Mihaila Raluca Ioana, Gheorghe Adelina Silvana, Zob Daniela Luminita, Stanculeanu Dana Lucia
Department of Oncology, University of Medicine and Pharmacy Bucharest, Bucharest, ROU.
Department of Medical Oncology I, Institute of Oncology "Prof. Dr. Alexandru Trestioreanu", Bucharest, ROU.
Cureus. 2024 Sep 12;16(9):e69301. doi: 10.7759/cureus.69301. eCollection 2024 Sep.
Cutaneous malignant melanoma is one of the most aggressive forms of skin cancer and thus, a high mortality has been reported over decades. The prognosis for melanoma varies widely based on several factors, including the stage at which it is diagnosed, the location and thickness of the tumor, the patient's age and overall health, and specific genetic factors associated with melanoma. Therapeutic options include checkpoint inhibitors, regardless of V-Raf Murine Sarcoma Viral Oncogene Homolog B status (BRAF), and targeted therapy (anti-BRAF) in the adjuvant or metastatic setting. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but predicting which patients will benefit from these therapies remains challenging. Biomarkers like leukocytes, neutrophils, eosinophils, basophils, platelets, and other peripheral blood biomarkers have been investigated for their potential to predict responses to ICIs. Tumor mutational burden (TMB), circulating tumor DNA (ctDNA), and soluble PD-L1 (sPD-L1) have emerged as potential biomarkers for predicting responses to ICIs. Elevated baseline levels of ctDNA and elevated sPD-L1 levels have been associated with worse prognosis in melanoma patients. High TMB is often associated with better responses to ICIs in melanoma. Here we present a case from our department, of a 57-year-old patient, diagnosed in 2019 with stage IV - pT4cNx cM1 (lymph nodes metastases) and suspicion of lung metastases, BRAF wild-type right hallux malignant melanoma. Due to impressive results, first-line treatment with ICIs nivolumab and ipilimumab was the preferred treatment of choice, which showed a favorable response, with regression of oncological disease after the first cycle, and achieving complete response afterward. Unfortunately, the treatment was discontinued due to severe hepatic and pancreatic toxicity, but the favorable response to immunotherapy has been maintained for four years and is ongoing. Identifying predictive biomarkers is important to achieve the best response for the patient, with minimal adverse events, especially if long-term clinical benefit can be reached.
皮肤恶性黑色素瘤是最具侵袭性的皮肤癌形式之一，因此，数十年来报告的死亡率一直很高。黑色素瘤的预后因多种因素而有很大差异，包括诊断时的分期、肿瘤的位置和厚度、患者的年龄和整体健康状况，以及与黑色素瘤相关的特定遗传因素。治疗选择包括检查点抑制剂，无论V-Raf鼠肉瘤病毒癌基因同源物B（BRAF）状态如何，以及在辅助或转移情况下的靶向治疗（抗BRAF）。免疫检查点抑制剂（ICI）彻底改变了癌症治疗，但预测哪些患者将从这些治疗中获益仍然具有挑战性。已经研究了白细胞、中性粒细胞、嗜酸性粒细胞、嗜碱性粒细胞、血小板和其他外周血生物标志物等生物标志物预测对ICI反应的潜力。肿瘤突变负荷（TMB）、循环肿瘤DNA（ctDNA）和可溶性程序性死亡受体配体1（sPD-L1）已成为预测对ICI反应的潜在生物标志物。ctDNA基线水平升高和sPD-L1水平升高与黑色素瘤患者的预后较差有关。高TMB通常与黑色素瘤患者对ICI的更好反应相关。在此，我们介绍我们科室的一个病例，一名57岁患者，于2019年被诊断为IV期-pT4cNx cM1（淋巴结转移），怀疑有肺转移，BRAF野生型右拇趾恶性黑色素瘤。由于效果显著，一线使用ICI纳武单抗和伊匹木单抗治疗是首选治疗方案，该方案显示出良好的反应，在第一个周期后肿瘤性疾病消退，并随后实现完全缓解。不幸的是，由于严重的肝脏和胰腺毒性，治疗中断，但对免疫治疗的良好反应已维持四年且仍在持续。确定预测性生物标志物对于使患者获得最佳反应、将不良事件降至最低非常重要，特别是如果能够实现长期临床获益。
