Cutaneous immune‐related adverse events from immune checkpoint inhibitor therapy: Moving beyond “maculopapular rash”

Abstract

SummaryUncoupling toxicity from therapeutic effect lies at the foundation of the current state of the field of cutaneous immune‐related adverse events to immune checkpoint inhibitor therapy. This will be achieved through understanding the drivers of toxicity, tumor response, and resistance via large, well‐powered population‐level studies, institutional cohort data, and cellular‐level data. Increasing diagnostic specificity through the application of consensus disease definitions has the power to improve clinical care and each approach to research. Cutaneous immune‐related adverse events are associated with increased survival, and their treatment must invoke the maintenance of a delicate balance between immunosuppression, anti‐tumor effect of immune checkpoint inhibitor therapy, and quality of life. The multidisciplinary care of cancer patients with adverse events is critical to optimizing clinical and translational research outcomes and, as such, dermatologists are vital to moving the study of cutaneous adverse events forward.

Radiation Dermatitis: Radiation-Induced Effects on the Structural and Immunological Barrier Function of the Epidermis

“…Precision radiotherapy has improved the therapeutic efficacy of cancer treatment, either alone or in combination with other treatment modalities, such as immunomodulatory drugs. Immune checkpoint inhibitors have revolutionized cancer treatment in recent years and offer new opportunities to treat a variety of tumors [ 4 ], but they also pose a risk of dermatological side effects [ 5 ]. Currently, the impact of combining immune checkpoint inhibitors with radiotherapy on normal or tumor tissue reactions is not fully understood, especially whether it may lead to an increased incidence of dermatologic adverse events [ 6 ].…”

Improved Dermatologist, Patient, and Oncologist Collaboration Needed During Cancer Drug Development

“…The spectrum of DAEs that can develop during systemic chemotherapy is broad and, like treatment of other dermatologic conditions, the specificity of morphology and dermatologic diagnosis is important for consistent assessment across clinical trials and to form optimal approaches to management of DAEs caused by systemic chemotherapy . The use of nondiagnostic and unspecific dermatologic terms when reporting DAEs related to systemic chemotherapy can lead to inconsistent, nonspecific, and less effective management, and the findings by Shaigany et al that nearly one-third of DAE reporting in systemic cancer treatment clinical trials use nonspecific dermatology terminology signals an ongoing need for improvement of the dermatologic precision of DAE reporting during cancer clinical trials …”

“…Collaboration between dermatologists and oncologists through the Multinational Association of Supportive Care in Cancer (MASCC) Skin Toxicity Study similarly improved dermatologic specificity in DAE assessment and the collaborative changes were ultimately used in a revision of the most commonly used adverse reaction assessment tool used in clinical trials—the Common Terminology Criteria for Adverse Events—to add specificity to numerous skin related adverse events (for example, the DAE nail changes was updated to 3 unique and separate nail toxicities: discoloration, nail ridging, and nail loss, to reflect that each unique nail DAE has different impact and risk to patients) . Specificity of DAE reporting is also important during treatment with immune checkpoint inhibitors for cancer, where 29.3% of dermatologic immune-related adverse events are refractory to systemic steroids and where the most effective assessment and management of immune checkpoint inhibitor–related DAEs also relies on accurate and specific skin morphology, as well as histopathologic interpretation and clinicopathologic correlation . Ongoing collaborative work between dermatologists and oncologists, including increased representation of dermatologic expertise, particularly in early stages of drug development such as in cancer clinical trials, to increase diagnostic specificity in DAE reporting, will be important to improve more timely and accurate monitoring and management of systemic chemotherapy-related DAEs.…”

The evolving landscape of immune‐related adverse events that follow immune checkpoint immunotherapy in cancer patients

“…34 While most of these cutaneous immune-related adverse effects (cirAEs) are mild, severe presentations occur. 35 Fiamma Berner and Lukas Flatz focused their review on two emerging classes of self-antigens involved in skin toxicity and pneumonitis in non-small cell lung cancer patients undergoing ICI therapy. 36 They discuss how these self-antigen-specific T cells are believed to play a dual role by mediating irAE to skin and lung, and by promoting anti-tumor immune responses.…”