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. 2023 Jun;11(6):e007324.
doi: 10.1136/jitc-2023-007324.

Management of immune-related cutaneous adverse events with dupilumab

Alyce Mei-Shiuan Kuo  1 , Stephanie Gu  1 , Joseph Stoll  1   2 , Andrea P Moy  3 , Stephen W Dusza  1 , Allison Gordon  1   2 , Elena C Haliasos  1 , Yelena Janjigian  4 , Lukas Kraehenbuehl  1 , Elizabeth A Quigley  1 , Paul Chapman  4 , Mario E Lacouture  1   2 , Alina Markova  5   2
Affiliations

Management of immune-related cutaneous adverse events with dupilumab

Alyce Mei-Shiuan Kuo et al. J Immunother Cancer. 2023 Jun.

Abstract

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.

Keywords: Immune Checkpoint Inhibitors; Ipilimumab; Nivolumab; Th1-Th2 Balance.

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Conflict of interest statement

Competing interests: YJ receives research funding from Bayer, Bristol-Myers Squibb, Cycle for Survival, Department of Defense, Eli Lilly, Fred’s Team, Genentech/Roche, Merck, NCI, RGENIX, is on the advisory board or serves as a consultant for Amerisource Bergen, Arcus Biosciences, AstraZeneca, Basilea Pharmaceutica, Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Geneos Therapeutics, GlaxoSmithKline, Imedex, Imugene, Lynx Health, Merck, Merck Serono, Mersana Therapeutics, Michael J. Hennessy Associates, Paradigm Medical Communications, PeerView Institute, Pfizer, Research to Practice, RGENIX, Seagen, Silverback Therapeutics, Zymeworks Inc., and has stock options with RGENIX. EAQ receives royalties from UpToDate. PC is a consultant for Merck, Immunocore, AstraZeneca, and Pfizer and has equity interest in Rgenix. MEL has a consultant role with Johnson and Johnson, Novocure, QED, Bicara, Janssen, Novartis, F. Hoffmann-LaRoche AG, EMD Serono, AstraZeneca, Innovaderm, Deciphera, DFB, Azitra, Kintara, RBC/La Roche Posay, Trifecta, Varsona, Genentech, Loxo, Seattle Genetics, Lutris, On Quality, Azitra, Roche, Oncoderm, NCODA, and Apricity. MEL receives research funding from Lutris, Paxman, Novocure, J&J, US Biotest, OQL, Novartis, and AstraZeneca. AM receives research funding from Incyte Corporation and Amryt Pharma; consults for Blueprint Medicines, ADC Therapeutics, Alira Health, OnQuality, Protagonist Therapeutics, and Janssen; and receives royalties from up to date.

Figures

Figure 1
Figure 1
Treatments used to manage ircAEs before and after intervention with dupilumab. ircAE, immune-related cutaneous adverse event.
Figure 2
Figure 2
Pre to post dupilumab changes in blood eosinophils, total serum IgE, and IL-5 of patients with ircAEs. Solid lines represent the trajectories of the means from before to after treatment with dupilumab. IgE, immunoglobulin E; IL-5, interleukin 5; ircAEs, immune-related cutaneous adverse events.
See this image and copyright information in PMC

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