Is routine skin examination in metastatic melanoma patients treated with immuno‐ or targeted therapy necessary?

Veld, Eva A. Huis in ’t; Seventer, I.C. van; Teeseling, L. van; Thienen, J.V. van; Crijns, Marianne B.

doi:10.1111/jdv.16128

Cited by 1 publication

(3 citation statements)

References 9 publications

(11 reference statements)

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“…Patients with metastatic melanoma treated with ICIs still risk developing new primary cutaneous melanoma (CMs). 5 For instance, in a cohort of more than 2000 patients with metastatic melanoma treated with ICIs, the incidence of new primary CM was 1.9%, the 5-year cumulative risk was 4.9%, and the incidence rate was 1103 cases per 100,000 person-years. 6 However, new primary CMs occurring during ICI treatment for other malignancies have not been adequately discussed.…”

Section: Introductionmentioning

confidence: 99%

Single-Cell RNA Sequencing Reveals Cellular Heterogeneity in an Acral Amelanotic Melanoma After Immunotherapy Treatment

Liu¹,

Tian²,

Lai³

et al. 2023

CCID

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Background Anti-programmed cell death ligand-1 (anti-PD-L1) immunotherapy is often used for advanced urothelial carcinoma and melanoma, including amelanotic melanoma, a relatively rare subtype with little to no pigment in the tumor cells. However, cellular heterogeneity of amelanotic melanoma during or after anti-PD-L1 immunotherapy treatments has not been described. Purpose To investigate cellular heterogeneity in acral amelanotic melanoma after immunotherapy exposure. Methods We evaluated subtle visual changes of the melanoma by dermoscopy and performed a pathological examination to analyze the heterogeneity of microscopic morphological and immunohistochemistry changes. The cellular transcriptional heterogeneity and corresponding biological function profiles of the melanoma were determined by single-cell RNA sequencing (scRNA-seq). Results The dermoscopic examination revealed black globules and scar-like depigmentation areas against a homogeneous red background. Pigmented and amelanotic melanoma cells were observed microscopically. The pigmented cells were large and contained melanin granules expressing Melan-A and HMB45; the amelanotic cells were small and did not express HMB45. Ki-67 immunohistochemical staining revealed that the pigmented melanoma cells had a higher proliferative ability than the amelanotic cells. scRNA-seq identified three cell clusters: amelanotic cell cluster 1, amelanotic cell cluster 2, and pigmented cell cluster. Furthermore, a pseudo-time trajectory analysis showed that amelanotic cell cluster 2 originated from amelanotic cell cluster 1 and transformed into the pigmented melanoma cell cluster. The expression pattern of melanin synthesis-related and lysosome-endosome-related genes in different cell clusters supported the cell cluster transformation results. Also, upregulated expression of cell cycle genes indicated that the pigmented melanoma cells had a high proliferative ability. Conclusion Coexisting amelanotic and pigmented melanoma cells indicated cellular heterogeneity in an acral amelanotic melanoma from a patient who underwent immunotherapy treatment. Additionally, the pigmented melanoma cells acquired a higher proliferative ability than the amelanotic melanoma cells.

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Section: Introductionmentioning

confidence: 99%

Single-Cell RNA Sequencing Reveals Cellular Heterogeneity in an Acral Amelanotic Melanoma After Immunotherapy Treatment

Liu¹,

Tian²,

Lai³

et al. 2023

CCID

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“…Immune checkpoint inhibitors (ICIs) have been reported to lead to the resolution of unresectable primary cutaneous melanoma (CM), suggesting the potential role for an antitumor effect on synchronous or metachronous CM . A single-center study of 75 patients with metastatic melanoma who responded to systemic treatment identified only 1 patient who developed a new CM . Based on this observation, the authors questioned the utility of routine skin examinations in this patient population.…”

Section: Introductionmentioning

confidence: 99%

“…1 A singlecenter study of 75 patients with metastatic melanoma who responded to systemic treatment identified only 1 patient who developed a new CM. 2 Based on this observation, the authors questioned the utility of routine skin examinations in this patient population. To better inform surveillance guidelines, our objective was to identify the incidence of new CM in patients with metastatic melanoma who received ICIs.…”

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confidence: 99%

Incidence of New Primary Cutaneous Melanoma in Patients With Metastatic Melanoma Treated With Immune Checkpoint Inhibitors

et al. 2021

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IMPORTANCEThe development of new primary cutaneous melanoma (CM) after starting immune checkpoint inhibitor (ICI) therapy is poorly characterized.OBJECTIVE To determine the incidence of new CM in patients treated with ipilimumab, nivolumab, and/or pembrolizumab for metastatic melanoma.DESIGN, SETTING, AND PARTICIPANTS Single-center, retrospective, observational cohort study using an institutional database to identify patients diagnosed with melanoma at a tertiary care cancer hospital in New York, New York.EXPOSURES Ipilimumab, nivolumab, and/or pembrolizumab treatment for metastatic melanoma.MAIN OUTCOMES AND MEASURES Primary outcomes were the incidence proportion, the incidence rate, and the 5-year cause-specific cumulative risk.RESULTS A total of 2251 patients were included in the study; mean (SD) age at the time of ICI start was 62.8 (14.4) years. The majority were male (63.8%, n = 1437), White (92.7%, n = 2086), and non-Hispanic (92.1%, n = 2073). Forty-two of 2251 patients who received ipilimumab, nivolumab, and/or pembrolizumab were diagnosed with 48 new CMs at a median (range) of 397.5 (39-2409) days after ICI initiation. The median age of affected patients at the time of ICI first dose was 66.5 years. The majority were male (66.7%, n = 28), White (92.9%, n = 39), and non-Hispanic (100.0%, n = 42). There were no differences in age, sex, race, and ethnicity among patients who did and did not develop a new CM. Patients who developed a new CM were more likely to have a family history of melanoma (23.8% vs 16.3%, P = .02). Most new CMs (n = 30, 62.5%) were diagnosed after the last date of ICI administration. Twenty-seven (56.3%) new CMs were in situ and 21 (43.8%) were invasive. Of the invasive CMs with a reported Breslow thickness (n = 20), the median (range) thickness was 0.4 (0.1-8.4) mm. The overall incidence proportion of new CM was 1.9% (95% CI, 1.4%-2.5%) and the incidence rate was 1103 cases per 100 000 person-years (95% CI, 815-1492). The 5-year cumulative cause-specific risk of new CM was 4.9% (95% CI, 3.3%-7.4%).CONCLUSIONS AND RELEVANCE Patients treated with ICI therapy for metastatic melanoma remain at risk for the development of new CM.

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Is routine skin examination in metastatic melanoma patients treated with immuno‐ or targeted therapy necessary?

Cited by 1 publication

References 9 publications

Single-Cell RNA Sequencing Reveals Cellular Heterogeneity in an Acral Amelanotic Melanoma After Immunotherapy Treatment

Single-Cell RNA Sequencing Reveals Cellular Heterogeneity in an Acral Amelanotic Melanoma After Immunotherapy Treatment

Incidence of New Primary Cutaneous Melanoma in Patients With Metastatic Melanoma Treated With Immune Checkpoint Inhibitors

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