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

Journal of Clinical Oncology, Год журнала: 2021, Номер 39(36), С. 4073 - 4126

Опубликована: Ноя. 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.

Язык: Английский

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Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events

Journal for ImmunoTherapy of Cancer, Год журнала: 2021, Номер 9(6), С. e002435 - e002435

Опубликована: Июнь 1, 2021

Immune checkpoint inhibitors (ICIs) are the standard of care for treatment several cancers. While these immunotherapies have improved patient outcomes in many clinical settings, they bring accompanying risks toxicity, specifically immune-related adverse events (irAEs). There is a need clear, effective guidelines management irAEs during ICI treatment, motivating Society Immunotherapy Cancer (SITC) to convene an expert panel develop practice guideline. The discussed recognition and single combination ultimately developed evidence- consensus-based recommendations assist medical professionals decision-making improve patients.

Язык: Английский

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Immune checkpoint inhibitor–related dermatologic adverse events

Journal of the American Academy of Dermatology, Год журнала: 2020, Номер 83(5), С. 1255 - 1268

Опубликована: Май 23, 2020

Язык: Английский

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Tolerability of BRAF/MEK inhibitor combinations: adverse event evaluation and management

ESMO Open, Год журнала: 2019, Номер 4(3), С. e000491 - e000491

Опубликована: Янв. 1, 2019

The inhibition of the mitogen-activated protein kinases signalling pathway through combined use BRAF and MEK inhibitors (BRAFi+MEKi) represents an established therapeutic option in patients with BRAF-mutated, advanced melanoma. These efficient therapies are well tolerated mostly moderate reversible side effects a discontinuation rate due to adverse events 11.5%–15.7%. Median duration therapy ranges between 8.8 11.7 months. Based on data from confirmatory trials, safety profiles three BRAFi+MEKi combinations were reviewed, that is, dabrafenib plus trametinib, vemurafenib cobimetinib encorafenib binimetinib. Many class effects, such as cutaneous, gastrointestinal, ocular, cardiac musculoskeletal events; some substance associated. Fever (dabrafenib) photosensitivity (vemurafenib) most common clinically prominent examples. Other less frequent association one is strong anaemia, facial paresis (encorafenib), neutropenia (dabrafenib), skin rash, QTc prolongation increased liver function tests (vemurafenib). This narrative review provides recommendations for monitoring, event evaluation management focusing relevant regimens.

Язык: Английский

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Drug-Induced Hypersensitivity Syndrome (DIHS)/Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS): Clinical Features and Pathogenesis

The Journal of Allergy and Clinical Immunology In Practice, Год журнала: 2022, Номер 10(5), С. 1155 - 1167.e5

Опубликована: Фев. 15, 2022

Язык: Английский

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Management of Dermatologic Events Associated With the Nectin-4-directed Antibody-Drug Conjugate Enfortumab Vedotin

The Oncologist, Год журнала: 2022, Номер 27(3), С. e223 - e232

Опубликована: Янв. 24, 2022

Enfortumab vedotin is a first-in-class Nectin-4-directed antibody-drug conjugate approved by the US Food and Drug Administration for treatment of patients with locally advanced or metastatic urothelial cancer (la/mUC) previously treated platinum-based chemotherapy programmed death receptor-1/programmed death-ligand 1 (PD-1/L1) inhibitor, la/mUC who are ineligible cisplatin-based have received one more prior lines therapy. only drug to demonstrated survival benefit versus in randomized controlled trial PD-1/L1 inhibitor. The development dermatologic events following administration enfortumab anticipated given expression Nectin-4 epidermal keratinocytes skin appendages (eg, sweat glands hair follicles). There potential rare but severe possibly fatal cutaneous adverse reactions, including Stevens-Johnson syndrome toxic necrosis, as described boxed warning prescribing information vedotin. This manuscript describes presumed pathophysiology manifestations reactions related vedotin, presents recommendations prevention treatment, provide oncologists other healthcare providers an awareness these best anticipate manage them.

Язык: Английский

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Immune-related adverse events in various organs caused by immune checkpoint inhibitors

Allergology International, Год журнала: 2022, Номер 71(2), С. 169 - 178

Опубликована: Янв. 29, 2022

Current cancer immunotherapies target immune checkpoint molecules such as the inhibitory receptor programmed cell death-1 (PD-1), one of its ligands, death ligand-1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), a competitive ligand for CD28 binding to stimulatory receptors CD80 CD86. Multiple biological drugs use monoclonal antibodies targeting PD-1, PD-L1 CTLA-4 immunotherapies. These are termed inhibitors (ICIs). However, activation system by ICIs can induce development immune-related adverse events (irAEs), which affect multiple organ systems. The most frequent irAEs cutaneous mimic various types spontaneous skin disorders. Most classified autoimmune conditions mediated ICI-activated CD8+ T cells, some also related activated B cells production pathogenic antibodies. Interestingly, blockade mainly induces inhibition Treg cells. On other hand, mechanisms underlying anti-PD-1/PD-L1 ICI-induced more complicated. PD-1 is expressed on binds not only PD-L1, but PD-L2. role dominant in Th1 Th17 immunity, while PD-L2 works Th2 immunity. Better understanding will allow better management improve outcomes quality life patients.

Язык: Английский

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Cutaneous manifestations associated with immune checkpoint inhibitors

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Фев. 20, 2023

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block key mediators of tumor-mediated immune evasion. The frequency its use has increased rapidly and extended to numerous cancers. ICIs target molecules, such as programmed cell death protein 1 (PD-1), PD ligand (PD-L1), T activation, including cytotoxic T-lymphocyte-associated protein-4 (CTLA-4). However, ICI-driven alterations in the system can induce various immune-related adverse events (irAEs) affect multiple organs. Among these, cutaneous irAEs most common often first develop. Skin manifestations characterized by a wide range phenotypes, maculopapular rash, psoriasiform eruption, lichen planus-like pruritus, vitiligo-like depigmentation, bullous diseases, alopecia, Stevens-Johnson syndrome/toxic epidermal necrolysis. In terms pathogenesis, mechanism remains unclear. Still, several hypotheses have been proposed, activation cells against antigens normal tissues tumor cells, release proinflammatory cytokines associated with effects specific tissues/organs, association human leukocyte antigen variants organ-specific irAEs, acceleration concurrent medication-induced drug eruptions. Based on recent literature, this review provides an overview each ICI-induced skin manifestation epidemiology focuses mechanisms underlying irAEs.

Язык: Английский

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Cutaneous Immune-Related Adverse Events (irAEs) to Immune Checkpoint Inhibitors: A Dermatology Perspective on Management

Journal of Cutaneous Medicine and Surgery, Год журнала: 2020, Номер 25(1), С. 59 - 76

Опубликована: Авг. 3, 2020

Immune checkpoint inhibitors have proven to be efficacious for a broad spectrum of solid organ malignancies. These monoclonal antibodies lead cytotoxic T-cell activation and subsequent elimination cancer cells. However, they can also immune intolerance immune-related adverse event (irAEs) that are new specific these therapies. Cutaneous irAEs the most common, arising in up 34% patients on PD-1 43% 45% CTLA-4 inhibitors. The common skin manifestations include maculopapular eruption, pruritus, vitiligo-like lesions. A grading system has been proposed, which guides management cutaneous based percent body surface area (BSA) involved. may prompt clinicians reduce drug doses, add systemic steroids regiment, and/or discontinue lifesaving immunotherapy. Thus, goal is early identification concurrent minimize treatment interruptions. We emphasize here severity reaction should not graded BSA involvement alone, but rather nature primary pathology. For instance, eruptions rarely affect <30% often managed conservatively with skin-directed therapies, while Stevens-Johnson syndrome (SJS) affecting even 5% aggressively immunotherapy discontinued at once. There limited literature available studies present anecdotal evidence. review strategies provide recommendations psoriatic, immunobullous, maculopapular, lichenoid, acantholytic eruptions, vitiligo, alopecias, vasculitides, SJS/toxic epidermal necrolysis, other related toxicities.

Язык: Английский

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Toxic Epidermal Necrolysis and Steven–Johnson Syndrome: A Comprehensive Review

Advances in Wound Care, Год журнала: 2019, Номер 9(7), С. 426 - 439

Опубликована: Дек. 18, 2019

Significance: Toxic epidermal necrolysis (TEN) and Steven-Johnson syndrome (SJS) are potentially fatal acute mucocutaneous vesiculobullous disorders. Evidence to date suggests that outcomes for patients with both TEN SJS largely dependent on stopping the causative agent, followed by supportive care appropriate wound management in a specialized burns unit. These life-threatening conditions characterized widespread full-thickness cutaneous mucosal necrosis. This article outlines approach holistic of such patients, unit, highlighting various practical aspects prevent complications as infection, adhesions, ocular scaring. Recent Advances: There is improved understanding pain morbidity regard type frequency dressing changes. More modern dressings, nanocrystalline, currently favored they may be kept situ longer periods. The most recent evidence systemic agents, corticosteroids cyclosporine, novel treatments, also discussed. Critical Issues: Following cessation culprit trigger, unit important step. It now understood multidisciplinary team essential these patients. admission dermatology, ear, nose, throat surgery, ophthalmology, urology, colorectal gynecology should all consulted disease sequelae. Future Directions: Looking forward, research aimed at achieving prospective data efficacy immunomodulating agents types. Tertiary centers units develop policies ensure relevant teams promptly avoid complications.

Язык: Английский

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