Principles of prophylactic and therapeutic management of skin toxicity during treatment with checkpoint inhibitors

Kamińska‐Winciorek, Grażyna; Cybulska-Stopa, Bożena; Ługowska, Iwona; Ziobro, Marek; Rutkowski, Piotr

doi:10.5114/ada.2018.80272

Cited by 26 publications

(25 citation statements)

References 38 publications

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“…Thereby, it is essential to properly educate patients and healthcare providers (physicians and nurses) and implement the management algorithms, not only based on use of steroids. The resolution of treatmentrelated adverse events of immunotherapy occur generally in less than 12 weeks with the exception of skin-related adverse events on nivolumab therapy, which resolve at significantly longer timelines [11,94]. Some events never resolveprimarily endocrine events, for which long-term hormonal therapy may be warrantedand some may have delayed onset even after withdrawal administration of immune checkpoint inhibitors.…”

Section: Discussionmentioning

confidence: 99%

“…Specific guidelines for treatment of these common toxicities are currently readily available [25][26][27][28]. Nevertheless clinicians should be aware that although the most common dermatologic toxicities of nivolumab are pruritis and rash, also bullous pemphigoid, Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) have been reported and these are potentially life-threatening conditions [11,26,29]. At the same time pneumonitis induced by nivolumab often is challenging in terms of differential diagnosis and imaging interpretation.…”

Section: Rare Iraes Of Nivolumab Treatment In Melanoma Patientsmentioning

confidence: 99%

“…In clinical practice irAEs are reported if any other etiology of adverse event is unknown, therefore etiology is expected to result from immune phenomena and to be inflammatory in nature [8]. Most irAEs of nivolumab are low grade and managed successfully with supportive care or symptomatic treatment using appropriate guidelines [9][10][11][12]. Most of these irAE up-to grade 4 are reversible after treatment interruption and/ or corticosteroid therapy in relevant doses (usually (methyl) prednisolone 1-2 mg/kg) [9,10].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

An update on the safety of nivolumab for the treatment of advanced melanoma

Czarnecka

Rutkowski

2020

Expert Opinion on Drug Safety

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Introduction: Due to its unique mechanism of action as an immune checkpoint inhibitor, nivolumab has high antitumor activity, but at the same time this mechanism is responsible for immune-related adverse events that may limit patients' safety and therapy continuation. Areas covered: Long-term safety of nivolumab including 5-year follow-up, safety of nivolumab treatment after ipilimumab therapy, safety of nivolumab in challenging subgroups (elderly, patients with brain metastases, patients with autoimmune disorders), safety of nivolumab in with rare melanoma subtypes (including mucosal melanoma), as well as specificity of AEs reported for nivolumab treatment in melanoma patients in comparison to other cancer types and other immunotherapy molecules, and impact of AEs on response rates and PFS on nivolumab treatment are discussed. Expert opinion: Search for biomarkers that would help us to identify patient populations that may suffer from severe nivolumab toxicity could help in selecting patients that should not be treated with this type of therapy. Novel combinations and immunotherapy drugs including use of NKTR-214 (IL-2 pathway), lymphocyte-activation gene 3 (LAG-3), local injections of talimogene laherparepvec (T-VEC), or systemic use of T-cell receptors agonists such as OX40, CD137, ICOS-1, could provide regimens with limited toxicity and higher activity.

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Section: Discussionmentioning

confidence: 99%

Section: Rare Iraes Of Nivolumab Treatment In Melanoma Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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An update on the safety of nivolumab for the treatment of advanced melanoma

Czarnecka

Rutkowski

2020

Expert Opinion on Drug Safety

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“…A pruritic maculopapular rash is the most common irAEs ( Fig [49]. Changes may also appear many months after the introduce of treatment [53]. In assessing the severity of lesions (CTCAE), the extent of the lesions and the negative impact on health-related quality of life is taking into account.…”

Section: Skin Toxicitymentioning

confidence: 99%

Immunotherapy of solid tumors: how safely treat the patients

Domagała‐Kulawik

Leszek

Owczarek

et al. 2020

Polish Archives of Internal Medicine

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Immunotherapy with immune checkpoint inhibitors (ICIs) was shown to improve survival of patients with solid tumors like: melanoma, renal carcinoma, non-small cell lung cancer, cutaneous carcinomas or head and neck carcinoma. However, a special type of ICIs toxicity is observed, namely non-infectious inflammation of different organs connected with autoimmunity known as immune related adverse events (irAEs). This non-infectious inflammation may affect different organs and systems as endocrine organs, the gastrointestinal tract, heart, skin and the nervous system. The lungs are also often involved and this condition is referred to as checkpoint inhibitor pneumonitis (CIP). ICIs toxicity is graded from 1 to 5 depending on the clinical course, the 5 grade being a fatal complication. Corticosteroids are the treatment of choice, generally with good efficacy. In some difficult cases, escalation of immunosuppression is required. The knowledge on irAEs should be promoted among clinicians of all specialties, nurses, patients and their families. The aim of this review is to present the wide spectrum of irAEs: clinical signs and symptoms, differential diagnosis, diagnostic procedures and treatment. The data are supported by our own clinical observations.

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“…Die genannten dermatologischen Nebenwirkungen sind in aller Regel einer Therapie gut zugänglich und erfordern üblicherweise keine Dosisreduktion oder gar einen Therapieabbruch [2,21]. Empfehlenswert ist die Verwendung topischer Glukokortikosteroide wie Mometasonfuroat-Creme oder im späteren Verlauf harnstoffhaltige und/oder rückfettende Externa.…”

Section: Allgemeines Nebenwirkungsprofilunclassified

Nebenwirkungsmanagement bei Immun‐Checkpoint‐Blockade durch CTLA‐4‐ und PD‐1‐Antikörper beim metastasierten Melanom – ein Update

Kähler

Hassel

Heinzerling

et al. 2020

J Deutsche Derma Gesell

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EinleitungDie Immun-Checkpoint-Inhibition (ICI) hat die medikamentöse Tumortherapie in den letzten zehn Jahren revolutioniert, wobei das metastasierte Melanom bei der Entwicklung dieser Therapie die führende Indikation war [1]. Eine Vielzahl von Immun-Checkpoints sind bekannt. Zur Tumortherapie zugelassene Antikörper sind momentan verfügbar zur Blockade der Checkpoints CTLA-4 (cytotoxic T-lymphocyte antigen 4, Ipilimumab) und PD-1 (programmed cell death protein 1, Nivolumab, Pembrolizumab, Cemiplimab) beziehungsweise dessen Liganden PD-L1 (Avelumab, Atezolizumab, Durvalumab). Diese Antikörper werden bei zahlreichen Tumorentitäten eingesetzt, neben den Hauttumoren (Melanom, kutanes Plattenepithelkarzinom und Merkelzellkarzinom) gehören dazu Bronchial-, Mamma-, Nieren-, Leber-, Harnblasen-und Kopf-Hals-Tumoren. Der therapeutische Eingriff in die Regulation des Immunsystems hat aber auch Nebenwirkungen, die auf dem Wirkmechanismus beruhen. So kann es zu Entzündungen in unterschiedlichen Organen kommen, die teilweise lebensbedrohlich sein können und ein schnelles Handeln erfordern. Dieser Artikel bietet ein Update zu unserer Übersicht von 2016 [2] und soll den aktuellen Kenntnisstand zu den Nebenwirkungen und dem Management von Immun-Checkpoint-Inhibitoren zusammenfassen. Eine so intensivierte Immunantwort bringt unvermeidlich auch Nebenwirkungen mit sich. Das Wissen um dieses Nebenwirkungsspektrum ist für die Prophylaxe und das Management notwendig. Es kommt zu Nebenwirkungen wie Colitis, Dermatitis, Hypophysitis, Thyreoiditis, Hepatitis und weiteren, selteneren Autoimmunphänomenen. Die Erkennung und Therapie der genannten Autoimmunnebenwirkungen sind inzwischen gut bekannt. Insbesondere die frühe Diagnose seltener, aber mit einer höheren Letalität verbundenen neurologischen oder kardiologischen Nebenwirkungen ist häufig schwierig. Dieses Update beschreibt das aktuelle Nebenwirkungsspektrum und -Management unter Immun-Checkpoint-Inhibition sowie neue Erkenntnisse zu diesem Themenfeld. SummaryCTLA-4 and PD-1 play a key role in tumor-induced downregulation of lymphocytic immune responses. Immune checkpoint inhibitors have been shown to alter the immune response to various cancer types. Anti-CTLA-4 and anti-PD-1 antibodies affect the interaction between tumor, antigen-presenting cells and T lymphocytes. Clinical studies of the anti-CTLA-4 antibody ipilimumab and the anti-PD-1 antibodies nivolumab and pembrolizumab have provided evidence of their positive effects on overall survival in melanoma patients. Combined treatment using ipilimumab and nivolumab has been shown to achieve five-year survival rates of 52 %. Such enhancement of the immune response is inevitably associated with adverse events. Knowledge of the spectrum of side effects is essential, both in terms of prevention and management. Adverse events include colitis, dermatitis, hypophysitis, thyroiditis, hepatitis and other, less common autoimmune phenomena. In recent years, considerable progress has been made in the detection and treatment of the aforemention...

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Principles of prophylactic and therapeutic management of skin toxicity during treatment with checkpoint inhibitors

Cited by 26 publications

References 38 publications

An update on the safety of nivolumab for the treatment of advanced melanoma

An update on the safety of nivolumab for the treatment of advanced melanoma

Immunotherapy of solid tumors: how safely treat the patients

Nebenwirkungsmanagement bei Immun‐Checkpoint‐Blockade durch CTLA‐4‐ und PD‐1‐Antikörper beim metastasierten Melanom – ein Update

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