Fatal adverse events associated with PD-L1 inhibitors

What are PD-L1 inhibitors?

PD-L1 (programmed cell death ligand 1) inhibitors are a group of checkpoint inhibitors being developed for the treatment of cancer. It is protein present on the surface of cells. Immune checkpoint inhibitors such as these are emerging as a front-line treatment for several types of cancer.

Examples of PD-L1 inhibitors: 

• Atezolizumab (Tecentriq) is a fully humanised IgG1 (immunoglobulin 1) antibody approved for urothelial carcinoma and non-small cell lung cancer.
• Avelumab (Bavencio) is a fully human IgG1 antibody approved for the treatment of metastatic merkel-cell carcinoma. It failed phase III clinical trials for gastric cancer.
• Durvalumab (Imfinzi) is a fully human IgG1 antibody approved for the treatment of urothelial carcinoma and unresectable non-small cell lung cancer after chemoradiation.

What are  checkpoint inhibitors ? 

An important function of the immune system is its ability to tell between normal cells in the body and those it sees as “foreign.” This lets the immune system attack the foreign cells while leaving the normal cells alone. To do this, it uses “checkpoints.” Immune checkpoints are molecules on certain immune cells that need to be activated (or inactivated) to start an immune response.

Cancer cells sometimes find ways to use these checkpoints to avoid being attacked by the immune system. But drugs that target these checkpoints hold a lot of promise as cancer treatments. These drugs are called checkpoint inhibitors.

It’s important to know that checkpoint inhibitors used to treat cancer don’t work directly on the tumor at all. They only take the brakes off an immune response that has begun but hasn’t yet been working at its full force.

Safety issue from meta analysis: 

A systematic review and meta-analysis was conducted in Fujian Medical University to assess the incidence of fatal adverse events that were associated with the use of PD-L1. Total 6,896 unique patients were studied and total 84 deaths were identified associated with PD-L1 inhibitors. 

Study reports states “The incidence were higher in patients with non-squamous non-small cell lung cancer (NSCLC) than those with urothelial carcinoma, higher in the middle-aged group than the young group. In terms of organ-specific fatal adverse events, interstitial lung disease (ILD) was frequently documented. A variety of respiratory system-related fatal adverse events were recorded, including but not limited to pneumonia and respiratory failure. As for organ-unspecific fatal adverse events, substantial cases of sepsis and neutropenia were recorded”.