Skin complications associated melanoma treatment with nivolumab or pembrolizumab

This study investigated the negative effects on the skin associated with the use of nivolumab (Opdivo) to treat melanoma. Researchers suggested that skin complications are the most frequent side effects but they are in most cases manageable.

The use of PD-1 antibodies, such as nivolumab (Opdivo) or pembrolizumab (Keytruda), to treat melanoma is rapidly increasing. These treatments stimulate the immune system to attack cancer cells the way it would a virus or bacteria. However, this therapy is associated with skin negative effects. Studies have reported that 40% of patients experience skin side effects. These effects are in most cases manageable. Although nivolumab is considered to be less toxic than ipilimumab (Yervoy, an antibody that targets a different protein), prior studies suggested similar rates of skin side effects in both therapies.

The objective of this review was to investigate rates of skin complications associated with the use of PD-1 antibodies. 

13-22% of melanoma patients treated with nivolumab experience skin rash (2% have a severe rash). In patients treated with ipilimumab the incidence was slightly higher (24.3%).

Macular papular rash (skin with a flat, red area covered with small bumps) and pruritus (general itchiness) are the most common types of rash. However, patients may also experience lichenoid dermatitis (purple bumps on the body that become itchy and swollen) and psoriasis (abnormal skin that becomes red and itchy). Early treatment of these side effects and adequate follow-up is important to avoid side effects progression and decrease of quality of life.     

Vitiligo (patches of skin that lose color) is also a well-known side effect of the treatment with PD-1 antibodies (8% to 25% of patients). Some studies have reported that this side effect is more common in treatment with PD-1 antibodies. It generally begins after a few months of treatment.

Xerosis (dry skin, skin peeling, itching and skin cracking) may also occur in 2-9% of patients treated with PD-1 antibodies.

Mucosal complications may also occur, such as inflammation of the mouth area. These effects appear to be less common in patients treated with ipilimumab.

Prior studies suggested that ipilimumab may reactivate an immune-related disease (when the immune system attacks healthy cells of the body), such as psoriasis. Treatment with PD-1 antibodies may also be responsible for the progression of pre-existing immune diseases.

The combination of nivolumab and ipilimumab is beneficial for melanoma treatment. However the combined treatment is associated with a higher rate of skin complications (59-71% of patients) when compared with nivolumab alone (42%) or ipilimumab alone (55%).

This study suggests that skin complications are the most common side effects of treatment with PD-1 antibodies. However they are easily manageable in most cases. Early treatment of these side effects is necessary to prevent a negative impact on patient quality of life.