Histologic subtype of cutaneous immune-related adverse events predicts overall survival in patients receiving immune checkpoint inhibitors

Hirotsu, Kelsey E.; Scott, Madeleine; Márquez, César; Tran, Anhthy T; Rieger, Kerri E.; Novoa, Roberto A.; Robinson, William H.; Kwong, Bernice Y.; Zaba, Lisa C.

doi:10.1016/j.jaad.2021.11.050

Cited by 10 publications

(9 citation statements)

References 6 publications

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“…Cutaneous irAEs are often the first type of immunerelated toxicity in patients on ICI therapy and may be predictive of future extracutaneous irAEs. 21,81 Thus, patients who develop a cutaneous irAE need close monitoring for signs or symptoms of extracutaneous irAEs including myocarditis, pneumonitis, colitis and endocrinopathies. Patients receiving ICI therapy, even for cancers other than melanoma, can also develop new malignant skin lesions that may potentially mimic cutaneous irAEs.…”

Section: Implications Of Cutaneous Immune-related Adverse Eventsmentioning

confidence: 99%

“…83 Mild cutaneous irAEs usually do not necessitate any disruptions to ICI therapy, whereas moderate and severe reactions may necessitate interruption and/or discontinuation, which can significantly worsen clinical outcomes and even increase mortality. 81 Furthermore, moderate and severe cutaneous irAEs may require treatment with immunosuppressants such as systemic corticosteroids, 84,85 which could, theoretically, negate the increased immune system activation brought on by ICIs, leading to poorer clinical outcomes. However, mixed evidence exists as to whether the use of systemic corticosteroids decreases the effectiveness of ICIs.…”

Section: Implications Of Cutaneous Immune-related Adverse Eventsmentioning

confidence: 99%

“…51 Additionally, the specific histological subtype of a cutaneous irAE may have prognostic value, as the lichenoid or spongiotic subtypes are associated with better clinical outcomes whereas the superficial perivascular dermatitis or vacuolar subtypes were associated with worse clinical outcomes. 81 Additional mechanistic studies are necessary to further characterize the scope of pathways involved in cutaneous irAEs and to identify rational pathways that may be differentially targeted using specific agents that should not affect anti-tumour response. As examples, psoriasiform irAEs have been treated with anti-IL17 and anti-IL-23 agents, which did not affect antitumour response, 54,90 while eczematous dermatitis has been treated with dupilumab 91 and pruritus with anti-IgE treatment 92 (Table 3).…”

Section: Implications Of Cutaneous Immune-related Adverse Eventsmentioning

confidence: 99%

“…Cutaneous irAEs are often the first type of immune‐related toxicity in patients on ICI therapy and may be predictive of future extracutaneous irAEs 21,81 . Thus, patients who develop a cutaneous irAE need close monitoring for signs or symptoms of extracutaneous irAEs including myocarditis, pneumonitis, colitis and endocrinopathies.…”

Section: Implications Of Cutaneous Immune‐related Adverse Eventsmentioning

confidence: 99%

“…The development of guttate or extensive (> 10% BSA) psoriasiform irAEs has also been associated with improved clinical outcomes 51 . Additionally, the specific histological subtype of a cutaneous irAE may have prognostic value, as the lichenoid or spongiotic subtypes are associated with better clinical outcomes whereas the superficial perivascular dermatitis or vacuolar subtypes were associated with worse clinical outcomes 81 …”

Section: Implications Of Cutaneous Immune‐related Adverse Eventsmentioning

confidence: 99%

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Mechanisms of dermatological toxicities to immune checkpoint inhibitor cancer therapies

Seervai

Sinha

Kulkarni

2022

Clinical and Experimental Dermatology

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The discovery of immune checkpoint inhibition (ICI) sparked a revolution in the era of targeted anticancer therapy. However, although monoclonal antibodies targeting the cytotoxic T-lymphocyte antigen-4 and programmed death-1 axes have improved survival in patients with advanced cancers, these immunotherapies are associated with a wide spectrum of dermatological immune-related adverse events (irAEs), ranging from mild to life-threatening. Several publications have addressed the clinical and histopathological classification of these skin-directed irAEs, their impact on anti-tumour immunity and survival, and the critical role of supportive oncological dermatology in their management. In this paper, we review the current understanding of the mechanistic drivers of immune-related skin toxicities with a focus on inflammatory, immunobullous and melanocyte/pigment-related reactions. We detail the specific immune-based mechanisms that may underlie different cutaneous reactions. We also discuss potential mechanisms as they relate to extracutaneous irAEs and the lessons learned from these, the potential overlap with cutaneous irAEs, techniques to study differences in immune-related vs. de novo skin reactions, and how treatment of these AEs impacts cancer treatment, patient quality of life and overall survival. An improved understanding of the mechanistic basis of cutaneous irAEs will allow clinicians to develop and use blood-based biomarkers that could help ultimately predict onset and/or severity of these irAEs, and to implement rational mechanistic-based treatment strategies that are targeted to the irAEs while potentially avoiding reducing the anti-tumour effect of ICIs.

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Section: Implications Of Cutaneous Immune-related Adverse Eventsmentioning

confidence: 99%

Section: Implications Of Cutaneous Immune-related Adverse Eventsmentioning

confidence: 99%

Section: Implications Of Cutaneous Immune-related Adverse Eventsmentioning

confidence: 99%

Section: Implications Of Cutaneous Immune‐related Adverse Eventsmentioning

confidence: 99%

Section: Implications Of Cutaneous Immune‐related Adverse Eventsmentioning

confidence: 99%

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Mechanisms of dermatological toxicities to immune checkpoint inhibitor cancer therapies

Seervai

Sinha

Kulkarni

2022

Clinical and Experimental Dermatology

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Cutaneous Adverse Events and Cancer Survival Prognosis With Immune Checkpoint Inhibitor Treatment

Du,

Wu,

Chen

et al. 2023

JAMA Dermatol

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ImportanceGrowing research suggests that the prevalence of cutaneous immune-related adverse events (cirAEs) is associated with favorable outcomes among individuals with cancer who receive immune checkpoint inhibitor (ICI) treatment.ObjectiveTo identify whether the presence of cirAEs and their subtypes subsequent to ICI administration is associated with enhanced cancer prognosis.Data SourcesThe PubMed, Embase, Cochrane Library, and Web of Science databases were searched for publications examining the association between cirAE development during ICI treatment and subsequent cancer prognosis. The initial search was limited to English-language publications from database inception until December 31, 2022; a subsequent search was performed on May 21, 2023.Study SelectionTwo reviewers independently scrutinized the identical articles and included those that constituted original research evaluating the association between cirAE development and cancer prognosis.Data Extraction and SynthesisThe search terms, study objectives, and methodological protocols were defined before study initiation. The aforementioned 2 reviewers performed data extraction independently and resolved discrepancies through agreement. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis and the Meta-analysis of Observational Studies in Epidemiology reporting guidelines. The protocol was prospectively registered with PROSPERO. Data analyses were conducted between May 21 and June 1, 2023.Main Outcomes and MeasuresThe major outcome end points were overall survival (OS) and progression-free survival (PFS). Subgroup analyses were also conducted according to cirAE type, cancer type, geographic region, study design, and ICI type. Given the heterogeneity inherent in the included studies, a DerSimonian-Laird random-effects model was adopted.ResultsThis systematic review and meta-analysis included 23 studies with a total of 22 749 patients treated with ICIs. The occurrence of cirAEs was associated with improved OS (hazard ratio [HR], 0.61 [95% CI, 0.52-0.72]; P &lt; .001) and PFS (HR, 0.52 [95% CI, 0.41-0.65]; P &lt; .001). Consistent results were observed across all subgroups stratified by study design, geographic region, ICI type, and cancer type, aligning with the overall estimate of OS and PFS improvement. However, no statistically significant differences were identified in terms of PFS within studies conducted in the US.Conclusions and RelevanceIn this systematic review and meta-analysis, the presence of cirAEs and their subtypes was associated with improved prognosis for individuals with cancer undergoing ICI treatment. These findings suggest that cirAEs may have useful prognostic value in ICI treatment.

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Evaluating patterns of co-occurrence between cutaneous and noncutaneous immune-related adverse events after immune checkpoint inhibitor therapy

Asdourian¹,

Shah²,

Jacoby³

et al. 2023

Journal of the American Academy of Dermatology

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Histologic subtype of cutaneous immune-related adverse events predicts overall survival in patients receiving immune checkpoint inhibitors

Cited by 10 publications

References 6 publications

Mechanisms of dermatological toxicities to immune checkpoint inhibitor cancer therapies

Mechanisms of dermatological toxicities to immune checkpoint inhibitor cancer therapies

Cutaneous Adverse Events and Cancer Survival Prognosis With Immune Checkpoint Inhibitor Treatment

Evaluating patterns of co-occurrence between cutaneous and noncutaneous immune-related adverse events after immune checkpoint inhibitor therapy

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