10.5826/dpc.1301a22
text/xml
2160-9381
2446
en
Jesús Borbujo
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
dermoscopy
Regression of Multiple Melanocytic Nevi in Two Patients on Nivolumab for Metastatic Melanoma
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Research Letter
2023-01-31
2022-03-08
2023-01-31
2023-02-27
e2023022
Dermatol Pract Concept
Jesús Borbujo
2023/01/31
10.5826/dpc.1301a22
e2023022
Department of Dermatology. Hospital Universitario de Fuenlabrada, Madrid, Spain
2160-9381
dermoscopy
en
e2023022
Lallas A, Apalla Z, Kyrgidis A, et al. Second primary melanomas in a cohort of 977 melanoma patients within the first 5 years of monitoring. J Am Acad Dermatol. 2020;82(2):398-406. DOI:10.1016/j.jaad.2019.08.074. PMID: 31499156.
Regression of Multiple Melanocytic Nevi in Two Patients on Nivolumab for Metastatic Melanoma
https://dpcj.org/index.php/dpc/article/download/2446/1909
    Regression of Multiple Melanocytic Nevi in Two
    Patients on Nivolumab for Metastatic Melanoma
       Gloria Baeza-Hernández1, Ricardo Francisco Rubio-Aguilera1, Anastasia Alejandra
       Garrido-Ríos1, Helena Álvarez-Garrido1, Cristina Martínez-Morán1, Jesús Borbujo1


1 Department of Dermatology. Hospital Universitario de Fuenlabrada, Madrid, Spain



Key words: nivolumab, regression, melanocytic nevi, melanoma, dermoscopy
Citation: Baeza- Hernández G, Rubio-Aguilera RF, Garrido-Ríos AA, Álvarez-Garrido H, Martínez-Morán C, Borbujo J. Regression Of
Multiple Melanocytic Nevi In Two Patients On Nivolumab For Metastatic Melanoma. Dermatol Pract Concept. 2023;13(1):e2023022.
DOI: https://doi.org/10.5826/dpc.1301a22
Accepted: May 26, 2022; Published: January 2023
Copyright: ©2023 Baeza- Hernández 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: Gloria Baeza-Hernández, Servicio de Dermatología, Hospital de Fuenlabrada, Camino del Molino 2, 28942
Fuenlabrada, Madrid. E-mail: gloria.baeza@salud.madrid.org




Introduction                                                             aware of any changes or new melanocytic lesions. On phys-
                                                                         ical examination, no new lesions were detected since their
Immunotherapy (anti-PD1 and anti-CTLA4) has been de-                     last visit one year before; with dermoscopy several of their
scribed to achieve complete regression of non-metastatic                 benign melanocytic nevi had lightened and no atypical or
melanoma, assessed by reflectance confocal microscopy;                   malignant lesions were observed (Figures 1 and 2). Both pa-
however, their effects on benign melanocytic lesions have                tients had experienced disease progression despite anti-PD1
not been thoroughly studied and may be underreported [1].                treatment.
Herein we report 2 patients with regression of multiple
nevi while on treatment with nivolumab for metastatic
                                                                         Conclusions
melanoma.
                                                                         Benign melanocytic nevi regression is an emerging sec-
                                                                         ondary effect of anti-PD1 drugs nivolumab and pembroli-
Case Presentation
                                                                         zumab. Although these drugs are used on other cancer
Two patients, suffering from metastatic melanoma treated                 treatments, this secondary effect seems to be more frequent
with nivolumab (Table 1), attended our outpatient clinic for             in patients undergoing treatment for melanoma [2]. In an
their annual digital dermoscopic monitoring. They were not               observational study published in 2017, 11 patients treated




Research Letter | Dermatol Pract Concept. 2023;13(1):e2023022                                                                         1
                                              Table 1. Patient characteristics.
         Metastatic melanoma                          Patient 1                                        Patient 2
 Sex                                     Male                                     Male
 Age, years                              50                                       60
 Location                                Abdomen                                  Back
 Mutation                                BRAF V600E/E2/D
 Treatment before/after nivolumab        Before: dabrafenib-trametinib,           No
                                         which was stopped because
                                         metastases spread to his lungs
                                         and inguinal and retroperitoneal
                                         lymph nodes (lymphadenectomy
                                         was performed)
 Nivolumab start and end dates/doses 2021 – ongoing/                              2020-2021/
 mg/weeks                            240 mg every 2 weeks                         480 mg every 4 weeks
 Lightening of nevi observed with        2021: > 80% of his nevi.                 2022: > 60% of his nevi.
 digital dermoscopy                      (Previous digital monitoring:            (Previous digital monitoring: 2021)
                                         2020)
 Nivolumab secondary effects             Yes, vitiligo-like lesions               Yes, nivolumab-induced thyrotoxicosis and
                                                                                  subsequent hypothyroidism
 Disease progression while on            Yes, new lymph node metastases           Yes, dermal melanoma metastases on the back
 nivolumab                               near his melanoma scar on                (2021)
                                         the abdomen and small bowel
                                         metastases (2022)
 Second melanoma while on                Yes, melanoma in situ on his             Yes, melanoma on his right leg (Breslow
 treatment                               back while on dabrafenib-                thickness 3.4 mm) while on nivolumab (2021).
                                         trametinib (2020).
                                         Both were detected in the annual digital dermoscopy monitoring visit.
 Other                                   -                                        A lung adenocarcinoma was diagnosed while
                                                                                  on nivolumab (2021) and later excised. He has
                                                                                  developed mediastinal lymph node metastases,
                                                                                  awaiting treatment.




with anti-PD1 for metastatic melanoma (10 with pembroli-              progression despite nivolumab treatment; therefore, more
zumab and 1 with nivolumab) had more lightened nevi                   studies are required to shed light on this matter [2,5,7].
than controls during follow-up (49% versus 19%); nev-                 One of our patients also had vitiligo-like phenomenon,
ertheless, differences were not statistically significant [3].        which has been suggested to be associated with a better
Lightening without halo is a known phenomenon, espe-                  prognosis [2].
cially in patients treated with pembrolizumab [4,5]. There               Furthermore, some other questions remain still unan-
are few reports regarding regression of melanocytic nevi in           swered: it could be asked why some patients experience
patients treated with nivolumab: one similar to our patient,          only lightening without halo, while others have vitiligo-like
with no inflammation or halo, and another patient who                 reactions and halo nevi, and whether the underlying mech-
experimented inflammation before regression, with no halo             anism is the same [3]; why some patients have clinical
[6,7]. Though some articles suggest that regression of mela-          inflammation but most of them do not according to the
nocytic nevi may be related to the therapeutic effect of the          literature. Lastly, it is debatable whether regression of nevi
anti-PD1 drug and could be interpreted as a sign of good              with anti-PD1 is as rare as it seems today, for it may be an
therapeutical response, our patients both experimented                unnoticed secondary effect in other cancer patients (lung,




2                                                                         Research Letter | Dermatol Pract Concept. 2023;13(1):e2023022
Figure 1. Clinical images of patient 1: 2020 (left) and 2021 (right). Three examples of lesions registered in digital monitoring of patient 1.
(A1-C1) First row shows these benign melanocytic in 2020. (A2-C2) Second row shows the same lesions one year later in 2021, 6 months
after starting treatment with nivolumab.




kidney, head, and neck, etc.) who are not followed up in a               melanomas detected during surveillance were in situ [9]. We
dermatology clinic.                                                      think that, when available and feasible, monitoring with
    One may well wonder about the utility of digital mon-                digital dermoscopy and total body photography should be
itoring of patients with metastatic melanoma undergoing                  offered to all melanoma patients, as it helps in the early diag-
treatment with immune checkpoint inhibitors (ICI). In a                  nosis of melanoma, with some lesions being only diagnosed
recent single-center retrospective cohort study 42 patients              by dermoscopic changes in the absence of melanoma-specific
(1.9%) with metastatic melanoma who received treatment                   criteria [9].
with ICI developed new melanomas; thus, prospective stud-                    Regression of multiple nevi is a scarcely reported second-
ies with longer follow-up are needed to draw a solid con-                ary effect of nivolumab we should be aware of, especially in
clusion [8]. While on ICI, both of our patients had a second             dermoscopic monitoring. It may be an overlooked effect be-
melanoma that was detected in the digital follow-up; we                  cause patients treated with anti-PD1 for cancers other than
want to highlight that in case 1, with longer digital moni-              melanoma are not usually examined by a dermatologist. Its
toring, melanoma was detected in situ, in line with the find-            prognostic meaning is still unclear.
ings of Lallas et al where almost 70% of second primary




Research Letter | Dermatol Pract Concept. 2023;13(1):e2023022                                                                               3
Figure 2. Clinical images of patient 2: 2021 (left) and 2022 (right). Three lesions registered in digital monitoring of patient 2. (D1-F1) First
row shows these benign melanocytic nevi in 2021, while on nivolumab treatment. (D2-F2) Second row displays the same lesions one year
later in 2022, 6 months after finishing treatment with nivolumab.




References                                                                 4. Wolner ZJ, Marghoob AA, Pulitzer MP, Postow MA, Marchetti
                                                                              MA. A case report of disappearing pigmented skin lesions asso-
 1. Navarrete-Dechent C, Cordova M, Postow MA, et al. Eval-                   ciated with pembrolizumab treatment for metastatic melanoma.
    uation of the Response of Unresectable Primary Cutaneous                  Br J Dermatol. 2018;178(1):265-269. DOI:10.1111/bjd.15354.
    Melanoma to Immunotherapy Visualized With Reflectance                     PMID: 28132411. PMCID: PMC5533648.
    Confocal Microscopy. JAMA Dermatology. 2019;155(3):347.                5. Mauzo SH, Tetzlaff MT, Nelson K, et al. Regressed melanocytic
    DOI:10.1001/jamadermatol.2018.3688. PMID: 30624578. PM-                   nevi secondary to pembrolizumab therapy: an emerging mela-
    CID: PMC6440283.                                                          nocytic dermatologic effect from immune checkpoint antibody
 2. Farinazzo E, Zelin E, Agozzino M, et al. Regression of nevi,              blockade. Int J Dermatol. 2019;58(9):1045-1052. DOI:10.1111
    vitiligo-like depigmentation and halo phenomenon may indi-                /ijd.13833. PMID: 29152725.
    cate response to immunotherapy and targeted therapy in mel-            6. Vazquez B, Velasco R, Martin JM, Gonzalez I, Ramon MD.
    anoma. Melanoma Res. 2021;31(6):582-585. DOI:10.1097                      Regression of multiple melanocytic nevi associated with
    /CMR.0000000000000776. PMID: 34433200.                                    nivolumab treatment for metastatic melanoma. Int J Dermatol.
 3. Zhao CY, Hwang SJE, Wakade D, Carlos G, Anforth R,                        2019;58(11):1331-1333. DOI:10.1111/ijd.14340. PMID: 30536371.
    Fernández-Peñas P. Melanocytic lesion evolution patterns with          7. Nakamura Y, Fujino T, Kagamu H, et al. Induction of immune re-
    targeted therapies and immunotherapies for advanced met-                  action in benign melanocytic nevi without halo during nivolumab
    astatic melanoma: An observational study. Australas J Der-                therapy in a patient with melanoma. JAMA Dermatology.
    matol. 2017;58(4):292-298. DOI:10.1111/ajd.12645. PMID:                   2017;153(8):832-834. DOI:10.1001/jamadermatol.2017.0615.
    28707403.                                                                 PMID: 28492864.




4                                                                             Research Letter | Dermatol Pract Concept. 2023;13(1):e2023022
 8. Nanda JK, Dusza SW, Navarrete-Dechent C, Liopyris K, Marghoob   9. Lallas A, Apalla Z, Kyrgidis A, et al. Second primary melanomas
    AA, Marchetti MA. Incidence of New Primary Cutaneous Mela-         in a cohort of 977 melanoma patients within the first 5 years
    noma in Patients With Metastatic Melanoma Treated With Immune      of monitoring. J Am Acad Dermatol. 2020;82(2):398-406.
    Checkpoint Inhibitors. JAMA Dermatology. 2021;157(1):79.           DOI:10.1016/j.jaad.2019.08.074. PMID: 31499156.
    DOI:10.1001/jamadermatol.2020.3671. PMID: 32936222.
    PMCID: PMC7495326.




Research Letter | Dermatol Pract Concept. 2023;13(1):e2023022                                                                       5
