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Management of immune-related cutaneous adverse events with dupilumab

Immune checkpoint inhibitors (ICI) target the PD-1/PD-L1 and CTLA-4 pathways and allows the immune system to deliver antitumor effects. However, it is also associated with well-documented immune-related cutaneous adverse events (ircAEs), affecting up to 70–90% of patients on ICI. In this study, we d...

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Autores principales: Kuo, Alyce Mei-Shiuan, Gu, Stephanie, Stoll, Joseph, Moy, Andrea P, Dusza, Stephen W, Gordon, Allison, Haliasos, Elena C, Janjigian, Yelena, Kraehenbuehl, Lukas, Quigley, Elizabeth A, Chapman, Paul, Lacouture, Mario E, Markova, Alina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10255229/
https://www.ncbi.nlm.nih.gov/pubmed/37270183
http://dx.doi.org/10.1136/jitc-2023-007324
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author Kuo, Alyce Mei-Shiuan
Gu, Stephanie
Stoll, Joseph
Moy, Andrea P
Dusza, Stephen W
Gordon, Allison
Haliasos, Elena C
Janjigian, Yelena
Kraehenbuehl, Lukas
Quigley, Elizabeth A
Chapman, Paul
Lacouture, Mario E
Markova, Alina
author_facet Kuo, Alyce Mei-Shiuan
Gu, Stephanie
Stoll, Joseph
Moy, Andrea P
Dusza, Stephen W
Gordon, Allison
Haliasos, Elena C
Janjigian, Yelena
Kraehenbuehl, Lukas
Quigley, Elizabeth A
Chapman, Paul
Lacouture, Mario E
Markova, Alina
author_sort Kuo, Alyce Mei-Shiuan
collection PubMed
description Immune checkpoint inhibitors (ICI) target the PD-1/PD-L1 and CTLA-4 pathways and allows the immune system to deliver antitumor effects. However, it is also associated with well-documented immune-related cutaneous adverse events (ircAEs), affecting up to 70–90% of patients on ICI. In this study, we describe the characteristics of and patient outcomes with ICI-associated steroid-refractory or steroid-dependent ircAEs treated with dupilumab. Patients with ircAEs treated with dupilumab between March 28, 2017, and October 1, 2021, at Memorial Sloan Kettering Cancer Center were included in this retrospective study, which assessed the rate of clinical response of the ircAE to dupilumab and any associated adverse events (AEs). Laboratory values were compared before and after dupilumab. All available biopsies of the ircAEs were reviewed by a dermatopathologist. Thirty-four of 39 patients (87%, 95% CI: 73% to 96%) responded to dupilumab. Among these 34 responders, 15 (44.1%) were complete responders with total ircAE resolution and 19 (55.9%) were partial responders with significant clinical improvement or reduction in severity. Only 1 patient (2.6%) discontinued therapy due to AEs, specifically, injection site reaction. Average eosinophil counts decreased by 0.2 K/mcL (p=0.0086). Relative eosinophils decreased by a mean of 2.6% (p=0.0152). Total serum immunoglobulin E levels decreased by an average of 372.1 kU/L (p=0.0728). The most common primary inflammatory patterns identified on histopathological examination were spongiotic dermatitis (n=13, 33.3%) and interface dermatitis (n=5, 12.8%). Dupilumab is a promising option for steroid-refractory or steroid-dependent immune-related cutaneous adverse events, particularly those that are eczematous, maculopapular, or pruritic. Among this cohort, dupilumab was well-tolerated with a high overall response rate. Nonetheless, prospective, randomized, controlled trials are warranted to confirm these observations and confirm its long-term safety.
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spelling pubmed-102552292023-06-10 Management of immune-related cutaneous adverse events with dupilumab Kuo, Alyce Mei-Shiuan Gu, Stephanie Stoll, Joseph Moy, Andrea P Dusza, Stephen W Gordon, Allison Haliasos, Elena C Janjigian, Yelena Kraehenbuehl, Lukas Quigley, Elizabeth A Chapman, Paul Lacouture, Mario E Markova, Alina J Immunother Cancer Clinical/Translational Cancer Immunotherapy Immune checkpoint inhibitors (ICI) target the PD-1/PD-L1 and CTLA-4 pathways and allows the immune system to deliver antitumor effects. However, it is also associated with well-documented immune-related cutaneous adverse events (ircAEs), affecting up to 70–90% of patients on ICI. In this study, we describe the characteristics of and patient outcomes with ICI-associated steroid-refractory or steroid-dependent ircAEs treated with dupilumab. Patients with ircAEs treated with dupilumab between March 28, 2017, and October 1, 2021, at Memorial Sloan Kettering Cancer Center were included in this retrospective study, which assessed the rate of clinical response of the ircAE to dupilumab and any associated adverse events (AEs). Laboratory values were compared before and after dupilumab. All available biopsies of the ircAEs were reviewed by a dermatopathologist. Thirty-four of 39 patients (87%, 95% CI: 73% to 96%) responded to dupilumab. Among these 34 responders, 15 (44.1%) were complete responders with total ircAE resolution and 19 (55.9%) were partial responders with significant clinical improvement or reduction in severity. Only 1 patient (2.6%) discontinued therapy due to AEs, specifically, injection site reaction. Average eosinophil counts decreased by 0.2 K/mcL (p=0.0086). Relative eosinophils decreased by a mean of 2.6% (p=0.0152). Total serum immunoglobulin E levels decreased by an average of 372.1 kU/L (p=0.0728). The most common primary inflammatory patterns identified on histopathological examination were spongiotic dermatitis (n=13, 33.3%) and interface dermatitis (n=5, 12.8%). Dupilumab is a promising option for steroid-refractory or steroid-dependent immune-related cutaneous adverse events, particularly those that are eczematous, maculopapular, or pruritic. Among this cohort, dupilumab was well-tolerated with a high overall response rate. Nonetheless, prospective, randomized, controlled trials are warranted to confirm these observations and confirm its long-term safety. BMJ Publishing Group 2023-06-02 /pmc/articles/PMC10255229/ /pubmed/37270183 http://dx.doi.org/10.1136/jitc-2023-007324 Text en © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Clinical/Translational Cancer Immunotherapy
Kuo, Alyce Mei-Shiuan
Gu, Stephanie
Stoll, Joseph
Moy, Andrea P
Dusza, Stephen W
Gordon, Allison
Haliasos, Elena C
Janjigian, Yelena
Kraehenbuehl, Lukas
Quigley, Elizabeth A
Chapman, Paul
Lacouture, Mario E
Markova, Alina
Management of immune-related cutaneous adverse events with dupilumab
title Management of immune-related cutaneous adverse events with dupilumab
title_full Management of immune-related cutaneous adverse events with dupilumab
title_fullStr Management of immune-related cutaneous adverse events with dupilumab
title_full_unstemmed Management of immune-related cutaneous adverse events with dupilumab
title_short Management of immune-related cutaneous adverse events with dupilumab
title_sort management of immune-related cutaneous adverse events with dupilumab
topic Clinical/Translational Cancer Immunotherapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10255229/
https://www.ncbi.nlm.nih.gov/pubmed/37270183
http://dx.doi.org/10.1136/jitc-2023-007324
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