PD-1 and PD-L1 inhibitor toxicities in non-small cell lung cancer

Immune checkpoint inhibitors (ICIs) utilize the natural programming of the immune system to initiate an antitumor response, counteracting checkpoint molecule expression on tumor cells (1). Immunotherapies that inhibit the programmed death 1 (PD-1) molecule, the programmed death ligand 1 (PD-L1) molecule, and the cytotoxic lymphocyte antigen 4 (CTLA-4) molecule have demonstrated improved survival outcomes for patients with renal cell carcinoma (2), advanced melanoma (3), and non-small cell lung cancer (NSCLC) (4-11). ICIs are a relatively recent therapeutic strategy in cancer that may produce off-target effects due to inflammation in various organ systems. These effects are defined as immune-related adverse events (irAEs), and though are rare occurrences, can be fatal (12). The toxicities associated with PD-1 and CTLA-4 inhibition reported thus far include skin rashes, diarrhea and colitis, thyroid dysfunction, type I diabetes mellitus, and pneumonitis (1). Pneumonitis is a particularly concerning adverse effect of ICI therapy because of its potentially fatal outcomes in patients treated with anti-PD-1/PD-L1 ICIs for cancer (13)