Diphencyprone as a therapeutic option in cutaneous metastasis of melanoma. A single-institution experience

Gibbons, Ivana Lameiras; Sonagli, Marina; Bertolli, Eduardo; Macedo, Mariana Petaccia de; Pinto, Clóvis Antônio Lopes; Neto, João Pedreira Duprat

doi:10.1590/abd1806-4841.20187162

Cited by 10 publications

(4 citation statements)

References 10 publications

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“…The response to DPCP and the survival rates are in keeping with the results published by the current group, 7 two Australian cohorts, 5,6 and two smaller Canadian and Brazilian cohorts. 24,25 Collation of the published data for 192 patients to date shows that DPCP has an overall response (CR ? PR) rate of 64.6%.…”

Section: Discussionmentioning

confidence: 99%

Quantitative and Spatial Analysis of CD8+/PD-1 Tumor-Infiltrating Lymphocytes as a Predictive Biomarker for Clinical Response of Melanoma In-Transit Metastases to Topical Immunotherapy

et al. 2020

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Background Melanoma in-transit metastases (ITMs) are a challenge to treat and associated with systemic disease and poor prognosis. Topical diphencyprone (DPCP), a potent contact sensitizer, is an established treatment for melanoma ITMs. This exploratory study investigated the utility of BRAF mutation status, CD8, PD-1, PD-L1, and TILs distribution as biomarkers for response of ITMs to topical immunotherapy (DPCP). Methods The ITM deposits of 40 patients treated with DPCP were subjected to biomarker analysis for BRAF status, CD8 and PD-1 expression on tumor-infiltrating lymphocytes (TILs), and tumor PD-L1 expression. Response to DPCP and overall survival (OS) were compared by biomarker status. Results After 12 weeks, 10 patients (25%) had a complete response, 12 patients (30%) had a partial response, and 18 patients (45%) had no response. No significant association was found between any individual biomarker and response to DPCP or OS. The BRAF mutation rate was 25% (10/40). All the patients with a complete response had BRAF wild-type tumor. Peritumoral CD8+ T-cells were associated with complete response ( P = 0.041). Both CD8+ and PD-1 expressions were highly correlated ( P < 0.0001), and the highest levels of PD-1 expression were detected at the peritumoral interface ( P = 0.0004). Only two cases were PD-L1-positive, and both had a complete response to DPCP ( P = 0.043). Conclusion Patients who have BRAF wild-type tumor are more likely to experience a complete response to DPCP. Peritumoral TILs and PD-1 expressions may predict a better response to DPCP. Expression of PD-L1 may be associated with a complete response to DPCP. A larger prospective study is required.

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Section: Discussionmentioning

confidence: 99%

Quantitative and Spatial Analysis of CD8+/PD-1 Tumor-Infiltrating Lymphocytes as a Predictive Biomarker for Clinical Response of Melanoma In-Transit Metastases to Topical Immunotherapy

et al. 2020

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“…A Brazilian study showed that diphencyprone can lead to up to 37% of complete response in cases of cutaneous melanoma metastases. 62 …”

Section: Treatmentmentioning

confidence: 99%

Cutaneous metastases from solid neoplasms – Literature review

Souza

Miyashiro

Pincelli

et al. 2023

Anais Brasileiros de Dermatologia

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“…Topical immunotherapy in the form of contact sensitizers, such as diphencyprone (DPCP), has demonstrated at least partial cutaneous melanoma metastasis regression in up to 84% of patients across multiple studies 3 , 4 . In some cases, further disease progression still occurs despite treatment with contact sensitizer monotherapy.…”

Section: Introductionmentioning

confidence: 99%

Proteomic profiling of a patient with cutaneous melanoma metastasis regression following topical contact sensitizer diphencyprone and immune checkpoint inhibitor treatment

Han

Agarwal

Young

et al. 2022

Sci Rep

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Immune checkpoint inhibitors (ICIs) such as pembrolizumab have revolutionized the treatment of advanced melanoma, but many patients do not respond to ICIs alone, and thus there is need for additional treatment options. Topical immunomodulators such as diphencyprone (DPCP) also have clinical use in advanced melanoma, particularly in the treatment of cutaneous metastases. In a previous report, we characterized the enhanced clinical response to dual agent immunotherapy with pembrolizumab and DPCP in a patient with cutaneous melanoma metastases. To improve mechanistic understanding of this response, we analyzed proteomic data using the Olink immuno-oncology panel of 96 biomarkers from tissue and serum samples of this patient throughout his treatment course. Particular attention was paid to programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and lymphocyte-activation gene 3 (LAG-3) given they are all targeted by ICIs in clinical practice. These proteins were upregulated during the period of DPCP monotherapy, then downregulated during pembrolizumab monotherapy, and then robustly upregulated again during dual therapy. Although not exclusively, the induction of checkpoint inhibitor proteins in the presence of DPCP suggests potential synergy between this agent and ICIs in the treatment of cutaneous melanoma metastases. Large-scale investigation is warranted to further evaluate this potential novel combination therapeutic approach.

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Diphencyprone as a therapeutic option in cutaneous metastasis of melanoma. A single-institution experience

Cited by 10 publications

References 10 publications

Quantitative and Spatial Analysis of CD8+/PD-1 Tumor-Infiltrating Lymphocytes as a Predictive Biomarker for Clinical Response of Melanoma In-Transit Metastases to Topical Immunotherapy

Quantitative and Spatial Analysis of CD8+/PD-1 Tumor-Infiltrating Lymphocytes as a Predictive Biomarker for Clinical Response of Melanoma In-Transit Metastases to Topical Immunotherapy

Cutaneous metastases from solid neoplasms – Literature review

Proteomic profiling of a patient with cutaneous melanoma metastasis regression following topical contact sensitizer diphencyprone and immune checkpoint inhibitor treatment

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