Immune checkpoint inhibitors in patients with pre-existing psoriasis: safety and efficacy

Halle, Briana R.; Warner, Allison Betof; Zaman, Farzana; Haydon, Andrew; Bhave, Prachi; Dewan, Anna K.; Ye, Fei; Irlmeier, Rebecca; Mehta, Paras; Kurtansky, Nicholas; Lacouture, Mario E.; Hassel, Jessica C.; Choi, Jacob; Sosman, Jeffrey A.; Chandra, Sunandana; Otto, Tim; Sullivan, Ryan J.; Mooradian, Meghan J.; Chen, Steven T; Dimitriou, Florentia; Long, Georgina V.; Carlino, Matteo S.; Menzies, Alexander M.; Johnson, Douglas B.; Rotemberg, Veronica

doi:10.1136/jitc-2021-003066

Cited by 40 publications

(44 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Patients with pre-existing autoimmune disorders are largely excluded from clinical trials, and their long-term outcomes are not well described. Data from a number of studies suggest that these patients have similar or slightly higher rates of classic irAEs, and similar antitumour responses compared with those of individuals without autoimmune disease, although these patients also have high incidences of autoimmune flares (20–25%) 142 – 145 . In our anecdotal experience, any autoimmune disease flares will usually improve following treatment discontinuation, although the long-term outcomes in these patients need to be studied in more detail.…”

Section: Chronic Iraesmentioning

confidence: 99%

Immune-checkpoint inhibitors: long-term implications of toxicity

et al. 2022

View full text Add to dashboard Cite

The development of immune-checkpoint inhibitors (ICIs) has heralded a new era in cancer treatment, enabling the possibility of long-term survival in patients with metastatic disease, and providing new therapeutic indications in earlier-stage settings. As such, characterizing the long-term implications of receiving ICIs has grown in importance. An abundance of evidence exists describing the acute clinical toxicities of these agents, although chronic effects have not been as well catalogued. Nonetheless, emerging evidence indicates that persistent toxicities might be more common than initially suggested. While generally low-grade, these chronic sequelae can affect the endocrine, rheumatological, pulmonary, neurological and other organ systems. Fatal toxicities also comprise a diverse set of clinical manifestations and can occur in 0.4–1.2% of patients. This risk is a particularly relevant consideration in light of the possibility of long-term survival. Finally, the effects of immune-checkpoint blockade on a diverse range of immune processes, including atherosclerosis, heart failure, neuroinflammation, obesity and hypertension, have not been characterized but remain an important area of research with potential relevance to cancer survivors. In this Review, we describe the current evidence for chronic immune toxicities and the long-term implications of these effects for patients receiving ICIs.

show abstract

Section: Chronic Iraesmentioning

confidence: 99%

Immune-checkpoint inhibitors: long-term implications of toxicity

et al. 2022

View full text Add to dashboard Cite

show abstract

“…High grade psoriasiform DAEs to anti-CTLA-4 and anti-PD-1/PD-L1 blockade have been widely reported in the literature ( 53 – 56 ). In FAERS, 152 cases of psoriasiform DAEs have been recorded in association with pembrolizumab, 40 with ipilimumab, 243 with nivolumab, 57 with atezolizumab, 5 with avelumab, 24 with durvalumab, and 4 with cemiplimab.…”

Section: High Grade Psoriasiform Dermatologic Adverse Eventsmentioning

confidence: 99%

“…Seven patients experienced grade 3–4 psoriasiform DAEs and 16 (21%) required systemic therapy. Of the 15 patients with pre-existing psoriatic arthritis prior to ICB, 6 experienced arthritis flares ( 56 ). Notably, progression-free survival was significantly longer in patients who experienced a psoriasis flare compared to those who did not (39 vs. 8.7 months, p = 0.049) ( 56 ).…”

Section: High Grade Psoriasiform Dermatologic Adverse Eventsmentioning

confidence: 99%

“…Of the 15 patients with pre-existing psoriatic arthritis prior to ICB, 6 experienced arthritis flares ( 56 ). Notably, progression-free survival was significantly longer in patients who experienced a psoriasis flare compared to those who did not (39 vs. 8.7 months, p = 0.049) ( 56 ). When biopsied, psoriasiform DAEs show parakeratosis, diminished granular layers, and acanthosis, with varying concomitant spongiosis ( 14 ).…”

Section: High Grade Psoriasiform Dermatologic Adverse Eventsmentioning

confidence: 99%

See 1 more Smart Citation

High Grade Dermatologic Adverse Events Associated With Immune Checkpoint Blockade for Cancer

Kuo

Markova

2022

Front. Med.

View full text Add to dashboard Cite

Immune checkpoint blockade (ICB) improves survival in many types of cancers including melanoma, non-small cell lung, renal cell, breast, and cervical cancers. However, many of these therapies are also associated with high grade dermatologic adverse events (DAEs), including Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), SJS/TEN-like reactions, high grade maculopapular and psoriasiform rashes, autoimmune bullous eruptions, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), which may limit their tolerability and use. It is important to properly identify and treat DAEs to ICB because these DAEs may be associated with positive anti-tumor response and patients may have limited options for alternative anti-cancer therapeutics. In this review, we describe high grade DAEs to increasingly used ICB agents, which target CTLA-4 and PD-1 or its ligand, PD-L1 and enable the immune system to target cancer cells. We further differentiate life-threatening adverse reactions from mimickers and report cases of serious DAEs which have been recorded in association with ICB through the FDA Adverse Events Reporting System (FAERS), which is an archive of adverse events associated with various drugs and therapeutic biologic products reported voluntarily by consumers and healthcare professionals as well as mandatorily by manufacturers. Lastly, we summarize management recommendations for these adverse events and discuss knowledge and evidence gaps in this area.

show abstract

“…Ein Absetzen der ICI-Therapie war in 7 % erforderlich. Die Dauer bis zur Tumorprogression war bei Patienten mit Zunahme der Psoriasisaktivität fast 5-fach länger [25]. In einer anderen Serie wurde eine Aktivitätszunahme vorbestehender Autoimmunerkrankungen in 28 % sowie das Auftreten zusätzlicher Autoimmunerkrankungen in 21 % beobachtet.…”

Section: Klassenspezifische Nebenwirkungen Von Checkpoint-inhibitoren...unclassified

Uveitisinduktion durch immunonkologische Therapien, speziell Checkpoint-Inhibitoren

Garweg

2022

Klin Monbl Augenheilkd

View full text Add to dashboard Cite

Zusammenfassung Hintergrund Immun-Checkpoint- und BRAF-/MEK-Inhibitoren (ICI) haben eine zentrale Stellung in der Krebstherapie eingenommen, da sie eine erhebliche Lebensverlängerung bei einer guten Verträglichkeit und Lebensqualität bewirken. Sie sind jedoch mit stoffklassenspezifischen, nicht toxischen immunologischen Nebenwirkungen, darunter auch Entstehung einer Uveitis, behaftet. In dieser Übersicht soll der aktuelle Kenntnisstand zu Wirkprinzip und systemischen und okulären Nebenwirkungen der ICI dargestellt werden. Methoden Dieser Übersicht liegt eine Literatursuche in PubMed, der Datenbank des National Institute of Health der USA (https://www.ncbi.nlm.nih.gov/pubmed) mit den Stichworten „uveitis“ AND „drug-induced“ AND/OR „immune checkpoint inhibitor“ zugrunde. Alle relevant erscheinenden Publikationen der letzten 5 Jahre wurden zusammen mit den darin zitierten Querverweisen ausgewertet. Ergebnisse Ein klassenspezifisches Phänomen der sonst gut verträglichen ICI ist ihre Fähigkeit, eine systemische und okuläre Autoimmunität auszulösen. Diese unterscheidet sich von toxischen Nebenwirkungen durch ihre Dosisunabhängigkeit. Okuläre Nebenwirkungen treten bei 3% der Patienten auf, wobei ein Melanom als Grunderkrankung und eine Therapie mit Pembrolizumab das Risiko um ein Mehrfaches erhöhen. Eine frühe Diagnose und systemische Steroidtherapie dieser potenziell lebensbedrohlichen Nebenwirkung erlauben in > 90% die Erhaltung der Sehfunktion und Lebensqualität, ohne die ICI-Therapie abzusetzen. Schlussfolgerung Das therapeutische Ansprechen von Malignomen auf ICI bezüglich des Überlebens und der Verträglichkeit, insbesondere bei Melanomen, lässt eine zunehmende Anwendung von ICI auch in Therapiekombinationen und damit eine Zunahme der immunologischen Komplikationen im klinischen Alltag erwarten. In Anbetracht einer Mortalität von unbehandelt bis zu 3% infolge immunvermittelter Nebenwirkungen an multiplen Organen ist eine rasche interdisziplinäre Abklärung und rechtzeitige aggressive Behandlung zwingend, führt aber meist auch zu erfreulichen funktionellen Ergebnissen.

show abstract

Immune checkpoint inhibitors in patients with pre-existing psoriasis: safety and efficacy

Cited by 40 publications

References 38 publications

Immune-checkpoint inhibitors: long-term implications of toxicity

Immune-checkpoint inhibitors: long-term implications of toxicity

High Grade Dermatologic Adverse Events Associated With Immune Checkpoint Blockade for Cancer

Uveitisinduktion durch immunonkologische Therapien, speziell Checkpoint-Inhibitoren

Contact Info

Product

Resources

About