Immune checkpoint inhibitors (ICIs) are at the forefront of advances in cancer therapy and have shown promising results for progression-free survival. Checkpoint signaling pathways, such as cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1), normally regulate the immune response to promote self-tolerance and prevent tissue damage and inflammation.
Explore this issueSeptember 2018
PD-1 is a co-inhibitory receptor expressed on activated T cells. It “turns off” T cells that would normally destroy cancer cells. Solid tumors have increased expression of PD-1, which is often associated with a worse prognosis. Blockage of PD-1 with ICIs enhances T cell function and tumor lysis. This is the basis of using monoclonal antibodies to PD-1 inhibitors as targeted immunotherapy cancer agents.1,2
PD-1 inhibition not only enhances the immune response to tumor cells but also to normal host tissue. Immune-related adverse events (irAEs) from ICIs occur from self-intolerance with inhibition of checkpoint sites and uncontrolled activity of T cells, leading to a multi-organ inflammatory response that can mimic a rheumatologic condition. irAEs, graded 1–4, can occur in variable frequency at any time during therapy. They have been reported in higher numbers with the use of CTLA4 inhibitors, such as ipilimumab, or combination PD1 inhibitors (e.g., nivolumab, pemrolizumab) but less commonly with nivolumab monotherapy.2,3 Nivolumab (Opdivo) has been approved for melanoma, squamous cell cancer of the head and neck, Hodgkin’s lymphoma, colorectal, renal cell and non-small cell lung cancer.
irAEs can involve any organ system, but myalgias, arthralgias, gastrointestinal, dermatologic, hepatic and endocrine autoimmune effects are those most commonly reported with nivolumab use. Cardiac, pulmonary and ocular toxicities are rare.3-5