Review of treatment-related adverse events from immunotherapies

The authors reviewed the treatment-related side effects associated with ipilimumab (Yervoy), pembrolizumab (Keytruda), and nivolumab (Opdivo) in melanoma. The authors found that a higher dose of ipilimumab was correlated with more side effects, but the same was not true for pembrolizumab and nivolumab.

In advanced melanoma (stages 3 and 4), cancer spreads from the skin to other parts of the body. Immunotherapy is a promising treatment option in these stages of the disease. It uses body’s own immune system to fight cancer. Ipilimumab, pembrolizumab, and nivolumab are examples of effective immunotherapies. These work by inhibiting/stopping important proteins in the immune system. This inhibition triggers the immune system to attack tumor cells and kill them. However, all of these immunotherapies are associated with moderate to severe and/or life threatening immune-related adverse events (irAEs).

Knowledge of the adverse events from immunotherapies in melanoma will help decide on the treatment options better.

Based on data from several phase 2 and phase 3 clinical trials of melanoma, the most common irAE was diarrhea. It affected 14-17% of patients receiving pembrolizumab, 11-19% of patients receiving nivolumab, 23-33% of patients receiving ipilimumab, and 44% of patients receiving a combination of ipilimumab and nivolumab. Skin-related adverse events such as rash, itching, and discoloration of skin were common from ipilimumab treatment. In a study among patients treated with ipilimumab, 24.3% developed a rash. 2.4% of these were severe or life threatening. Another study noted that 15-19% of melanoma patients experienced itching.

Other side effects noted included lung infections, thyroid dysfunction (which can cause fatigue and weight gain) and muscle pain.

Several studies indicated that ipilimumab at 10 mg/kg increased rates of irAEs in melanoma. In a trial comparing 10 mg/kg of ipilimumab with 3 mg/kg dose, 37% of patients experienced severe irAEs. 6% of patients experienced life-threatening toxicities. These toxicity rates are compared to 20-27% in patients treated with a 3 mg/kg dose. Rates of irAEs from nivolumab were not significantly different at 3 mg/kg and 10 mg/kg. Evaluation of long-term safety of nivolumab over 2 years did not show any increase in side effects.

The authors concluded that among the three immunotherapies reviewed, side effects from ipilimumab were dose-related. They further indicated that proper management of moderate to severe irAEs was important for long-term outcome of melanoma patients.