Women at higher risk for dermatologic side effects during immunotherapy

A retrospective cohort study has shown an association between female sex and the risk for dermatologic adverse events due to checkpoint inhibition. This risk was approximately twice as high as the risk for males.

Targeted therapy with immune checkpoint inhibitors (ICI) has become an important treatment in many forms of advanced cancer [1–3]. It is known that, despite ICI therapy not only being effective but also safe, immune-related adverse events (irAE) appear regularly. “Dermatologic adverse events (dAE) are the most common set of irAE and occur in 30–50% of patients on ICI monotherapy,” said Mr Jordan T. Said (Harvard School of Medicine, MA, USA). These dAE may present as psoriasiform dermatitis, lichenoid reactions, vitiligo, and bullous pemphigoid. In severe cases, steroid use or even discontinuation of ICI therapy may be necessary.

Until now, evidence was limited on potential risk factors for the development of irAE or dAE. However, as previous study results identified a greater risk for irAE in pre- compared with post-menopausal women on ICI, the current retrospective single-centre cohort study strove to further evaluate the impact of sex on the development of dAE in patients with metastatic melanoma that received ICI treatment between 2011 and 2016. The study included 142 men with a mean age of 65 years and 93 women with a mean age of 60 years. Among the females, 27 had a pre- and 66 a post-menopausal status. In 62.4% of the women and 48.6% of the men, ICI-associated dAE were confirmed.

A multivariate logistic regression identified that women had a >2-fold likelihood to suffer from dAE compared with men (OR 2.11; 95% CI 1.17–3.82; P=0.01). When differentiating by hormonal status, results were only significant in the post-menopausal group. However, the secondary analysis detected that the OR for the pre- versus post-menopausal groups was numerically similar (OR 1.97; 95% CI 0.56–6.67; P=0.4 vs OR 2.17; 95% CI 1.00–4.69; P=0.05). This led the authors to assume that factors beyond sex hormones might have an influence. Mr Said concluded that the findings of the study may guide clinicians when counselling women about the risk of dAE entailed by ICI.

1. Bui AN, et al. Female sex is associated with higher rates of dermatologic adverse events among patients with melanoma receiving immune checkpoint inhibitor therapy: a retrospective cohort study. Session S033, AAD VMX 2021, 23-25 April.
2. Wang E, et al. Ann Allergy Asthma Immunol. 2021:S1081-1206(21)00127-7.
3. Tattersall IW, et al. Yale J Biol Med. 2020;93(1):123-132.

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Posted on 7 June 20217 June 2021