When Cancer Therapy Affects the Skin: A Guide for Clinicians

Nearly every medication comes with side effects, and in cancer therapies, they can be severe. Clinicians must often weigh the benefits of treatment against potential adverse effects. At the 29th Training Week for Practical Dermatology and Venerology in Munich, Germany, specialists explored the manifestations of cutaneous drug reactions and how to manage them.

Immune-Mediated Dermatologic Side Effects

In addition to chemotherapy, there are three other pillars of pharmacologic cancer therapy, as outlined by the first speaker, Mirjana Ziemer, MD, PhD, senior physician and dermatologist at University Hospital Leipzig, Leipzig, Germany:

• Targeted therapies: Including B-Raf serine-threonine kinase, mitogen-activated protein kinase kinase, Hedgehog, and mammalian target of rapamycin inhibitors.
• Monoclonal antibodies: Especially immuno-agonistic types.
• Other immunotherapeutics: Cytokines, chemo-immunoconjugates, oncolytic viruses, and microRNA.

One example in this third group is thalidomide, an immunomodulatory drug used to treat multiple myeloma, Langerhans cell histiocytosis, and mycosis fungoides. Although known for its teratogenic effects, thalidomide can also trigger strong skin reactions, such as maculopapular rashes, pruritus, vitiligo, and potentially life-threatening epidermal necrolysis, including Stevens-Johnson syndrome.

Combination Therapies

Studies show that combining the checkpoint inhibitors nivolumab and ipilimumab induces cutaneous side effects in around 60% of patients. Of those on monotherapy, nearly 50% still experience skin reactions. Common side effects include lichen planus–like reactions, psoriasis, and rashes with eosinophilia and systemic symptoms, often referred to in English under the general term “skin rash”; a more precise term is required in German to ensure proper diagnosis.

Ziemer noted that patients with lichenoid drug–induced rashes require comprehensive skin examinations, as these reactions can involve balanitis, vulvitis, and oral mucositis, often leading to treatment discontinuation.

Epidermal Necrolysis: A Potentially Fatal Complication

Although rare, severe exanthematous drug reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) are possible. Initial signs resemble erythema multiforme, which emerges rapidly after a new drug is administered. In cases of TEN, unlike erythema exudativum multiforme, lesions merge. Histologically, both conditions are associated with keratinocyte necrosis at the epidermal junction, though TEN is cytotoxic in origin. With a 30%-40% mortality rate, TEN requires urgent treatment and referral to a specialized burn unit.

Steroid-Resistant Reactions

Carolin Ertl, MD, dermatology resident at Ludwig-Maximilians-Universität München, Munich, Germany, reported on rare, severe, and therapy-resistant side effects of checkpoint inhibitors. Common cutaneous side effects such as dermatitis, as well as rare conditions such as pneumonitis or myocarditis, can arise. Immune-mediated reactions can become steroid-dependent or resistant, requiring a swift transition to a second-line treatment such as the tumor necrosis factor alpha inhibitor infliximab. While effective, infliximab can negatively affect tumor response.

To enhance management of immune-mediated side effects, Ertl recommended using online registries such as Side Effect Registry Immuno-Oncology. Systematic documentation of side effects helps to identify risk factors, pathogenesis, and effective treatments.

Tebentafusp: High-Efficacy, Significant Side Effects

Christoffer Gebhardt, MD, professor of dermatooncology at University Medical Center Hamburg-Eppendorf in Hamburg, Germany, highlighted side-effect management for two novel oncologic drugs. Tebentafusp, approved in 2022 for uveal melanoma, links T cells to the tumor antigen gp100 to facilitate tumor cell destruction, but it only works in patients who have the HLA-A*0201 genotype. Close to 90% of patients experience cytokine release syndrome after the first dose; it is less common in later doses but often more severe. Tebentafusp also acts on melanocytes, causing dermatologic side effects such as pruritus, cutaneous edema, and rash in around 90% of cases, which are typically responsive to steroids.

Tebentafusp is generally suitable for patients with metastatic uveal melanoma, especially those with low tumor burden and specific human leukocyte antigen genotypes. Monitoring circulating tumor DNA can help to assess the balance between therapeutic benefit and side effects.

Mogamulizumab: Key Second-Line Therapy

Approved in 2018, mogamulizumab is a second-line treatment for cutaneous T-cell lymphoma (Sézary syndrome) and mycosis fungoides. Side effects often manifest as drug rashes, lymphocytopenia, gastrointestinal symptoms, and fatigue. Depending on severity, dose adjustments or prolonged, lower-dose therapy may be needed.

A common side effect is mogamulizumab-associated rash (MAR), presenting as lichenoid dermatitis and plaques. Although treatment discontinuation can occur, patients with MAR often respond better to the drug. MAR resembles mycosis fungoides, so a biopsy is necessary for an accurate diagnosis.

No Two Side Effects Are Same

Drug-based tumor treatments can result in therapy-resistant, dangerous side effects, either common or rare, requiring tailored diagnosis and treatment. Dosages and active ingredient combinations must be customized for each patient and their side effects. Frequent biopsies and thorough checks of all skin and mucosal areas are crucial to avoid missing a potentially life-threatening case of TEN.

This story was translated from Coliquio using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.