Vaccinations in hematological patients in the era of target therapies: Lesson learnt from SARS-CoV-2

Novel targeting agents for hematologic diseases often exert on- or off-target immunomodulatory effects, possibly impacting on response to anti-SARS-CoV-2 vaccinations and other vaccines. Agents that primarily affect B cells, particularly anti-CD20 monoclonal antibodies (MoAbs), Bruton tyrosine kinase inhibitors, and anti-CD19 chimeric antigen T-cells, have the strongest impact on seroconversion. JAK2, BCL-2 inhibitors and hypomethylating agents may hamper immunity but show a less prominent effect on humoral response to vaccines. Conversely, vaccine efficacy seems not impaired by anti-myeloma agents such as proteasome inhibitors and immunomodulatory agents, although lower seroconversion rates are observed with anti-CD38 and anti-BCMA MoAbs. Complement inhibitors for complement-mediated hematologic diseases and immunosuppressants used in aplastic anemia do not generally affect seroconversion rate, but the extent of the immune response is reduced under steroids or anti-thymocyte globulin. Vaccination is recommended prior to treatment or as far as possible from anti-CD20 MoAb (at least 6 months). No clearcut indications for interrupting continuous treatment emerged, and booster doses significantly improved seroconversion. Cellular immune response appeared preserved in several settings.