Rheumatic diseases associated with immune checkpoint inhibitors in cancer immunotherapy

Abstract

Immune checkpoint inhibitors (ICIs) have drastically altered cancer treatment paradigms, with increasing numbers of novel ICIs being currently evaluated in numerous clinical trials for various cancers. ICIs release ‘brakes’ against tumor immunity to control cancer growth through T cell-dependent anti-tumor activity. Meanwhile, side effects associated with ICIs are directly related to their mechanism of action, as nonspecific immune activation targeting non-tumor organs results in undesirable off-target inflammation and autoimmunity. Accumulating data reveal that immune-related adverse events (irAEs) of ICIs in cancer patients can resemble various rheumatic diseases. Moreover, while patients with preexisting rheumatic diseases can theoretically experience irAEs and disease flares, observational studies have shown that ICIs can be used successfully in these patients. As ICIs continue to provide long-lasting disease control in cancer patients and their usage correspondingly increases, the rheumatologist will be managing new ICI-associated clinical entities mimicking common autoimmune diseases and will need to be prepared to rapidly diagnose and treat these irAEs. Early recognition and treatment of these rheumatic adverse events will allow for improved outcomes and quality of life for cancer patients faced with previously rapidly fatal disease.

Keywords:

• Immune checkpoint inhibitor
• immune-related adverse events
• inflammatory arthritis
• rheumatic disease

Conflict of interest

None.

Additional information

Funding

This study was supported in part by a grant of the Ministry of Health, Labour, and Welfare, Japan [Grant Number 150401-01 (C.M.) and 180101-01 (C.M.)], JSPS KAKENHI Grant Numbers JP16H05345 (C.M.), JP18H02782 (K.O.), and JP17K10008 (R.H.).