Defining D-irAEs: consensus-based disease definitions for the diagnosis of dermatologic adverse events from immune checkpoint inhibitor therapy

Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(4), P. e007675 - e007675

Published: April 1, 2024

With an increasing number of patients eligible for immune checkpoint inhibitors, the incidence immune-related adverse events (irAEs) is on rise. Dermatologic (D-irAEs) are most common and earliest to manifest, often with important downstream consequences patient. Current guidelines lack clarity in terms diagnostic criteria D-irAEs. The goal this project better define D-irAE purposes identification, diagnosis, future study group diseases.The objectives were develop consensus guidance approach D-irAEs including disease definitions severity grading. Knowing that among oncologists, dermatologists, irAE subspecialists would be critical usability, we formed a Disease Definition Panel. panel was composed 34 experts, rheumatologist, allergist/immunologist from 22 institutions across USA internationally. A modified Delphi process used, two rounds anonymous ratings by panelists virtual meetings discuss areas controversy. Panelists rated content appropriateness, accuracy 9-point scales electronic surveys provided free text comments. working aggregated survey responses incorporated them into revised definitions. Consensus based numeric using RAND/UCLA Appropriateness Method prespecified definitions.Following revisions panelist feedback, all items received second round ratings. achieved 10 core diagnoses: ICI-vitiligo, ICI-lichen planus, ICI-psoriasis, ICI-exanthem, ICI-bullous pemphigoid, ICI-Grover's, ICI-eczematous, ICI-eruptive atypical squamous proliferation, ICI-pruritus without rash, ICI-erosive mucocutaneous. standard evaluation also found reach consensus, disease-specific exceptions detailed when necessary. Each disorder's description includes further details subtypes, symptoms, supportive exam findings, three levels certainty (definite, probable, possible).These consensus-driven standardize classification useable framework multiple disciplines will foundation work. Given their usability representative group, anticipate they can used broadly clinical research settings.

Language: Английский

Risk Factors Analysis of Cutaneous Adverse Drug Reactions Caused by Targeted Therapy and Immunotherapy Drugs for Oncology and Establishment of a Prediction Model

Clinical and Translational Science, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 1, 2025

Targeted therapy and immunotherapy drugs for oncology have greater efficacy tolerability than cytotoxic chemotherapeutic drugs. However, the cutaneous adverse drug reactions associated with these newer therapies are more common remain poorly predicted. An effective prediction model is urgently needed essential. This retrospective study included 1052 patients, divided into train set, test external validation set. As a data-driven study, total of 76 variables were collected. Univariate logistic analysis, least absolute shrinkage selection operator regression, stepwise regression utilized feature screening. Finally, nine machine-learning models constructed compared, grid search was performed to adjust parameters. Model performance evaluated using calibration curve area under receiver operating characteristic (AUROC). Nine risk factors eventually identified: age, treatment modality, cancer types, history allergies, age-corrected Charlson comorbidity index, percentage eosinophils, number monocytes, Eastern Cooperative Oncology Group Performance Status, C-reactive protein. Among models, best, demonstrating strong in set (AUROC = 0.734) 0.817). identified significant developed nomogram model. These findings important implications optimizing therapeutic maintaining quality life patients from perspective managing reactions. Trial Registration: ChiCTR2400088422.

Language: Английский

Safety of immune checkpoint inhibitors: An updated comprehensive disproportionality analysis and meta-analysis

Critical Reviews in Oncology/Hematology, Journal Year: 2024, Volume and Issue: 200, P. 104398 - 104398

Published: May 27, 2024

Language: Английский

Cancer type and histology influence cutaneous immunotherapy toxicities: a multi-institutional cohort study

British Journal of Dermatology, Journal Year: 2024, Volume and Issue: 191(1), P. 117 - 124

Published: Feb. 15, 2024

Abstract Background Cutaneous immune-related adverse events (cirAEs) are the most common toxicities to occur in setting of immune checkpoint inhibitor (ICI) therapy. Identifying patients who at increased risk developing cirAEs may improve quality life and outcomes. Objectives To investigate influence cancer type histology on development ICI therapy survival Methods This retrospective cohort study included recruited between 1 December 2011 30 October 2020. They received from 2020 with follow-up outcomes through 2021. We identified 3668 recipients were seen Massachusetts General Brigham Dana-Farber. Of these, 669 developed cirAEs. Records that incomplete or categories insufficient sample size excluded cohort. Multivariate Cox proportional hazards models used impact organ system cirAE development, after adjusting for demographics, Charlson Comorbidity Index, type, stage initiation, year initiation. Time-varying modelling was examine mortality. Results Compared other nonepithelial cancers (neuroendocrine, leukaemia, lymphoma, myeloma, sarcoma central nervous malignancies), cutaneous squamous cell carcinoma [cSCC; hazard ratio (HR) 3.57, P < 0.001], melanoma (HR 2.09, 0.001), head neck adenocarcinoma 2.13, = 0.009), genitourinary transitional 2.15, 0.001) 1.53, 0.037) significantly higher multivariate analyses. The translated into an adjusted benefit 0.37, cSCC 0.51, 0.011). Conclusions highest rate subsequent benefits observed malignancies treated therapies. improves our understanding would, therefore, appropriate counselling closer monitoring by their oncologists dermatologists throughout Limitations include its nature one geography.

Language: Английский

Severe cutaneous adverse reactions associated with the immune checkpoint inhibitors: A case/non‐case analysis using the Food and Drug Administration Adverse Event Reporting System

Australasian Journal of Dermatology, Journal Year: 2024, Volume and Issue: 65(3), P. 243 - 253

Published: April 4, 2024

The immune checkpoint inhibitors (ICIs) have been increasingly associated with severe cutaneous adverse reactions (SCARs). These reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction eosinophilia and systemic symptoms (DRESS) acute generalized exanthematous pustulosis (AGEP) are uncommon but potentially lethal. Despite the severity of these growing association ICIs, their specific risk mortality rates largely unexplored.

Language: Английский

Immune checkpoint inhibitor-induced dyshidrotic eczema following tremelimumab therapy for hepatocellular carcinoma

JAAD Case Reports, Journal Year: 2025, Volume and Issue: 58, P. 118 - 120

Published: Jan. 16, 2025

Language: Английский

Characterizing immune checkpoint inhibitor-related cutaneous adverse reactions: A comprehensive analysis of FDA adverse event reporting system (FAERS) database

Heliyon, Journal Year: 2024, Volume and Issue: 10(13), P. e33765 - e33765

Published: July 1, 2024

BackgroundThe increasing adoption of immune checkpoint inhibitors (ICIs) in clinical settings highlights their efficacy treating diverse conditions, while also emphasizing the potential for common cutaneous adverse reactions to arise. The aim this study is investigate a multitude impacting factors and determinants among patients presenting with ICI-associated reactions.MethodsWe conducted comprehensive analysis using data from FAERS. Our spans January 1, 2015, March 31, 2023, focusing on ICIs, including anti-PD-1, anti-PD-L1, anti-CTLA-4 agents.FindingsAmong 334,293 reported irAR, 17,431 were identified as (ARs). Predominant ARs included rash (21.01 %), pruritus (11.22 pemphigoid (3.90 %). Stevens-Johnson syndrome emerged most severe reaction (SCAR) (2.08 Anti-CTLA-4 agents exhibited higher toxicity compared anti-PD-1 anti-PD-L1 agents. Anti-PD-1 demonstrated an elevated mortality rate. combined use ICIs chemotherapy amplified risk SCAR mortality. Targeted therapy was factor but associated reduced median onset day 21 days, SCAR, it 23 days. Weight age predictors toxicity, Skin cancer increased skin lung heightened formation. number administered positively correlated mortality.InterpretationThis significance early identification effective management toxicities, along personalized follow-up care, essential strategies minimizing risks preventing treatment disruptions.

Language: Английский

Updates in toxicities associated with immune checkpoint inhibitors

Expert Review of Clinical Immunology, Journal Year: 2023, Volume and Issue: 19(9), P. 1117 - 1129

Published: June 5, 2023

Introduction Immune checkpoint inhibitors (ICIs) have become a pillar of treatment for numerous cancers with increasing use in combination other ICIs and earlier stages disease treatment. Although effective, ICI is accompanied by milieu potentially bothersome or even life-threatening toxicities known as immune-related adverse events (irAEs), necessitating careful monitoring early intervention.Areas covered In this review, we provide an overview recent advances surrounding toxicity pathophysiology the context relevant organ systems. An emphasis on current treatments toxicity, well updates steroid-refractory toxicities, chronic biomarkers will be focus update understanding irAEs.Expert opinion are major limitation deployment multi-agent regimens thus priority to understand, treat, prevent. Recent developments led greater these events, which may lead improved prevention mitigation strategies. Further, studies also suggested steroid-sparing approaches that useful. Ultimately, preventing managing irAEs key goal toward successful across broader range patients cancer.

Language: Английский

Selected cutaneous adverse events in patients treated with ICI monotherapy and combination therapy: a retrospective pharmacovigilance study and meta-analysis

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: June 2, 2023

Introduction: Cutaneous adverse events are commonly reported immune-related (irAEs), some of which serious or even life-threatening, and it is essential to study these specific cutaneous AEs understand their characteristics risk. Methods: We performed a meta-analysis published clinical trials for immune checkpoint inhibitors (ICIs) evaluate the incidence events, using data from PubMed, Embase, Cochrane Library databases. Results: A total 232 with 45,472 patients were involved. Results showed that anti-PD-1 targeted therapy combinations associated higher risk most selected events. In addition, retrospective pharmacovigilance was conducted Food Drug Administration (FDA) Adverse Events System database. Reporting odds ratio (ROR) Bayesian information components (IC) used perform disproportionality analysis. Cases extracted January 2011 September 2020. identified 381 (20.24%) maculopapular rash, 213 (11.32%) vitiligo, 215 (11.42%) Stevens-Johnson syndrome (SJS), 165 (8.77%) toxic epidermal necrolysis (TEN) cases. For anti-PD-1/L1 combined anti-CTLA-4 strongest signal (ROR: 55.89; 95% CI: 42.34-73.78; IC025: 4.73). Palmar-plantar erythrodysesthesia (PPE) significant association VEGF (R)-TKIs 18.67; 14.77-23.60; 3.67). SJS/TEN, antiPD-1 3.07; 2.68-3.52; 1.39). The median onset time vitiligo SJS/TEN 83 24 days, respectively. Conclusion: Overall, in AEs, each them characteristics. It necessary realize differences take appropriate interventions different regimens.

Language: Английский

Increased risk of cutaneous immune-related adverse events in patients treated with talimogene laherparepvec and immune checkpoint inhibitors: A multi-hospital cohort study

Journal of the American Academy of Dermatology, Journal Year: 2023, Volume and Issue: 88(6), P. 1265 - 1270

Published: March 21, 2023

Language: Английский