Skin Cancer Diagnosis, Older Age May Be Associated With Increased Risk for Rare Skin Condition from Immunotherapy Treatment

Older age and having a diagnosis of skin cancer were associated with an increased risk of developing bullous pemphigoid, a rare blistering skin condition, in patients with cancer being treated with immune checkpoint inhibitors, according to research recently published in the journal JAMA Dermatology.

Researchers analyzed data from 2,955 patients with cancer who were treated with an immune checkpoint inhibitor at one of three large, Massachusetts-based cancer centers from 2014 to 2020. The findings showed that patients who were over the age of 70, or who had skin cancer — both melanoma and non-melanoma skin cancer — had an increased risk of bullous pemphigoid.

A total of 35 patients in the study population developed bullous pemphigoid during or after immune checkpoint inhibition treatment: 20 were aged 70 or older. Twelve patients with the condition had a diagnosis of melanoma, five had non-melanoma skin cancer and 18 had nonskin cancer.

Those with bullous pemphigoid were prescribed one of the following treatment regimens:

• Keytruda (pembrolizumab): 19 patients
• Opdivo (nivolumab): 14 patients
• Opdivo plus Yervoy (ipilimumab): 2 patients

While the relationship between age, immunotherapy and bullous pemphigoid is not clearly understood, the researchers noted that they think that it may have something to do with the drugs uncovering the condition in individuals who may already be susceptible to it.

“In the general population, the mechanistic association between age and (bullous pemphigoid) remains unclear; however, our findings in individuals treated with (immune checkpoint inhibitors) parallels the increased risk for idiopathic (bullous pemphigoid) in patients aged 70 years or older, suggesting that (immune checkpoint inhibitors) may exacerbate an underlying propensity for BP development in older individuals,” the authors wrote.

Bullous pemphigoid is a rare skin condition that can often cause mouth sores or large, fluid-filled blisters that often appear on the abdomen, arms, legs, groin, armpits. It is typically treated with steroids (either topical or taken as a pill) and with ointments that can help ease itching.

The researchers also found that in patients who developed bullous pemphigoid, their cancers tended to be more likely to respond to immunotherapy. Interestingly, this is not the first time that a skin-related side effect was found to potentially be indicative of a strong immunotherapy response. However, since bullous pemphigoid can become severe and result in dose limitation — or even discontinuation of treatment — it is important that the condition is caught and treated quickly.

“We recommend that patients aged 70 years and older and those being treated for melanoma or (non-melanoma skin cancer) be counseled about the risk for (bullous pemphigoid) before (immune checkpoint inhibitors) initiation,” the authors wrote. “In addition, given the association of (immune checkpoint inhibitor)-induced (bullous pemphigoid) with improved initial and overall tumor response, early identification of this toxic effect is important in patients who initially respond to (immune checkpoint inhibitors) and develop pruritic, eczematous, urticarial, erosive, or vesiculobullous eruptions, (immune checkpoint inhibitor)-induced (bullous pemphigoid) should be considered.”

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