A Systematic Review and Meta-analysis of Immune Response Against First and Second Doses of SARS-CoV-2 Vaccines in Adult Patients with Hematological Malignancies

Background: Cancer patients particularly those with hematological malignancies are at higher risk of affecting by severe coronavirus disease 2019 (COVID-19). Due to the immunocompromised nature of the disease and the immunosuppressive treatments, they are more likely to develop less antibody protection; therefore, we aimed to evaluate the immunogenicity of COVID-19 vaccines in patients with hematological malignancies.

Methods: A comprehensive systematic search was conducted in PubMed, Scopus, and Web of Science databases, as well as Google scholar search engine as of December 10, 2021. Our primary outcomes of interest comprised of estimating the antibody seropositive rate following COVID-19 vaccination in patients with hematological malignancies and to compare it with those who were affected by solid tumors or healthy subjects. The secondary outcomes were to assess the vaccine's immunogenicity based on different treatments, status of the disease, and type of vaccine. After the two-step screening, the data were extracted and the summary measures were calculated using a random-effect model.

Results: A total of 82 articles recording 13,804 patients with a diagnosis of malignancy were included in the present review. The seropositive rates in patients with hematological malignancies after first and second vaccine doses were 30.0% (95% confidence interval (95%CI): 11.9-52.0) and 62.3% (95%CI 56.0-68.5), respectively. These patients were less likely to develop antibody response as compared to cases with solid tumors (RR 0.73, 95%CI 0.67-0.79) and healthy subjects (RR 0.62, 95%CI 0.54-0.71) following complete immunization. Chronic lymphocytic leukemia (CLL) patients had the lowest response rate among all subtypes of hematological malignancies (first dose: 22.0%, 95%CI 13.5-31.8 and second dose: 47.8%, 95%CI 41.2-54.4). Besides, anti-CD20 therapies (5.7%, 95%CI 2.0-10.6) and bruton's tyrosine kinase inhibitors (26.8%, 95%CI 16.9-37.8) represented the lowest seropositiveness post first and second doses, respectively. Notably, patients who were in active status of disease showed lower antibody detection rate compared to those on remission status (RR 0.87, 95%CI 0.76-0.99). Furthermore, lower rate of seropositivity was found in patients received BNT162.b2 compared to ones who received mRNA-1273 (RR 0.89, 95%CI 0.79-0.99).

Conclusion: Our findings highlight the substantially low rate of seroprotection in patients with hematological malignancies with a wide range of rates among disease subgroups and different treatments; further highlighting the fact that booster doses might be acquired for these patients to improve immunity against SARS-CoV-2.