Infections following CAR-T cells therapy: current state-of-the-art review and recommendations

Abstract

The most frequent and severe complications after chimeric antigen receptor T-cells (CAR-T cells) therapy include cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), macrophage activation syndrome/hemophagocytic lymphohistiocytosis (MAS/HLH), tumor lysis syndrome (TLS), followed by B-cell aplasia and hypogammaglobulinemia. With these immunologically related events, cytokine storm and immunosuppression, there is a high risk of sepsis and infectious complications. The objective of this review was to present current knowledge on incidence, risk factors, clinical characteristics, and outcome of infections in patients following CAR-T cells therapy, as well as to present current recommendations on prophylaxis of infections after CAR-T cells therapy. Comparable to hematopoietic cell transplantation setting, specific pre- and post-CAR-T cells infusion phases can be determined as early (from 0 to +30 days), intermediate (from +31 to +100 days), and late (beyond day +100). These phases are characterized by CAR-T cells therapy-related factors and immune system defects contributing to an increased risk of infections. It is recommended that in case of active infection, CAR-T cells infusion should be delayed until infection has been successfully treated. After CAR-T cells therapy, prophylaxis should be implemented (anti-bacterial, anti-viral, anti-fungal, anti-pneumocystis), as well as treatment of neutropenia and immunoglobulin replacement should be considered. No recommendations so far can be given on revaccinations after CAR-T cells therapy.

Cytomegalovirus in Haematological Tumours

“…The European recommendations are based on data from allogeneic transplant recipients ( 133 ). In general, antiviral prophylaxis is established with acyclovir or valacyclovir at least up to one year after CAR-T infusion, or until a CD4+ T lymphocyte level greater than 0.2 x 10 9 /L is documented ( 134 ). In paediatrics, nonspecific immunoglobulins are also frequently used to maintain total IgG levels above 0.4 g/L ( 135 ).…”

Where dreams come true: CAR-T cell therapy in Poland!

“…therapy [2,3,4]. So far, it is feasible only for B-cell lineage hematological malignancies, but the door has been opened for further research and progress.…”

CAR‐T cell therapy in paediatric acute lymphoblastic leukaemia – past, present and future

“…46 Cytopaenias and subsequent infections have been related to the severity of CRS. 69,70 Approximately 20-40% of patients will develop infection within first month following CAR-T cell therapy. 64 The increased incidence of infection in children and young adults seems to decrease after the first 4 months.…”

“…Current paediatric practice is to replace immunoglobulin with a threshold of 5 g/l. However, prospective data on immunoglobulin replacement after CAR‐T cell therapy is lacking 64,70 …”

“…Cytopaenias and subsequent infections have been related to the severity of CRS 69,70 . Approximately 20–40% of patients will develop infection within first month following CAR‐T cell therapy 64 .…”