE, EMBASE and CENTRAL. Primary outcome was the rate of seropositivity following 2 doses of COVID-19 vaccine with rates of seropositivity following 1 dose, rates of positive neutralising antibody (nAb), cellular responses and adverse events as secondary outcomes. Rates were pooled from single arm studies while rates of seropositivity were compared against the rate in healthy controls for comparator studies using a random effects model and expressed as a pooled odds ratio with 95% confidence intervals. Forty-four studies (16 mixed group, 28 disease specific) with 7064 patients were included in the analysis (2331 following first dose, 4733 following second dose). Overall seropositivity rates were 61-67% following 2 doses and 37-51% following 1 dose of COVID-19 vaccine. The lowest seropositivity rate was 51% in CLL patients and was highest in patients with acute leukaemia (93%). Following 2 doses, nAb and cellular response rates were 57-60% and 40-75% respectively. Active treatment, ongoing or recent treatment with targeted and CD-20 monoclonal antibody therapies within 12 months was associated with poor COVID-19 vaccine immune responses. New approaches to prevention are urgently required to reduce COVID-19 infection morbidity and mortality in high-risk patient groups that respond poorly to COVID-19 vaccination.

Early Cellular and Humoral Responses Developed in Oncohematological Patients after Vaccination with One Dose against COVID-19

“…Therefore, although individuals with CLL showed the highest levels of B cells due to the disease, significant alteration of B cell subpopulations was found, such as the reduction of naïve and resting memory B cells, which would entail an altered B cell activity and the reduced levels of seroconversion. Conversely, the excellent early humoral response (90% of seroconversion rate) developed by individuals with CML after one-dose vaccination against SARS-CoV-2, despite the B cell lymphopenia, was in accordance with previous studies that described good seroconversion rates among patients with chronic MPN and CML [ 45 ], being 54–71% after one single dose of vaccine [ 43 ]. This difference in the humoral responses between CLL and CML may also be related to the potent immunomodulatory effect induced in the latter during treatment with TKIs [ 19 ], which may be conserved even after several years of discontinuing treatment [ 46 ] and would explain the low hospitalization rate described for individuals with CML on TFR due to COVID-19 [ 6 ].…”

“…The seroconversion rates in our cohorts were variable depending on each OHD, being under the limit of detection in individuals with CLL but excellent in individuals with CML, who showed significantly higher IgG titers than healthy donors. Other studies corroborate this low seroconversion rates for CLL patients, estimated at 18% following a single dose [ 43 ] and that is most likely influenced by the severe B cell impairment in CLL patients treated with B cell depleting or targeted therapies such as anti-CD20 or BTK inhibitors [ 39 , 44 ]. Therefore, although individuals with CLL showed the highest levels of B cells due to the disease, significant alteration of B cell subpopulations was found, such as the reduction of naïve and resting memory B cells, which would entail an altered B cell activity and the reduced levels of seroconversion.…”

Efficacy and safety profile of COVID-19 mRNA vaccine in patients with hematological malignancies: Systematic review and meta-analysis

“…The same concern is also directed at patients with hematological malignancies, especially due to their high risk of being immunosuppressed due to the pathogenesis and molecular mechanism of the disease. One study has mentioned the lower positive seropositivity rate ranging from 62%–66% in patients with hematological malignancies, those with B-cell malignancies, and those undergoing active monoclonal antibody treatment ( 11 ). The response rate of COVID-19 vaccines in hematological malignancies is also lower than the solid cancer group by almost two fold ( 12 ).…”

Vaccination for the Prevention of Infection among Immunocompromised Patients: A Concise Review of Recent Systematic Reviews

“…In contrast, patients with receipt of anti-CD20 therapy [ 18 ] and solid organ transplants [ 11 , 19 , 20 ] (thus requiring anti-rejection immunosuppression) had markedly low vaccine seroconversion rates (rates ranged from about 26% to 45% after two vaccine doses). Patients with hematologic cancers had intermediate seroconversion rates (rates ranged from about 54% to 65%) [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. An intervention that improved vaccine efficacy was the use of additional booster vaccine doses [ 20 ].…”