Skin Toxicity May Predict Immune Checkpoint Inhibitor Response

By Marilynn Larkin

January 21, 2022

NEW YORK (Reuters Health) - In cancer patients, cutaneous immune-related adverse events (cirAEs) were strongly associated with response to immune checkpoint inhibitors (ICIs) and survival in a retrospective study.

"We used data from the U.S. and Europe to identify an approximately 20% reduction in mortality among patients who developed skin toxicities compared to those who did not," Dr. Yevgeniy Semenov of Massachusetts General Hospital, Harvard Medical School in Boston told Reuters Health by email. "What was surprising is that we also saw that different types of rashes had different degrees of protection, with vitiligo, lichenoid eruptions, and psoriasiform eruptions having among the greatest survival benefits (by as much as 50%)."

As reported in JAMA Dermatology, Dr. Semenov and colleagues assessed the association between developing cirAEs following anti-programmed cell death 1 (PD-1) or anti-programmed cell death ligand 1 (PD-L1) therapy and patient survival.

A total of 7,008 patients (mean age, 68.2; 43.3% women) and matched controls were included in the analysis. All patients developed cirAEs after anti-PD-1 or anti-PD-L1 therapy for malignant neoplasms of digestive organs, bronchus or lung, melanoma of skin, and urinary tract.

The following cirAEs were associated with significant protection of mortality: pruritus (hazard ratio, 0.695), drug eruption (HR, 0.755); xerosis (HR, 0.626); nonspecific rashes (HR, 0.704); and appearance of any cirAE (HR, 0.778).

Psoriasis (HR, 0.703) and lichen planus/lichenoid dermatitis (HR, 0.511) were associated with significant protective clinical effects.

The following were associated with "strong" effects: eczematous dermatitis (HR, 0.612); vitiligo (HR, 0.534); bullous pemphigoid (HR, 0.524); and Grover disease (HR, 0.468).

The authors note, "The lack of achieved statistical significance among some dermatoses is likely because of the insufficient sample size of rarer diagnoses and few observed deaths in these subgroups during the study follow-up."

Dr. Semenov said, "Our next steps are to understand specific biological mechanisms that may explain the relationship between these skin reactions and a patient's prognosis and whether interventions used to treat or prevent them may impact survival."

"The idea of tissue homing, where systemically activated memory T-cells are directed to their specific tissue, suggests that the tissue source of the tumor may be an important variable in the generation of immune-related toxicities," he noted.

"We believe the differential prognostic survival implications...are also related to the degree of cytotoxicity present in the type of skin eruption, with more cytotoxic eruptions likely signaling a greater anti-tumor response from immunotherapy," he said. "For example, some types of skin eruptions are more characteristically cytotoxic in nature (e.g., vitiligo, lichen planus) than other skin inflammatory morphologies."

"Since skin toxicities tend to occur early in the course of immunotherapy, our findings also present an opportunity to identify patients who are more likely to benefit from their current immunotherapy regimen versus those who may need to be considered for a stronger or alternative treatment regimen," Dr. Semenov concluded.

Dr. Adam Friedman, Professor and Chair of Dermatology at George Washington School of Medicine and Health Sciences in Washington DC, commented on the study in an email to Reuters Health. "These previous studies that also found a positive correlation between cutaneous adverse events, in this case to immunotherapy, and a positive treatment impact."

"While these visual cues of treatment success often lead the medical team to celebrate, data have shown that the impact of these adverse events on the patient are tremendous, often more concerning to them than the malignancy itself," he noted.

"The field of supportive oncodermatology emerged to enable patients to have their cake and eat it too, meaning capitalize on the incredible new armamentarium of targeted therapies without suffering through the expected cutaneous adverse events," he added. "The goal to is keep patients on therapy with preventive and mitigation strategies, rather than hold or withdraw therapy, which may or may not impede treatment outcomes."

SOURCE: JAMA Dermatology, online January 12, 2022.