Evaluating the risk of lung inflammation associated with immunotherapy in advanced melanoma.

This study evaluated the risk of pneumonitis (inflammation of the lung tissue) associated with immune checkpoint inhibitors (ICIs) for the treatment of patients with advanced melanoma. The data showed that ICIs were associated with a higher risk of pneumonitis compared with conventional chemotherapy in patients with advanced melanoma.

Melanoma is an aggressive type of skin cancer. It has a high tendency to spread to other parts of the body (metastasis). The standard treatment for advanced melanoma is a combination of immunotherapy, chemotherapy, surgical removal of tumors, and radiation therapy.

Immunotherapy uses the body’s own system to fight against cancer cells. Tumor cells try to avoid death by switching off our immune system. They bind to proteins on the surface of the immune cells such as PD-1/PD-L1 or CTLA-4.  ICIs such as pembrolizumab (Keytruda), nivolumab (Opdivo), and ipilimumab (Yervoy) block these interactions and turn on the immune system to attack and kill the cancer cells.

The most common side effects associated with immunotherapy are known as immune-related adverse events (irAEs). These events often include skin rashes or inflammation in areas such as the lungs, intestines, or thyroid. One rare irAE is the development of immune-related pneumonitis (IRP). Pneumonitis is a dangerous and potentially deadly swelling of the lungs and lung tissue. However, there are few studies evaluating the risk of pneumonitis associated with ICIs for the treatment of patients with advanced melanoma.

This study analyzed 10 studies that involved 5,335 patients with advanced melanoma. Patients were divided into 4 groups according to the treatment combination they received. 59.1% of the patients received ICIs only (monotherapy). 18.2% of the patients received dual ICIs (2 ICIs) combination. 13.6% of the patients received chemotherapy. 9.1% of the patients received a placebo.

Conventional chemotherapy was associated with a lower risk (by 86%) of pneumonitis compared with ICI monotherapy. Conventional chemotherapy was also associated with a lower risk (by 99.97%) of pneumonitis compared with dual ICIs combination.

Dual ICIs combination was associated with a 4.45 times higher risk of pneumonitis compared with ICIs monotherapy.

No significant difference in pneumonitis risk was found between CTLA-4 and PD-1 inhibitors.

This study concluded that ICIs were associated with a higher risk of pneumonitis compared with conventional chemotherapy for the treatment of patients with advanced melanoma.

The definition of IRP was not consistent in different studies. The identification of IRP might not be accurate and complete. Patients in 30% of the studies knew which type of treatment they were getting.