Vaccinations following CAR-T cell therapy: summary of reported cases and state-of-the-art review of current recommendations

Abstract

Introduction: Chimeric antigen receptor T-cell (CAR-T) therapy is a modern breakthrough technology used in the treatment of B-lineage lymphoid malignancies. These malignancies include acute lymphoblastic leukemia, non-Hodgkin lymphoma, and plasma cell disorders. CAR-T therapy combines cellular therapy, gene therapy, and individualized therapy. The objective of this paper was to review the latest clinical knowledge, and summarize the reported data pertaining to vaccinations in patients after CAR-T therapy. Material and methods: We carried out a review of published original studies as indexed in PubMed, and a review of abstracts presented during major hematology meetings. Results: Overall, 22 original studies were reviewed and considered suitable for analysis regarding the efficacy of vaccinations for patients who had received CAR-T therapy. Data was divided into three groupings: the efficacy of vaccination against coronavirus disease 2019 (COVID-19)/severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); the efficacy of vaccination against influenza; and the efficacy of post-CAR-T immunization persistence of vaccination performed before CAR-T therapy. Humoral and cellular response to SARS-CoV-2 vaccination was positive for 36.5% and 72.2% of patients, respectively. The positive response to the influenza vaccine was 40% when administered prior to CAR-T therapy, as opposed to 31% after. Seroprotection for vaccine-preventable infections within 3-6 months after CAR-T was comparable to that of the general population, although it was determined to be less effective against specific pathogens (S. pneumoniae, B. pertussis, H. influenzae) in most patients. Conclusions: In cases of incomplete immune reconstitution, there is a high likelihood of a limited response to vaccination. Regarding the SARS-CoV-2/COVID-19 vaccine, T-cell-induced protection is relatively significant. Therefore, B-cell aplasia is not a contraindication for vaccination in CAR-T patients. The consensus of European Society of Blood and Marrow Transplantation/European Hematology Association experts is that vaccination after CAR-T therapy is beneficial in order to reduce the rates of infection, and eventually to improve clinical course.

Kinetics of CAR-T cells and immunological profile after tisagenlecleucel therapy

“…Furthermore, the expansion of CAR-T cells happened at the same time as the occurrence of CRS and ICANS. It is still not fully understood whether the peak of CAR-T cells is the cause of the toxicities itself, or an effect of immune-related CAR-T cell expansion [4,6,7]. Incidences of those toxicities were associated also with an increase in both proinflammatory mediators (IL-6 and ferritin) and a slight increase in anti-inflammatory cytokines (IL-10).…”

Hematology and transfusion medicine journal of pediatric and adult diseases: we all are readers, authors and reviewers

“…In many aspects, achievements in hematology have preceded achievements in other disciplines, with the most obvious examples being the use of stem cells, monoclonal antibodies or targeted drugs. It is to be expected that chimeric antigen receptor T-cell (CAR-T) technology will be used also outside hematology in the future [3,9].…”

Very late relapse of ALL after 14 years: treatment with CAR-T cells

“…Therapy with CAR-T represents a new therapeutic possibility in patients with advanced refractory or relapsing ALL or non-Hodgkin lymphoma (NHL) [3][4][5][6].…”