10.5826/dpc.1303a160
text/xml
2160-9381
3026
en
Zoe Apalla
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
melanoma
Can Cemiplimab Become a Life-Changer in Xeroderma Pigmentosum?
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Research Letter
2023-07-31
2022-11-24
2023-07-31
2023-08-24
e2023160
Dermatol Pract Concept
Zoe Apalla
2023/07/31
10.5826/dpc.1303a160
e2023160
First Department of Dermatology, Aristotle University Thessaloniki, Greece
2160-9381
melanoma
en
e2023160
Momen S, Fassihi H, Davies HR, et al. Dramatic response of metastatic cutaneous angiosarcoma to an immune checkpoint inhibitor in a patient with xeroderma pigmentosum: whole-genome sequencing aids treatment decision in end-stage disease. Cold Spring Harb Mol Case Stud. 2019;5(5):a004408. DOI: 10.1101/mcs.a004408. PMID: 31645345. PMCID: PMC6824248.
Can Cemiplimab Become a Life-Changer in Xeroderma Pigmentosum?
https://dpcj.org/index.php/dpc/article/download/3026/2235
            Can Cemiplimab Become a Life-Changer in
                   Xeroderma Pigmentosum?
   Maria Boziou1, Dimitrios Dionyssiou2, Dimitrios Dionyssopoulos3, Elizabeth Lazaridou1,
                               Aimilios Lallas4, Zoe Apalla1

1 Second Dermatology Department, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
2 Department of Plastic Surgery, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
3 Department of Medical Oncology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
4 First Dermatology Department, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece



Key words: immune checkpoint inhibitors, cemiplimab, xeroderma pigmentosum, squamous cell carcinoma, melanoma
Citation: Boziou M, Dionyssiou D, Dionyssopoulos D, Lazaridou E, Lallas A, Apalla Z. Can Cemiplimab Become a Life-Changer in
Xeroderma Pigmentosum?. Dermatol Pract Concept. 2023;13(3):e2023160. DOI: https://doi.org/10.5826/dpc.1303a160
Accepted: December 9, 2022; Published: July 2023
Copyright: ©2023 Boziou 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: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding author: Maria Boziou, MD, Agiou Pavlou 76, Thessaloniki, Greece tel:+302313323274 E-mail: mariaboziou@gmail.com




Introduction                                                             Case Presentation
Xeroderma Pigmentosum (XP) is a rare inherited autosomal
                                                                         A 29-year-old female with XP was referred to our onco-
recessive disease, resulting in defective repair of the ultravio-
                                                                         dermatology, multidisciplinary unit for management. The pa-
let radiation induced DNA damage. Prognosis of xeroderma
                                                                         tient had undergone numerous surgical excisions in the past.
pigmentosum (XP) is unfavorable, with most patients dying
                                                                         Upon clinical examination, apart from extensive freckling
from metastatic skin cancer before the age of 30.
                                                                         and numerous actinic keratoses, we identified two atypical
    Management is extremely challenging and includes strict
                                                                         melanocytic lesions compatible with melanoma and multiple
avoidance of sun exposure, close monitoring and early thera-
                                                                         basal (BCC) and squamous cell carcinomas (SCC) (Figure 1).
peutic interventions. Cemiplimab is an anti-programmed cell
                                                                         CT scan of chest, upper/lower abdomen and brain MRI were
death 1 (PD-1) antibody, approved for advanced nonmela-
                                                                         unremarkable.
noma Skin Cancers (NMSCs) and tested also for melanoma.
                                                                              We decided to proceed with an “en-bloc” resection of
Taking into account the spectrum of malignancies appearing
                                                                         the skin of the forehead, due to the extreme cancer burden,
in the context of XP, anti-PD-1 antibodies may represent the
                                                                         plus resection of the second atypical melanocytic lesion of
ideal treatment choice [1-8].
                                                                         the lower face. Histologic examination of the forehead skin




Research Letter | Dermatol Pract Concept. 2023;13(3):e2023160                                                                             1
Figure 1. Extreme photodamage, with multiple freckles, two mela-   Figure 2. The patient after 1.5 year of cemiplimab initiation. We ob-
nomas (arrows) and numerous Nonmelanoma Skin Cancers on the        serve complete clinical response, not only of the unresectable squa-
face, including two advanced squamous cell carcinoma, one at the   mous cell carcinoma (SCC) of the right lower eyelid, but also of the
right lower eyelid and one at the right nasolabial fold.           non-resected SCC involving the right nasolabial fold, as well as of
                                                                   the multiple smaller Nonmelanoma Skin Cancers of the facial skin.


showed a fully regressed melanoma, two SCCs and nine               BCCs, coexisting with melanoma. Carrying out a literature
BCCs. The second melanocytic lesion was diagnosed as tu-           review, we retrieved eight individuals with XP treated with
moral melanosis. Breslow thickness could not be defined due        ICIs, with only one of them receiving cemiplimab (Table 1).
to full regression.                                                Overall, as in our patient, individuals receiving ICIs demon-
    A combination of photodynamic therapy(PDT), sequen-            strated a constant response of locally advanced and meta-
tially to 5% imiquimod cream, plus 10mg of daily oral ac-          static tumors of both origins, epithelial and melanocytic.
itretin, as a prophylactic modality, were used. However, the       Tolerability and safety were satisfactory as in our patient.
locally advanced SCC of the eyelid that invaded the conjunc-           The particularity of the current case is the concomitant
tiva posed a serious therapeutic dilemma, since its surgical       presence of unresectable NMSCs and two melanomas, which
removal would inevitably lead to eye loss. Considering the         is a common scenario in the context of XP. ICIs, due to their
limitations of the surgery, the concomitant presence of a sec-     dual therapeutic effect on both, epithelial and melanocytic
ond large SCC involving the right nasolabial fold and the          skin cancers, may open a new therapeutic horizon, changing
overall NMSCs burden in the cancerized areas, we decided           the so far unfavorable fate of XP patients.
to set the patient under treatment with cemiplimab.
    After 1.5 year of systemic treatment with cemiplimab,
there is a remarkable response (Figure 2), with excellent tol-
erance and the treatment is still ongoing.


Conclusions
XP is an ideal model for studying effectiveness of immune
checkpoint inhibitors (ICIs) on skin malignancies, especially
when i0074 comes to the treatment of advanced SCCs and




2                                                                      Research Letter | Dermatol Pract Concept. 2023;13(3):e2023160
                                                                                              Table 1. Outcomes of use of immune checkpoint inhibitors in xeroderma pigmentosum patients
                                                                                                                                                                                             Outcome of
                                                                                      Age/        Tumor                                                                 Outcome of            coexisting        ICI derived       Additional
                                                                    References        Sex      (ICIs target)                Site                      ICI used         target tumor            tumors               AEs           treatment
                                                                Rubatto et al [1]    19/F    Nonoperable,      Right orbital and nasal cavity   Cemiplimab 350 mg     Partial response   Regression of      Diarrhea          Radiotherapy
                                                                                             metastatic SCC    with lymph node metastasis       every 3 weeks                            NMSCs, AK
                                                                Ameri et al [2]      18/F    Nonoperable SCC Limbus of right eye                Pembrolizumab 2 mg/ Complete             No response of     -                 -
                                                                                                                                                kg every 3 weeks    response             facial BCCs
                                                                Ameri, et al [2]     19/M    Nonoperable SCC Right orbital and nasal cavity     Pembrolizumab 2 mg/ Partial response     -                  -                 -
                                                                                                                                                kg every 3 weeks
                                                                Ameri et al [2]      20/F    i)Metastatic      i) MUP                           i)Ipilimumab 10mg/    i)Notable          -                  -                 -
                                                                                             Melanoma          ii) Maxillary sinus              kg every 3 weeks      response
                                                                                             ii) Nonoperable                                    ii) Pembrolizumab     ii) Notable
                                                                                             SCC                                                140mg/month           response till
                                                                                                                                                                      radiographic
                                                                                                                                                                      progression




Research Letter | Dermatol Pract Concept. 2023;13(3):e2023160
                                                                Hauschild et al [3].3 51/M   Metastatic        Left cheek with multiple         Pembrolizumab 2 mg/ 90% regression       Regression         Reddish           -
                                                                                             Melanoma          pulmonary, lymph node and        kg every 3 weeks    of the largest       of almost all      swelling of the
                                                                                                               right infraorbital metastases                        lungmetastasis.      NMSCs, AK          right orbita,
                                                                                                                                                                    Complete                                inflammatory
                                                                                                                                                                    regression of the                       rash in sun-
                                                                                                                                                                    others.                                 damaged skin,
                                                                                                                                                                                                            mild itching
                                                                Deinlein et al [4]   48/F    Metastatic SCC    Left tight with abdominal,       Pembrolizumab 2 mg/ Significant          No                 -                 Metastatic
                                                                                                               inguinal and left                kg every 3 weeks    regression of all    improvement on                       supraclavicular
                                                                                                               supraclavicular lymph node                           metastases           solar lentigines                     lymphadenectomy
                                                                                                               metastases
                                                                Chambon et al [5]    6/F     i)Sarcomatoid     Scalp with bone lytic lesions,   i) Nivolumab 3mg/kg   65% Regression     Appearance of      -                 Chemotherapy
                                                                                             carcinoma         vascular, meningeal contact      every 2 weeks         of the             two invasive                         (5FU, Cisplatin),
                                                                                             ii)SCC            and superior sagittal sinus      ii) Nivolumab         Sarcomatoid        Melanomas on                         surgery
                                                                                                               involvement                      monthly &             carcinoma. No      the scalp.
                                                                                                                                                Cetuximab 250 mg/     response to SCC     Multiple
                                                                                                                                                m2/week, 3 weeks                         cutaneous, lip,
                                                                                                                                                out of 4                                 tongue tumors


                                                                                                                                                                                                                                  Table1 continues




3
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                                                                                             Table 1. Outcomes of use of immune checkpoint inhibitors in xeroderma pigmentosum patients (continued)

                                                                                                                                                                                                       Outcome of
                                                                                         Age/           Tumor                                                                       Outcome of          coexisting          ICI derived       Additional
                                                                     References          Sex         (ICIs target)                   Site                       ICI used           target tumor          tumors                 AEs           treatment
                                                                 Salomon et al [6]     17/M       Metastatic           Scalp with liver and               Pembrolizumab 2 mg/ Partial                Regression of      Vitiligoid     -
                                                                                                  Melanoma             pulmonary metastases               kg every 3 weeks    response of all        NMSCs, AK          depigmentation
                                                                                                                                                                              metastases, long                          on sun-exposed
                                                                                                                                                                              lasting disease                           areas
                                                                                                                                                                              stabilization
                                                                 Steineck et al [7]7   7/F        Metastatic SCC       Right side of the face             Pembrolizumab 2 mg/ Reduction of           Response of        -                 -
                                                                                                                       spreading to the right             kg every 3 weeks    tumor size,            most of the
                                                                                                                       sphenoid bone, the cavernous                           resolution of          oculocutaneous
                                                                                                                       sinus, the right carotid artery,                       leptomeningeal         lesions. Mild
                                                                                                                       the surrounding tissues,                               spread, long           progression of
                                                                                                                       the lymph nodes & the                                  lasting disease        a right corneal
                                                                                                                       leptomeningeal                                         stabilization          SCC
                                                                 Momen et al [8]       32/M       Cutaneous            Left eyebrow with metastatic       Pembrolizumab          Complete          -                    -                 Radiotherapy
                                                                                                  angiosarcoma         pulmonary, pericardial,            200 mg/kg every        response of the
                                                                                                                       mediastinal, pleural,              3 weeks                pulmonary &
                                                                                                                       submandibular, hepatic &                                  bone metastases,
                                                                                                                       bone disease                                              almost complete
                                                                                                                                                                                 response of
                                                                                                                                                                                 the cardiac
                                                                                                                                                                                 & pericardial
                                                                                                                                                                                 disease,
                                                                                                                                                                                 regression of
                                                                                                                                                                                 the hepatic,
                                                                                                                                                                                 submandibular
                                                                                                                                                                                 & pleural lesions

                                                                AEs = adverse events; AK = actinic keratoses; BCC = basal cell carcinoma; F = female; ICI = immune checkpoint inhibitor; M = male; MUP = melanoma of unknown primary; NMSCs = non-melanoma skin
                                                                cancers; SCC = squamous cell carcinoma.




Research Letter | Dermatol Pract Concept. 2023;13(3):e2023160
References                                                            5. Chambon F, Osdoit S, Bagny K, Moro A, Nguyen J, Réguerre Y.
                                                                         Dramatic response to nivolumab in xeroderma pigmentosum
 1. Rubatto M, Merli M, Avallone G, et al. Immunotherapy in Xe-          skin tumor. Pediatr Blood Cancer. 2018;65(2). DOI: 10.1002/
    roderma Pigmentosum: a case of advanced cutaneous squamous           pbc.26837. PMID: 28988442.
    cell carcinoma treated with cemiplimab and a literature review.   6. Salomon G, Maza A, Boulinguez S, et al. Efficacy of anti-
    Oncotarget. 2021;12(11):1116-1121. DOI: 10.18632/oncotar-            programmed cell death-1 immunotherapy for skin carcinomas
    get.27966. PMID: 34084285. PMCID: PMC8169062.                        and melanoma metastases in a patient with xeroderma pigmen-
 2. Ameri AH, Mooradian MJ, Emerick KS, et al. Immunotherapeu-           tosum. Br J Dermatol. 2018;178(5):1199-1203. DOI: 10.1111
    tic strategies for cutaneous squamous cell carcinoma prevention      /bjd.16270. PMID: 29274233.
    in xeroderma pigmentosum. Br J Dermatol. 2019;181(5):1095-        7. Steineck A, Krumm N, Sarthy JF, et al. Response to Pem-
    1097. DOI: 10.1111/bjd.18144. PMID: 31102460.                        brolizumab in a Patient With Xeroderma Pigmentosum and
 3. Hauschild A, Eichstaedt J, Möbus L, et al. Regression of mel-       Advanced Squamous Cell Carcinoma. JCO Precis Oncol.
    anoma metastases and multiple non-melanoma skin cancers in           2019;3:PO.19.00028. DOI: 10.1200/PO.19.00028. PMID:
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Research Letter | Dermatol Pract Concept. 2023;13(3):e2023160                                                                         5
