Immunogenicity and risks associated with impaired immune responses following SARS-CoV-2 vaccination and booster in hematologic malignancy patients: an updated meta-analysis

Patients with hematologic malignancies (HM) have demonstrated impaired immune responses following SARS-CoV-2 vaccination. Factors associated with poor immunogenicity remain largely undetermined. A literature search was conducted using PubMed, EMBASE, Cochrane, and medRxiv databases to identify studies that reported humoral or cellular immune responses (CIR) following complete SARS-CoV-2 vaccination. The primary aim was to estimate the seroconversion rate (SR) following complete SARS-CoV-2 vaccination across various subtypes of HM diseases and treatments. The secondary aims were to determine the rates of development of neutralizing antibodies (NAb) and CIR following complete vaccination and SR following booster doses. A total of 170 studies were included for qualitative and quantitative analysis of primary and secondary outcomes. A meta-analysis of 150 studies including 20,922 HM patients revealed a pooled SR following SARS-CoV-2 vaccination of 67.7% (95% confidence interval [CI], 64.8-70.4%; I-2 = 94%). Meta-regression analysis showed that patients with lymphoid malignancies, but not myeloid malignancies, had lower seroconversion rates than those with solid cancers (R-2 = 0.52, P < 0.0001). Patients receiving chimeric antigen receptor T-cells (CART), B-cell targeted therapies or JAK inhibitors were associated with poor seroconversion (R-2 = 0.39, P < 0.0001). The pooled NAb and CIR rates were 52.8% (95% CI; 45.8-59.7%, I-2 = 87%) and 66.6% (95% CI, 57.1-74.9%; I-2 = 86%), respectively. Approximately 20.9% (95% CI, 11.4-35.1%, I-2 = 90%) of HM patients failed to elicit humoral and cellular immunity. Among non-seroconverted patients after primary vaccination, only 40.5% (95% CI, 33.0-48.4%; I-2 = 87%) mounted seroconversion after the booster. In conclusion, HM patients, especially those with lymphoid malignancies and/or receiving CART, B-cell targeted therapies, or JAK inhibitors, showed poor SR after SARS-CoV-2 vaccination. A minority of patients attained seroconversion after booster vaccination. Strategies to improve immune response in these severely immunosuppressed patients are needed.