Author(s) :
Teodora-Elena Hanea1, Dragoș Goada2, Kiss Anamaria2, Seres Remus2
1 Iuliu Hațieganu University of Medicine and Pharmacy
2 Department of Oncology, Institute of Oncology “Prof dr. Ion Chiricuta” Cluj-Napoca
Corresponding author: Teodora-Elena Hanea, Email: hanea_teodora@yahoo.com
Publication History: Received - , Revised - , Accepted - , Published Online - 29 July 2024.
Copyright: © The author(s). Published by Casa Cărții de Știință.
User License: Creative Commons Attribution – NonCommercial (CC BY-NC)
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Valoarea DOI extrasă din ACF este: 10.53011/JMRO.2024.01.08
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Abstract
Metastatic cutaneous melanomas are treated as a first-line therapy with checkpoint inhibitors, anti-PD-1 antibody, Nivolumab and anti-CTLA-4 antibody, Ipilimumab. Immune-related adverse reactions to immunotherapy include, as the most frequent toxicities, dermatological, gastrointestinal and endocrine toxicity. We present the case of a 51-year-old female, with a medical history of Basedow`s disease and multinodular goitre, who was diagnosed with metastatic cutaneous melanoma in 2019. She underwent surgery of the metastatic lesions, but of an axillary adenopathy which was considered inoperable. She was initially treated with Nivolumab 1mg/kg in combination with Ipilimumab 3mg/kg. Under the double immune checkpoint inhibitors therapy, she developed hepatitis and primary hypothyroidism. Therefore Ipilumamb was discontinued, the patient receiving Nivolumab as monotherapy. Under Nivolumab, the patient developed type 1 diabetes mellitus and primary adrenal insufficiency as further adverse reactions. Despite experiencing multiple endocrinopathies, the patient was allowed to continue the immunotherapy, having a complete response.
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Introduction
Metastatic melanoma, occurring in approximately 15% of cases, presents numerous treatment challenges (1,2). The standard first-line systemic therapy for metastatic or unresectable disease, irrespective of BRAF status, involves immune checkpoint inhibitors (ICIs), such as anti-PD-1 antibodies, with or without anti-CTLA-4 antibodies. Immune-related adverse events (irAEs) are common and dose-dependent, affecting 80%-90% of patients undergoing ICI therapy. Combining these inhibitors increases the risk of significant irAEs, particularly impacting the endocrine, gastrointestinal, hepatic, and dermatologic systems. About 40% of patients experience endocrine toxicities, with the thyroid gland being the most commonly affected organ (3).
While the onset of these adverse effects is unpredictable, they generally appear within six months of starting treatment. The severity of these endocrinopathies varies, and they are rarely fatal. Due to their substantial impact on quality of life and the potential for irreversible effects, early recognition and timely initiation of hormone replacement therapy are essential (4).
2. Case Report
We present the case of a 51-year-old woman with no significant family history and a medical history of multinodular goiter (diagnosed in 2004) and Basedow’s disease (diagnosed in 2018). In 2019, the patient sought medical attention for two suspicious skin lesions, one on the left thigh and the other on the anterior abdominal wall. Both lesions were surgically excised, and the pathological report confirmed cutaneous melanoma, Clark level V, with lymphovascular invasion and a mitotic rate <6/mm², and negative for the BRAF V600E mutation. No adjuvant therapy was recommended. A whole-body 18-FDG PET/CT scan in January 2020 showed no suspicious lesions.
However, a follow-up 18F-FDG PET/CT scan in January 2021 revealed two lesions: one on the right posterior-inferior thoracic wall (9×20 mm, SUVmax=3.8) and another between the left trapezius and supraspinatus muscles (20.3×21.6 mm, SUVmax=8.8). Additionally, left axillary lymphadenopathies (10.5×11.5 mm) were noted (Fig. 1). Ultrasound evaluation detected supraclavicular and axillary adenopathies. The thoracic lesions and the supraclavicular adenopathy were surgically removed, while the left axillary adenopathy was deemed inoperable, resulting in restricted mobility for the patient. Histopathological examination confirmed cutaneous melanoma metastases. The recommended treatment plan included immunotherapy with nivolumab (1 mg/kg) in combination with ipilimumab (3 mg/kg).