Dermatology: Practical and Conceptual Research Letter | Dermatol Pract Concept. 2025;15(1):4967 1 Lichen Planus-Like Exanthema Induced by Anti-PD-1 and Anti-LAG-3 Combination Immunotherapy Could Potentially Predict the Treatment Response in Metastatic Melanoma Marek Pásek1, Eva Sticová2, Emanuel Marques3,4, Vojtěch Tretera1, Petr Arenberger1, Monika Arenbergerová1 1 Department of Dermatology and Venereology, Third Faculty of Medicine, Charles University and Královské Vinohrady University Hospital, Prague, Czech Republic 2 Department of Pathology, Third Faculty of Medicine, Charles University, and Královské Vinohrady University Hospital, Prague, Czech Republic 3 Department of Dermatology and Venereology, St. Joseph Local Health Unit, Lisbon, Portugal 4 Department of Dermatology and Venereology, NOVA Medical School, University Lisbon, Portugal Key words: Melanoma, Anti-PD-1, Anti-LAG-3, Adverse Events Citation: Pásek M, Sticová E, Marques E, Tretera V, Arenberger P, Arenbergerová M. Lichen Planus-Like Exanthema Induced by Anti-PD-1 and Anti-LAG-3 Combination Immunotherapy Could Potentially Predict the Treatment Response in Metastatic Melanoma. Dermatol Pract Concept. 2025;15(1):4967. DOI: https://doi.org/10.5826/dpc.1501a4967 Accepted: November 4, 2024; Published: January 2025 Copyright: ©2024 Pásek 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: Marek Pásek, Srobarova 1150/50, Prague 10, Czech Republic. Phone +420 606 606 346. E-mail: marek.pasek@seznam.cz Introduction A combination therapy using nivolumab (anti-PD-1) and relatlimab (anti-LAG-3) has been compared head-to-head with a monotherapy of nivolumab and shown a statistically significant improvement in progression-free survival rate, with minimal increase in toxicity [1]. Based on these un- precedented results, nivolumab and relatlimab are currently considered the new gold standard in first-line treatment of advanced melanoma [1,2]. Case Presentation A 50-year-old male transferred to our department after a re- section of melanoma lymph node metastasis in the left groin area. We initially performed a whole-body CT scan and MRI of the brain which revealed the involvement of multi- ple lymph nodes in the left groin area and axilla, para-iliac and para-aorta left, in the mediastinum, and under the left clavicle. Furthermore, we performed dermoscopic, otorhino- laryngological, and urological examinations, which did not 2 Research Letter | Dermatol Pract Concept. 2025;15(1):4967 identify any trace of primary melanoma. The testing of the BRAF mutation (BRAF V600E mutated) and initial blood tests (lactate dehydrogenase in the normal range) were per- formed. The conclusive findings confirmed a diagnosis of a metastatic malignant melanoma of unknown primary origin in stage 4A. According to the guidelines, we decided to start first-line of systemic therapy with nivolumab 480 mg and relatlimab 160 mg every 4 weeks [2]. The first 3 infusions re- sulted without any complications. However, after the fourth infusion, an extensive exanthema with pink itchy flat-topped lichenoid papules appeared on the scalp, décolletage, upper third of the back, arms, and thighs (Figure 1, A and B). The mucosa and nail plates were intact. Dermoscopic examina- tion showed Wickham striae, red dots, and radial capillaries [3] (Figure 1C). This immune-mediated adverse event (AE) was evaluated as grade II [4]. A punch biopsy was performed and subsequently, a histological evaluation confirmed the diagnosis of a lichen planus-like exanthema (Figure 1D). Topical therapy with clobetasol propionate, in combination with bilastine 20 mg per day, was initiated, which led to a fast decrease in pruritus. Due to the promising effects of clo- betasole, we decided not to interrupt the oncological treat- ment. On the first re-staging, after 12 weeks of therapy, a partial response was achieved. Conclusions Based on the available data, mainly related to anti-PD-1 +/- anti-CTLA-4 immunotherapy, there appears to be a cor- relation between cutaneous immune-mediated AEs, such as lichen planus-like exanthema etc., and a better prognosis in patients with advanced melanoma [5]. As our case may have shown, it seems that cutaneous AEs do potentially also have the same positive prognostic capabilities in patients with a combination treatment using nivolumab and relatlimab. Ethics Statement: The patient voluntarily signed consent for the publication of the case. Figure 1. (A) Overview of the clinical picture of the lichen planus-like exanthema induced by nivolumab and relatlimab. (B) Clinical presentation of lichenoid papules on the right arm. (C) Dermoscopic picture of lichenoid papules. (D) Histological picture (H&E, magnification ×200). Lichenoid interface dermatitis with patchy lymphocytic infiltrate with some eosinophils and plasma cells in the superficial dermis. Research Letter | Dermatol Pract Concept. 2025;15(1):4967 3 DOI: 10.1136/bcr-2015-213923. PMID: 26759406. PMCID: PMC4716428. 4. National Cancer Institute, National Institutes of Health, US De- partment of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE), ver. 5.0. 2017. Available from: https://ctep.cancer.gov/protocoldevelopment/electronic_ applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf Accessed April 3, 2023. 5. Nikolaou V, Tsimpidakis A, Stratigos A. Cutaneous Adverse Reactions of Immunotherapy in Patients with Advanced Mela- noma. Cancers (Basel). 2023;15(7):2084. DOI: 10.3390/cancers 15072084. PMID: 37046745. PMCID: PMC10093334. References 1. Tawbi HA, Schadendorf D, Lipson EJ, et al. RELATIVITY-047 Investigators. Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma. N Engl J Med. 2022;386(1): 24-34. DOI: 10.1056/NEJMoa2109970. PMID: 34986285. PMCID: PMC9844513. 2. Seth R, Agarwala SS, Messersmith H, et al. Systemic Therapy for Melanoma: ASCO Guideline Update. J Clin Oncol. 2023;41(30): 4794-20. DOI: 10.1200/JCO.23.01136. PMID: 37579248. 3. Litaiem N, Mansour Y, Jones M, et al. Dermoscopic signs of lichen planus. BMJ Case Rep. 2016;2016:bcr2015213923.