10.5826/dpc.1303a143
text/xml
2160-9381
2910
en
Alessandra  Narcisi
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
Real-Life Safety and Effectiveness of Dupilumab in Patients With Concomitant Malignancies: A Case Series
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Research Letter
2023-07-31
2022-10-14
2023-07-31
2023-08-24
e2023143
Dermatol Pract Concept
Alessandra  Narcisi
2023/07/31
10.5826/dpc.1303a143
e2023143
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele; Dermatology Unit, IRCCS Humanitas Research Hospital, Rozzano, Italy
2160-9381
en
e2023143
Fowler E, Rosen J, Lev-Tov H, Yosipovitch G. Two Cancer Patients Receiving Dupilumab for Treatment of Atopic Dermatitis. Acta Derm Venereol. 2019;99(10):899-900. doi:10.2340/00015555-3201
Real-Life Safety and Effectiveness of Dupilumab in Patients With Concomitant Malignancies: A Case Series
https://dpcj.org/index.php/dpc/article/download/2910/2216
  Real-Life Safety and Effectiveness of Dupilumab
 in Patients with Concomitant Malignancies: a Case
                       Series
           Luigi Gargiulo1,2, Carlo Alberto Vignoli1,2, Andrea Cortese1,2, Luciano Ibba1,2,
                             Antonio Costanzo1,2, Alessandra Narcisi1,2


1 Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
2 Dermatology Unit, IRCCS Humanitas Research Hospital, Rozzano, Italy



Citation: Gargiulo L, Vignoli CA, Cortese A, Ibba L, Costanzo A Narcisi A. Real-Life Safety and Effectiveness of Dupilumab in Patients
With Concomitant Malignancies: A Case Series. Dermatol Pract Concept. 2023;13(3):e2023143. DOI: https://doi.org/10.5826/
dpc.1303a143
Accepted: December 12, 2022; Published: July 2023
Copyright: ©2023 Gargiulo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-
NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use,
distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing Interests: Antonio Costanzo has been a consultant and/or speaker for Abb-Vie, Almirall, Amgen, Janssen, Leo Pharma, Eli Lilly,
Galderma, Boehringer, Novartis, Pfizer, Sandoz, and UCB. Alessandra Narcisi has been a consultant and/or speaker for Abb-Vie, Almirall,
Amgen, Janssen, Leo Pharma, Eli Lilly, Boehringer, Novartis, Pfizer and UCB. Luigi Gargiulo, Carlo Alberto Vignoli, Andrea Cortese and
Luciano Ibba have nothing to disclose.
Authorship: All authors have contributed significantly to this publication.
Corresponding Author: Carlo Alberto Vignoli, Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4,
Pieve Emanuele (MI), 20090, Italy. E-mail: c.alberto.vignoli@gmail.com
Ethics / Patient Consent Statement: All included patients had provided written consent for retrospective study of data collected during
routine clinical practice.




Introduction                                                             Case Presentation
Dupilumab is a human monoclonal antibody which targets                   Ten patients started dupilumab after receiving a diagnosis of
the alpha subunit of the interleukin (IL)-4-Receptor, blocking           cancer (Table 1):
the signaling of both IL-13 and IL-4 and it is the first biologic
drug approved for moderate-to-severe atopic dermatitis [1].              • Three patients had previously undergone partial thyroid-
According to a systematic review from Braddock et al [2],                     ectomy for papillary thyroid carcinoma (4, 6 and 29 years
data on the role of IL-13 and IL-4 in carcinogenesis are con-                 before receiving dupilumab, respectively).
flicting and there is paucity of evidences regarding the use             • Two women had a history of ductal breast cancer: one
of dupilumab in patients with concomitant malignancies [3].                   received chemotherapy 12 years before the start of dup-
    We report our experience with 10 patients with previ-                     ilumab, while the second patient underwent surgery
ous history of cancer and 4 patients who developed a malig-                   6 years before.
nancy during treatment with dupilumab, from January 2019                 • Two patients had a diagnosis of prostatic cancer: one
to June 2022.                                                                 started dupilumab 4.5 years after the prostatectomy, while




Research Letter | Dermatol Pract Concept. 2023;13(3):e2023143                                                                             1
2
                                                                                             Table 1. Demographic data and characteristics of the malignancies of patients with history of cancer before
                                                                                                       the start of dupilumab and patients who developed cancer after the start of dupilumab
                                                                                                                                                                       Time
                                                                                                                                                                     Between
                                                                                                                                                                      Cancer
                                                                                                                                                         Date of    Diagnosis
                                                                                                                                             Date of    Dupilumab      and                                                  P-NRS
                                                                                                                                             Cancer     Treatment   Dupilumab   EASI at P-NRS at Date of Last EASI at Last  at Last
                                                                 N°   Sex Age            Type of Cancer            Cancer Treatment         Diagnosis      Start     (Months)   Baseline Baseline Observation Observation Observation
                                                                 1    M      26     Papillary Thyroid             Surgery                     Jan-16      Jul-20       55         28       9        Feb-22        3,5          5
                                                                                    Carcinoma
                                                                 2    F      32     Papillary Thyroid             Surgery                     Jan-16     Jan-22        73         24       9       May-22         0            0
                                                                                    Carcinoma
                                                                 3    F      88     Papillary Thyroid             Surgery                     Jan-93     Jun-22        358       28,2      10        n/a          n/a         n/a
                                                                                    Carcinoma
                                                                 4    F      46     Ductal Breast Cancer          Chemotherapy                Jan-08     Feb-20        147        26       10       Jun-22        2            3
                                                                 5    F      66     Ductal Breast Cancer          Surgery                     Jan-16     Mar-22        75         24       10       Jul-22        3            9
                                                                 6    M      74     Prostatic Adenocarcinoma      Surgery                     Dec-16     May-21        54         24       10       Jul-22        0            3
                                                                 7    M      59     Prostatic Adenocarcinoma      Radiotherapy +              May-21     May-22        12         24       8         n/a          n/a         n/a
                                                                                                                  Hormonal therapy
                                                                 8    M      70     Lung Adenocarcinoma           Surgery                     Jan-16     Jan-20        49         24       9        Apr-22        2            4
                                                                 9    M      92     Squamous cell carcinoma       Surgery                     Jun-13     Jun-20        85         26       9       May-22         3            3
                                                                 10   F      74     Ovarian Cancer                Chemotherapy                Jan-09     Jun-20        139        26       9       May-22         2            7
                                                                                                                                                                       Time
                                                                                                                                                                     Between
                                                                                                                                                                      Cancer
                                                                                                                                             Date of     Date of    Diagnosis
                                                                                                                                            Dupilumab   Dupilumab      and                P-NRS                             P-NRS
                                                                                                                                            Treatment   Treatment   Dupilumab   EASI at     at    Date of Last EASI at Last at Last
                                                                 N°   Sex Age            Type of Cancer            Cancer Treatment            Start       Start     (Months)   Baseline Baseline Observation Observation Observation
                                                                 1    M      74     Melanoma                      Surgery                     May-21     Dec-21         7         24       10       Jul-22        0            3
                                                                 2    M      75     Melanoma                      Surgery                     Jun-19     Jan-20         7         27       9        Apr-22        0            0
                                                                 3    M      61     Prostatic Adenocarcinoma      Surgery +                   May-21     May-21         2         25       9        Jul-22        1            1
                                                                                                                  Hormonal Therapy
                                                                 4    M      71     Squamous Cell Carcinoma Surgery                           Jun-19     Jan-20         7         26       10      May-22         0            0




Research Letter | Dermatol Pract Concept. 2023;13(3):e2023143
                                                                EASI = Eczema Area and Severity Index; P-NRS = Pruritus-Numerical Rating Scale.
  the other received dupilumab one year after radiotherapy         dupilumab were cutaneous malignancies. The fourth patient
  and hormonal therapy.                                            was diagnosed with a prostatic adenocarcinoma two months
• One woman had history of ovarian cancer, treated with            after the start of dupilumab: considering his age (61 years
  chemotherapy 11 years before starting dupilumab.                 old) and the short timespan between the diagnosis and the
• One patient underwent pulmonary lobectomy for a lung             start of the treatment, no causal effect could be observed.
  adenocarcinoma 4 years before dupilumab.                         Finally, none of our patients experienced cancer progressions
• One patient was diagnosed with multiple squamous cell            or relapses during treatment.
  carcinomas (SCCs).                                                    We have described a case series of patients with con-
                                                                   comitant malignancies treated with dupilumab. Larger pro-
   All patients are currently undergoing a specific onco-          spective studies with longer follow-up are needed to further
logic follow-up, according to guidelines from the Italian As-      assess this topic. Larger prospective studies with longer
sociation of Medical Oncology. Overall, 4 patients started         follow-up are needed to further assess this topic.
dupilumab less than 5 years after the cancer diagnosis. One
patient received dupilumab one year after completing ra-           References
diotherapy. Six patients have already completed one year of
                                                                   1. Costanzo A, Amerio P, Asero R, et al. Long-term management of
treatment with dupilumab, without any cancer progressions
                                                                      moderate-to-severe adult atopic dermatitis: a consensus by the
or recurrences.
                                                                      Italian Society of Dermatology and Venereology (SIDeMaST),
   Among our patients treated with dupilumab, 4 devel-                the Association of Italian Territorial and Hospital Allergists
oped malignancies during therapy (Table 1). After 7 months            and Immunologists (AAIITO), the Italian Association of Hos-
of therapy, two patients were diagnosed with a melanoma               pital Dermatologists (ADOI), the Italian Society of Allergolog-
in situ and a pT1a melanoma respectively, both completely               ical, Environmental and Occupational Dermatology (SIDAPA),
                                                                        and the Italian Society of Allergy, Asthma and Clinical Immu-
excised. Another patient was diagnosed with a SCC. Another
                                                                        nology (SIAAIC). Ital J Dermatol Venerol. 2022;157(1):1-12.
patient was diagnosed with prostatic carcinoma two months
                                                                        DOI:10.23736/S2784-8671.21.07129-2. PMID: 34929995.
after starting dupilumab; he is currently receiving hormonal       2.   Braddock M, Hanania NA, Sharafkhaneh A, Colice G, Carlsson M.
therapy after prostatectomy. All of these patients never inter-         Potential Risks Related to Modulating Interleukin-13 and
rupted dupilumab and they are still on treatment, complet-              Interleukin-4 Signalling: A Systematic Review. Drug Saf. 2018;
ing one year of follow-up.                                              41(5):489-509. DOI:10.1007/s40264-017-0636-9. PMID: 2941
                                                                        1337. PMCID: PMC5938313.
                                                                   3.   Shirley M. Dupilumab: First Global Approval. Drugs. 2017;
Conclusions                                                             77(10):1115-1121. DOI:10.1007/s40265-017-0768-3. PMID:
                                                                        28547386.
The role of IL-4 and IL-13 in carcinogenesis is still unclear. A   4.   Siliquini N, Giura MT, Viola R, et al. Atopic dermatitis, dupi-
systematic review did not show a higher risk of malignancy              lumab and cancers: a case series. J Eur Acad Dermatol Vene-
                                                                        reol. 2021;35(10):e651-e652. DOI:10.1111/jdv.17264. PMID:
when specifically targeting the IL-13 and IL-4 pathway [2].
                                                                        33797094.
In literature, several case series on patients with concomitant
                                                                   5.   Fowler E, Rosen J, Lev-Tov H, Yosipovitch G. Two Cancer
malignancies have been described, showing no elevated risk              Patients Receiving Dupilumab for Treatment of Atopic Derma-
of cancer recurrences or relapses [4-5]. In our experience,             titis. Acta Derm Venereol. 2019;99(10):899-900. DOI:10.2340
three of the four cancers diagnosed during treatment with               /00015555-3201. PMID: 31037315.




Research Letter | Dermatol Pract Concept. 2023;13(3):e2023143                                                                        3
