Neuropsychological and central neurologic effects of cancer immunotherapy: the start of a new challenge.

Abstract

Introduction: Cognitive difficulties are frequently reported after cancer treatments, such as chemotherapy or hormone therapy, and have a negative impact on patients' quality of life. Recently, some studies have shown that new cancer treatments, such as immunotherapy agents, can induce cognitive changes.

Method: This review presents the central neurological immune adverse events of immunotherapy treatments including Immune Checkpoint Inhibitors (ICI) and Chimeric Antigen Receptor (CAR) T-cell therapy. The physiopathological mechanisms and risk factors are developed and clinical studies on immunotherapy agents and cognition (among adult patients, using validated questionnaires and/or cognitive tests), psychological factors and quality of life were presented.

Results: Neurological toxicities are frequently observed with CAR-T cell therapies at acute stage, such as the immune effector cell-associated neurotoxicity syndrome (ICANS), inducing cognitive disorders such as disorientation and aphasia. However, few studies have accurately assessed the impact of immunotherapy on cognition. The methodology of these studies is heterogeneous and they mainly included nonspecific self-report questionnaires of cognitive complaints. Variable results have been obtained concerning the cognitive impact of ICI and CAR-T cell several months following immunotherapy: overall, while some studies reported cognitive difficulties (mainly processing speed and executive functions), the majority has not. Although anxiety and depression are frequently reported in patients treated with ICI or CAR-T cells, these symptoms tend to decrease after the start of immunotherapy. The current neurobiological investigations are too fragmentary to explain neurological symptoms and potential cognitive alteration, but neuroinflammation, vascular inflammation, brain blood barrier disruption, and immune cell brain infiltration would constitute common mechanisms relayed by CAR-T and to a lesser degree, ICI.

Conclusions: Acute neurological toxicities following CAR-T cell therapies are a major issue. Further studies are needed to better assess cognitive difficulties after the initiation of immunotherapy, in particular ICI, to better understand the physiopathology, including imaging studies, and risk factors.