Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update

Journal of Clinical Oncology, Journal Year: 2021, Volume and Issue: 39(36), P. 4073 - 4126

Published: Nov. 1, 2021

To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events (irAEs) in patients treated with immune checkpoint inhibitor (ICPi) therapy.A multidisciplinary panel medical oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, neurology, hematology, emergency medicine, nursing, trialists, advocacy experts was convened to update guideline. Guideline development involved a systematic literature review an informal consensus process. The focused evidence published from 2017 through 2021.A total 175 studies met eligibility criteria were pertinent recommendations. Because paucity high-quality evidence, recommendations are based expert consensus.Recommendations for specific organ system-based toxicity diagnosis presented. While varies according system affected, general, ICPi therapy should be continued close monitoring grade 1 toxicities, except some neurologic, hematologic, cardiac toxicities. may suspended most 2 consideration resuming when symptoms revert ≤ 1. Corticosteroids administered. Grade 3 toxicities generally warrant suspension ICPis initiation high-dose corticosteroids. tapered over course at least 4-6 weeks. Some refractory cases require other immunosuppressive therapy. In permanent discontinuation is 4 endocrinopathies that have been controlled by hormone replacement. Additional information available www.asco.org/supportive-care-guidelines.

Language: Английский

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Adverse cutaneous toxicities by PD-1/PD-L1 immune checkpoint inhibitors: pathogenesis, treatment, and surveillance

Cutaneous and Ocular Toxicology, Journal Year: 2022, Volume and Issue: 41(1), P. 73 - 90

Published: Jan. 2, 2022

Introduction The therapeutic use of humanised monoclonal programmed cell death 1 (PD-1) (pembrolizumab, and nivolumab) ligand-1 (PD-L1) (atezolizumab, avelumab, durvalumab) immune checkpoint inhibitors (ICPi) as potent anticancer therapies is rapidly increasing. mechanism signalling anti-PD-1/PD-L1 involves triggering cytotoxic CD4+/CD8 + T activation subsequent abolition cancer cells which induces specific immunologic adverse events that are to these therapies. These drugs can cause numerous cutaneous reactions characterized the most frequent immune-related (irAEs). Majority irAEs range from non-specific eruptions detectible skin manifestations, may be self-limiting present acceptable toxicity profiles, while some produce life-threatening complications.Objective This review aims illuminate associated related used in oncology along with relevant mechanism(s) management.Areas covered Literature was searched using various databases including Pub-Med, Google Scholar, Medline. search mainly involved research articles, retrospective studies, case reports, clinicopathological findings. With this article, an overview therapy, well suggestions, have been provided, so their recognition at early stages could help better management would prevent treatment discontinuation.HIGHLIGHTSCutaneous effects prevalent induced by immune-checkpoint antibodies.Cutaneous toxicities manifest form maculopapular rash pruritus.More complications also occur, vitiligo, worsened psoriasis, lichenoid dermatitis, mucosal involvement (e.g. oral reaction), dermatomyositis, lupus erythematosus.Cutaneous manifestations Stevens-Johnson syndrome/toxic epidermal necrolysis (TEN).Dermatologic usually mild, readily manageable, rarely result significant morbidity.Adequate event lead prevention worsening lesions limit disruption.

Language: Английский

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Dermatologic Adverse Events of Systemic Anticancer Therapies: Cytotoxic Chemotherapy, Targeted Therapy, and Immunotherapy

American Society of Clinical Oncology Educational Book, Journal Year: 2020, Volume and Issue: 40, P. 485 - 500

Published: May 1, 2020

Over the past 2 decades, rapid advancement in systemic anticancer therapeutics has led to astounding improvement survival rates of patients with cancer. However, this celebrated progress brought it an evolving spectrum drug toxicities that limit their prodigious capabilities. Cutaneous adverse events are most frequent these toxicities, substantial impact on quality life and commonly resulting dose reduction or change therapy. Thus, familiarity array dermatologic manifestations caused by drugs is prudent for patient treatment. As such, advent dedicated oncodermatologists, introduction into multidisciplinary cancer care, been crucial optimizing treatment through therapeutic achievement overall well-being. This review will address epidemiology, clinical presentations, management strategies major agents, including cytotoxic chemotherapy, targeted therapy, immunotherapy.

Language: Английский

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Management of immune related adverse events induced by immune checkpoint inhibition

Cancer Letters, Journal Year: 2019, Volume and Issue: 456, P. 80 - 87

Published: April 30, 2019

Language: Английский

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Psoriasis and psoriasiform reactions secondary to immune checkpoint inhibitors

Dermatologic Therapy, Journal Year: 2021, Volume and Issue: 34(2)

Published: Feb. 4, 2021

The advent of Immune Checkpoint Inhibitors (ICIs) as a standard care for several cancers, including melanoma and head/neck squamous cell carcinoma has changed the therapeutic approach to these conditions, drawing at same time attention on some safety issues related their use. To assess incidence psoriasis specific immune-related cutaneous adverse event attributing ICIs using Eudravigilance reporting system. All reports drug reactions (ADRs) concerning either exacerbation or de novo onset psoriasis/psoriasiform associated use Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) inhibitors ipilimumab tremelimumab, Programmed Death protein 1/Programmed Death-Ligand 1 (PD-1/PD-L1) nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, cemiplimab were identified extracted from system, during period between date market licensing (for each study drug) 30 October 2020. 8213 ADRs with least one have been recorded, which 315 (3.8%) and/or psoriasiform ADR. In 70.8% patients had pre-existing disease. ICIs-related skin toxicity is well-established phenomenon, presenting sustained by an immune background based activity cells (CD4+/CD8+ T-cells, neutrophils, eosinophils, plasmocytes), inflammatory mediators, chemokines, tumor-specific antibodies. this setting, represents probably most paradigmatic model reactions, thus requiring adequate recognition no guidelines management are now available.

Language: Английский

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Treatment update for vitiligo based on autoimmune inhibition and melanocyte protection

Expert Opinion on Therapeutic Targets, Journal Year: 2023, Volume and Issue: 27(3), P. 189 - 206

Published: March 4, 2023

Introduction The treatment of vitiligo remains challenging due to the complexity its pathogenesis, influenced by genetic factors, oxidative stress and abnormal cell adhesion that collectively impact melanocyte survival trigger immune system attacks, resulting in death. Melanocytes are believed exhibit susceptibility defects cellular mechanisms, such as autophagy, reduce their ability resist stress, leading increased expression pro-inflammatory protein HSP70. low molecules, DDR1 E-cadherin, accelerates damage antigen exposure. Consequently, autoimmune attacks centered on IFN-γ-CXCR9/10-CXCR3-CD8+ T cells initiated, causing vitiligo.

Language: Английский

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Immune Checkpoint Inhibitor Toxicity in Head and Neck Cancer: From Identification to Management

Frontiers in Pharmacology, Journal Year: 2019, Volume and Issue: 10

Published: Oct. 23, 2019

Benefited from the continuously clarifying underlying biology of immune checkpoints and ligands-receptors interactions, emergence new anti-cancer treatment strategy -- immunotherapy has showed substantial benefits on several liquid solid tumors. Immune checkpoint inhibitors (ICIs) can block negative regulatory components enhance T-cell function, thus let to prominent activity. On account its promising effect various malignancies that in clinical trials, ICIs have been considered be most potent agents near future. Head neck cancer is 7th common neoplasm worldwide gross 5-year survival rate was only 60%. Managing locoregionally advanced, recurrent or metastatic head tumors were still challenging problems for both oncologists surgeons. Recent trials employing immune-modulating antibodies target cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) programmed cell death-1 (PD-1) herald a era therapy. However, like all other drugs, also side effects while upregulating system antitumor response, which known as immune-related adverse events (irAEs). Generally, irAEs transient, but sometimes they cause serious organ dysfunction, even fatal. In addition, due distinct anatomical feature, advanced often affect upper aerodigestive track dyspnea dysphagia. Toxicities may more lethal such patients. Thus, increasing application anti-checkpoint cancer, there urgent need ascertain safety this novel strategy. Here we compile review existing toxicity during treatment. The particular manifestation, characteristics complication development fatal cases management strategies discussed. This provide vital information future oncology practice.

Language: Английский

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Perspectives on Psoriasiform Adverse Events from Immune Checkpoint Inhibitors: Lessons Learned from Our Practice

Medicina, Journal Year: 2024, Volume and Issue: 60(3), P. 373 - 373

Published: Feb. 22, 2024

Background: New oncologic therapies, including immune checkpoint inhibitors (ICIs), have revolutionized the survival and prognosis of cancer patients. However, these therapies are often complicated by immune-related adverse effects (irAEs) that may impact quality life potentially limit their use. Among events psoriasis psoriatic arthritis develop de novo or flare under treatment with ICIs. Given exceptional status patients receiving ICIs, managing conditions without interfering effect prove very challenging. Aim: To review literature data on ICI-induced exacerbation development, to present our own experience, discuss pathogenic mechanisms underlying this association optimal therapeutic approach for Case Reports: We report three cases two required systemic treatment. Oral acitretin successfully controlled lesions in allowed continuation immunotherapy. Literature Review: performed a medical search across several databases (PubMed, Medline, Google Scholar) using terms “immune inhibitor-induced psoriasis/psoriasiform dermatitis/psoriasis arthritis”. identified revised 80 relevant publications reported 1102 and/or induced exacerbated assessed type cancer, agent involved, clinical form psoriasis, presence absence arthritis, personal family history age, gender, time until onset skin lesions, specific recommended, need ICI discontinuation, patient’s outcome. Conclusions: As ICIs represent fairly novel therapy, is only now unraveling. Psoriasis following initiation immunotherapy one such example, as more reports case series being published. Awareness relationship between prompt recognition, adequate skin-directed essential avoidance worsening, treatments interfere ICIs’ effects, discontinuation latter. In generally accepted guidelines, it advisable treat severe, widespread drugs do not impair thus alter prognosis.

Language: Английский

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GenotypingHLAalleles to predict the development of Severe cutaneous adverse drug reactions (SCARs): state-of-the-art

Expert Opinion on Drug Metabolism & Toxicology, Journal Year: 2021, Volume and Issue: 17(9), P. 1049 - 1064

Published: June 19, 2021

Introduction: Pharmacogenomics has great potential in reducing drug-induced severe cutaneous adverse drug reactions (SCARs). Pharmacogenomic studies have revealed an association between HLA genes and SCARs including acute generalized exanthematous pustulosis (AGEP), reaction with eosinophilia systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN).Areas covered: Pharmacogenomics-guided therapy could prevent hypersensitivity reactions. The US Food Drug Administration (FDA), Clinical Pharmacogenetics Implementation Consortium (CPIC), Dutch Working Group (DPWG) provided guidelines the translation of clinically relevant evidence-based pharmacogenomics research into clinical practice. In this review, we intended to summarize significant alleles associated induced by different drugs populations. We also genetic non-genetic factors cost-effectiveness screening tests.Expert opinion: effectiveness on a wider scale practice requires resources, state-of-the-art laboratory; multidisciplinary team approach health care provider education engagement; decision support alert system via electronic medical record (EMR); laboratory standards quality assurance; evidence cost-effectiveness; cost tests reimbursement.

Language: Английский

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Assessment of Cutaneous and Mucosal Direct Immunofluorescence Testing Practices in the US

JAMA Dermatology, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Direct immunofluorescence (DIF) testing has been an important ancillary tool for the diagnosis of various inflammatory mucocutaneous conditions more than 50 years. Current DIF test panels are based on historical clinical descriptions; few studies have rigorously addressed preanalytical, analytical, and/or postanalytical aspects, and even fewer replicated or validated. Recent unresolved key issues include whether should be triaged truncated indication histopathologic findings. To assess levels consensus regarding practical aspects among immunodermatology specialists in US. Using modified Delphi methods with a priori characterized criteria, survey containing 54 statements pertaining to was created distributed consensus. Statements not initially reaching were discussed 2 live virtual sessions, which supplemented by relevant literature review free-text comments. These then reassessed second survey. Immunodermatology US academic institution-based independent laboratories invited serving as laboratory medical directors, authoring pertinent literature, delivering talks at major conferences referral. The first conducted from January February 2024, March April 2024. primary measured outcome degree practice, including triage histopathology/dermatopathology findings panel tailored truncations indication. A total 23 respondents invitation had mean (SD) 18.5 (11.1) years median (range) 20.0 (1.5-46.0) practice. Consensus achieved 46 (85.2%) initial additional 4 (50 [92.6%]). Strong found against truncation round. general acceptability triaging specimens histopathology remained without after both surveys. Overall, participating agreed many testing, matters queried previously. also revealed areas continued controversy identified prioritized future study.

Language: Английский

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