Survival improved among immune checkpoint inhibitor recipients with cirAEs
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Cutaneous immune-related adverse events are associated with increased survival rates among immune checkpoint inhibitor recipients, particularly in patients with melanoma, according to a study.
“Immune checkpoint blockade has become the standard of care for a growing number of advanced cancers,” Yevgeniy R. Semenov, MD, MA, of the department of dermatology at Massachusetts General Hospital and Harvard Medical School, told Healio.
“Cutaneous immune-related adverse events (cirAEs) are the most common and often the earliest toxicities to occur in the setting of immunotherapy,” Semenov continued, “but robust data on the prognostic role of these toxicities is largely limited, due to predominance of either single institutional cohorts with limited generalizability or clinical trial data with limited dermatology phenotyping in previous literature.”
Semenov noted that this study is a follow-up on a previously published manuscript, which leverages population-level claims data to investigate the survival implications of cutaneous toxicities in the setting of immune checkpoint inhibitor (ICI) therapy. However, claims data does not enable granular phenotyping of immunotherapy toxicities, which typically requires chart level information extracted from the electronic health records and manual expert review of the events to ascertain likelihood of a cirAE.
In the current study, Semenov, along with first study co-authors Shijia Wang, MBI, Kimberly Tang, BA, and Guihong Wan, PhD, second study author Nga Nguyen, MD, MPH, and colleagues, examined the mortality of ICI patients with cirAE manifestations, taking into account morphology-specific implications.
A large-scale, multi-institutional clinical registry with manual cirAE phenotyping was used to compile patient charts of 3,731 ICI recipients.
Whereas previous clinical trial reports found cirAEs to occur in 40% of ICI recipients, the current study results showed that 18.1% of the included 3,731 ICI recipients developed cirAEs. Furthermore, those who developed cirAEs demonstrated decreased mortality rates (HR = 0.87; 95% CI, 0.79-0.98), with the most significant decrease being 33% among melanoma patients (HR = 0.67; P = .003).
“This risk reduction is particularly accentuated among patients who developed several types of cirAEs — lichenoid drug eruption (49% risk reduction in mortality), psoriasiform dermatitis (48% risk reduction in mortality), vitiligo (71% risk reduction in mortality), itch without rash (29% risk reduction in mortality), acneiform eruption (66% risk reduction in mortality), and nonspecific rash (32% risk reduction in mortality), demonstrating that the type of rash also plays an important role in prognosticating immunotherapy response,” Semenov said.
Overall, the authors found that cirAE development is associated with a 13% decrease in mortality, and that patients who develop cirAEs live on average 10.5 months longer than those that do not.
The retrospective design and single geographic location were limitations to this study, according to the researchers.
“The overall implication of this large multi-institutional study independently validated our previous findings about the important prognostic role of cutaneous toxicities from immunotherapy, demonstrating that while these events are a potential source of discomfort to ICI recipients, they are not without an important silver lining,” Semenov said.
“Appropriate and timely recognition of cirAEs and their individual morphologies can provide important prognostic insights into the patient’s overall response to immunotherapy and serve as an early biomarker of therapeutic efficacy in this setting,” Semenov concluded.
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