PMID- 37270183
OWN - NLM
STAT- MEDLINE
DCOM- 20230605
LR  - 20230908
IS  - 2051-1426 (Electronic)
IS  - 2051-1426 (Linking)
VI  - 11
IP  - 6
DP  - 2023 Jun
TI  - Management of immune-related cutaneous adverse events with dupilumab.
LID - 10.1136/jitc-2023-007324 [doi]
LID - e007324
AB  - 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.
CI  - (c) 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.
FAU - Kuo, Alyce Mei-Shiuan
AU  - Kuo AM
AUID- ORCID: 0000-0002-6780-6506
AD  - Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer 
      Center, New York, New York, USA.
FAU - Gu, Stephanie
AU  - Gu S
AD  - Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer 
      Center, New York, New York, USA.
FAU - Stoll, Joseph
AU  - Stoll J
AD  - Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer 
      Center, New York, New York, USA.
AD  - Department of Dermatology, Weill Cornell Medical College, New York, New York, 
      USA.
FAU - Moy, Andrea P
AU  - Moy AP
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New 
      York, USA.
FAU - Dusza, Stephen W
AU  - Dusza SW
AD  - Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer 
      Center, New York, New York, USA.
FAU - Gordon, Allison
AU  - Gordon A
AD  - Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer 
      Center, New York, New York, USA.
AD  - Department of Dermatology, Weill Cornell Medical College, New York, New York, 
      USA.
FAU - Haliasos, Elena C
AU  - Haliasos EC
AD  - Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer 
      Center, New York, New York, USA.
FAU - Janjigian, Yelena
AU  - Janjigian Y
AD  - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New 
      York, USA.
FAU - Kraehenbuehl, Lukas
AU  - Kraehenbuehl L
AD  - Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer 
      Center, New York, New York, USA.
FAU - Quigley, Elizabeth A
AU  - Quigley EA
AD  - Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer 
      Center, New York, New York, USA.
FAU - Chapman, Paul
AU  - Chapman P
AUID- ORCID: 0000-0003-1618-0811
AD  - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New 
      York, USA.
FAU - Lacouture, Mario E
AU  - Lacouture ME
AD  - Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer 
      Center, New York, New York, USA.
AD  - Department of Dermatology, Weill Cornell Medical College, New York, New York, 
      USA.
FAU - Markova, Alina
AU  - Markova A
AD  - Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer 
      Center, New York, New York, USA markovaa@mskcc.org.
AD  - Department of Dermatology, Weill Cornell Medical College, New York, New York, 
      USA.
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - J Immunother Cancer
JT  - Journal for immunotherapy of cancer
JID - 101620585
RN  - 420K487FSG (dupilumab)
RN  - 0 (Antibodies, Monoclonal)
SB  - IM
MH  - Humans
MH  - *Antibodies, Monoclonal/therapeutic use
MH  - Retrospective Studies
MH  - Prospective Studies
MH  - *Dermatitis/drug therapy
PMC - PMC10255229
OTO - NOTNLM
OT  - Immune Checkpoint Inhibitors
OT  - Ipilimumab
OT  - Nivolumab
OT  - Th1-Th2 Balance
COIS- 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.
EDAT- 2023/06/04 01:08
MHDA- 2023/06/05 06:43
PMCR- 2023/06/02
CRDT- 2023/06/03 20:42
PHST- 2023/05/21 00:00 [accepted]
PHST- 2023/06/05 06:43 [medline]
PHST- 2023/06/04 01:08 [pubmed]
PHST- 2023/06/03 20:42 [entrez]
PHST- 2023/06/02 00:00 [pmc-release]
AID - jitc-2023-007324 [pii]
AID - 10.1136/jitc-2023-007324 [doi]
PST - ppublish
SO  - J Immunother Cancer. 2023 Jun;11(6):e007324. doi: 10.1136/jitc-2023-007324.