Immune-Related Adverse Effects of Cancer Immunotherapy- Implications for Rheumatology

Abstract

Immune checkpoint inhibitors (ICIs) are increasingly studied and used as therapy for a growing number of malignancies. ICIs work by blocking inhibitory pathways of T-cell activation, leading to an immune response directed against tumors. Such nonspecific immunologic activation can lead to immune-related adverse events (IRAEs). Some IRAEs, including inflammatory arthritis, sicca syndrome, myositis, and vasculitis, are of special interest to rheumatologists. As use of ICIs increases, recognition of these IRAEs and developing treatment strategies will become important. In this review, the current literature on rheumatic and musculoskeletal IRAEs is summarized. The incidence, clinical presentations, and treatment considerations are highlighted.

Keywords: Arthritis; Immune checkpoint inhibitors; Immune-related adverse events; Malignancy; Sicca syndrome.

Figure 1

Mechanism of action for immune checkpoint inhibition targeting CTLA-4 and PD-1. A) Inhibition of T-cell activation by interactions with tumor cells and antigen presenting cells (APC). PD-L1 and PD-L2 on tumor cells and APCs bind to PD-1 on the T-cell and B7 on APCs binds to CTLA-4 on the T-cell. B) Antibodies to PD-1 or CTLA-4 block inhibitory interactions, allowing for positive co-stimulation (B7 binds CD28)

Figure 2

Proposed treatment algorithm. If patients do not respond within 4 to 6 weeks of therapy, escalate to next level of treatment.