In patients with haematological malignancy, the immune response to SARS-CoV-2 is impaired and vaccines are thus an important preventive option. However, patients with haematological malignancies display reduced antibody responses rates to SARS-CoV-2 vaccine, particularly for those with chronic lymphocytic leukaemia and aggressive or indolent non-Hodgkin lymphoma. The humoral response to vaccination was further affected by remission status, history of COVID-19, and treatment.
For patients with haematological malignancies, the risk of death among adult patients who had coronavirus disease 2019 (COVID-19) was estimated to be 34% in predominantly hospitalised patients. Similarly, patients undergoing haematopoietic cell transplantation or cellular therapy were found to be at increased risk for lower respiratory tract disease, intensive care admission, and death. In addition, COVID-19 elicits an impaired antibody response against SARS-CoV-2 in haematological malignancies. Overall, this emphasised the need for stringent surveillance and urgent identification of therapeutic and preventive options. Vaccines against SARS-CoV-2 have shown remarkable efficacy and, therefore, constitute an important preventive option against COVID-19, especially in fragile patients. However, the actual effect in patients with haematological malignancies and transplantation/cellular therapy is unclear. This study aimed to systematically analyse the outcomes of patients with haematological malignancies who received vaccination, and to identify specific groups with differences in outcomes.
This study followed the updated Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline and the Meta-analysis of Observational Studies in Epidemiology (MOOSE) checklist. All studies published since 1 July 2020 on adults with haematological malignancies (myeloid, lymphoid, or plasma cell dyscrasias) after one or two doses of vaccine were considered for inclusion. Full vaccination was defined as two doses of mRNA vaccination or one dose of vector-based vaccines. Case reports/series or cohort studies with an overall population of less than ten were excluded. Patients were categorised as in remission or at stable/progressive disease at the time of COVID-19 vaccination. The primary endpoint was antibody response (seroconversion rate) after full vaccination (one or two doses, depending on the vaccine), as assessed by anti-SARS-CoV-2 spike protein IgG antibody testing. The secondary endpoints were efficacy, response after first dose, and safety. A Q test was used to assess between-study heterogeneity and calculated the I² statistic, which expresses the percentage of the total observed variability caused by study heterogeneity. I² values were defined as low (≤50%), moderate (50-75%), or high heterogeneity (>75%). Publication bias was assessed by visual inspection of the funnel plots, coupled with the Egger’s test.
This meta-analysis included 49 studies comprising 11,086 individuals. Overall risk of bias was low. In total, 39 studies reported on antibody response after full vaccination (mostly second dose of mRNA vaccines). A significant between-group difference in antibody response was identified between haematological malignancies, solid cancer, and healthy control (p<0.001). The pooled response for haematological malignancies was 64%, with high heterogeneity (I²= 93%). In contrast, the pooled response for solid cancer was 96% with no heterogeneity (I²= 44%), and this was 98% with moderate heterogeneity for healthy controls (I²= 55%). The outcome also varied across haematological malignancies (p< 0.001). The pooled response was 50% (I²= 84%) for chronic lymphocytic leukaemia, 76% (I²= 92%) for multiple myeloma, 83% (I²= 85%) for myeloproliferative neoplasms, and 58% (I²= 84%) for aggressive and 61% (I²= 85%) for indolent non-Hodgkin lymphoma. Only patients with Hodgkin lymphoma appeared to exhibit comparable responses to healthy controls, showing pooled response of 91% (I²= 12%). Pooled responses were 72% vs. 48% for patients in remission and those with stable or progressive disease, respectively. Heterogeneity was high (I2= 80% and 93%). Antibody response was furthermore affected by history of COVID-19 prior to vaccination, and these patients showed pooled response of 87% with no heterogeneity (I2= 26%). The pooled response for allogeneic and autologous haematopoietic cell transplantation was 82% and 83%, with moderate (I2= 64%) and high (I2= 83%) heterogeneity, respectively. A significant difference in antibody response was found for active treatment at time of vaccination in comparison with no treatment. Patients showed a pooled response of 35% vs. 76% (I2= 93% and 83%). Furthermore, targeted treatments were evaluated. Low pooled response was identified for anti-CD20 therapy ≤1 year (15%), Bruton kinase inhibition (23%), venetoclax (26%), ruxolitinib (42%), and chimeric antigen receptor T-cell therapy (42%). The efficacy of vaccination during follow-up was also assessed. The pooled proportion of evaluable patients without COVID-19 during follow-up was 99%, and no heterogeneity was observed (I²= 23%). In terms of safety, one-third of patients reported local adverse events such as injection side pain and sore arm. Most frequent systemic adverse events were weakness/fatigue (6-30%) and generalised muscle pain (4-30%).
This meta-analysis included more than 11,000 patients with haematological malignancies, solid cancer, or healthy controls and analysed antibody responses after vaccination against SARS-CoV-2. Markedly reduced response rates were found for patients with haematological malignancies. In terms of disease subgroups, patients with chronic lymphocytic leukaemia showed lowest pooled response rates, followed by patients with aggressive or indolent non-Hodgkin lymphoma. The humoral response to vaccination was further affected by remission status, history of COVID-19, and treatment.
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