Risk of infection in patients with hematological malignancies receiving CAR T-cell therapy: systematic review and meta-analysis

Abstract

Background Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment option for relapsed or refractory B-cell malignancies and multiple myeloma. Various factors —underlying immune dysfunction, prior chemotherapy, lymphodepletion, prolonged cytopenias, hypogammaglobulinemia and use of corticosteroids and tocilizumab— may contribute to the development of infectious complications. Research design and methods We conducted a systematic review and meta-analysis on the incidence of overall and severe (grade ≥3) infection in patients with hematological malignancies receiving CAR T-cells. Secondary outcomes included the specific rates of bacterial, viral and invasive fungal infection (IFI), and infection-related mortality. PubMed, Embase and Web of Science databases were searched from inception to May 27, 2022. Sensitivity analysis were performed according to the type of malignancy and study design (randomized clinical trials [RCTs] or observational studies). Results Forty-five studies (34 RCTs) comprising 3,591 patients were included. The pooled incidence rates of overall and severe infection were 33.8% (I2 = 96.31%) and 16.2% (I2 = 74.41%). The respiratory tract was the most common site of infection. Most events were bacterial or viral, whereas the occurrence of IFI was rare. The pooled attributable mortality was 1.8% (I2 = 43.44%). Conclusions Infection is a frequent adverse event in patients receiving CAR T-cell therapy. Further research should address specific risk factors in this population.