Reinhard Sören, Utikal Jochen Sven, Zaremba Anne, Lodde Georg, von Wasielewski Imke, Klespe Kai Christian, Meier Friedegund, Haferkamp Sebastian, Kähler Katharina C, Herbst Rudolf, Gebhardt Christoffer, Sindrilaru Anca, Dippel Edgar, Angela Yenny, Mohr Peter, Pfoehler Claudia, Forschner Andrea, Kaatz Martin, Schell Beatrice, Gesierich Anja, Loquai Carmen, Hassel Jessica C, Ulrich Jens, Meiss Frank, Schley Gaston, Heinzerling Lucie M, Sachse Michael, Welzel Julia, Weishaupt Carsten, Sunderkötter Cord, Michl Christiane, Lindhof Harm-Henning, Kreuter Alexander, Heppt Markus V, Wenk Saskia, Mauch Cornelia, Berking Carola, Nedwed Annekathrin Silvia, Gutzmer Ralf, Leiter Ulrike, Schadendorf Dirk, Ugurel Selma, Weichenthal Michael, Haist Maximilian, Fleischer Maria Isabel, Lang Berenice, Grabbe Stephan, Stege Henner
Department of Dermatology, University Medical Center Mainz, Mainz 55131, Germany.
Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.
Eur J Cancer. 2025 May 2;220:115356. doi: 10.1016/j.ejca.2025.115356. Epub 2025 Mar 15.
Melanoma is the main cause of skin cancer-related death. Treatment with immune checkpoint inhibitors (CPI) has improved the prognosis in recent years. However, subtypes of melanoma differ in their response. Acral lentiginous melanoma (ALM) has a worse prognosis compared to cutaneous melanoma other than ALM (CM) and is therefore of particular relevance.
To evaluate the efficacy of CPI in first-line treatment of patients with advanced ALM compared CM.
Retrospective analysis of patients with metastatic ALM (n = 45) or CM (n = 328) who received first-line CPI therapy from the multicenter prospective skin cancer registry ADOREG. Study endpoints were best overall response (BOR), progression-free survival (PFS) and overall survival (OS).
ALM patients had significantly higher rates of ulcerated tumors, loco regional metastases and fewer BRAF-mutated tumors compared to CM patients. Combined CPI was administered in 48.9 % ALM patients and 39.3 % of CM patients, while the remaining patients received PD-1 monotherapy. OS trended to be shorter in patients with ALM (18.1 vs. 43.8 months, p = 0.10) with no significant differences in PFS (7.0 vs. 11.5 months, p = 0.21). In patients with CM, median OS with combined CPI was not reached, whereas the median OS after PD-1 monotherapy was 37.8 months (p = 0.22). Conversely, in patients with ALM, OS with combined CPI was 17.8 months, compared to 26 months with PD-1 monotherapy (p = 0.15). There were no significant differences in BOR between patients with ALM or CM.
Analysis of this real-world cohort of patients with metastatic melanoma showed a trend towards poorer survival outcomes upon first-line treatment with CPI in ALM compared to cutaneous melanoma of other subtypes.
黑色素瘤是皮肤癌相关死亡的主要原因。近年来，免疫检查点抑制剂（CPI）治疗改善了预后。然而，黑色素瘤的亚型对治疗的反应有所不同。肢端雀斑样痣黑色素瘤（ALM）与非ALM皮肤黑色素瘤（CM）相比，预后更差，因此具有特殊意义。
评估CPI一线治疗晚期ALM患者与CM患者相比的疗效。
对多中心前瞻性皮肤癌登记处ADOREG中接受一线CPI治疗的转移性ALM患者（n = 45）或CM患者（n = 328）进行回顾性分析。研究终点为最佳总体缓解（BOR）、无进展生存期（PFS）和总生存期（OS）。
与CM患者相比，ALM患者溃疡肿瘤、局部区域转移的发生率显著更高，BRAF突变肿瘤更少。48.9%的ALM患者和39.3%的CM患者接受了联合CPI治疗，其余患者接受PD - 1单药治疗。ALM患者的OS有缩短趋势（18.1个月对43.8个月，p = 0.10），PFS无显著差异（7.0个月对11.5个月，p = 0.21）。在CM患者中，联合CPI治疗的中位OS未达到，而PD - 1单药治疗后的中位OS为37.8个月（p = 0.22）。相反，在ALM患者中，联合CPI治疗的OS为17.8个月，而PD - 1单药治疗为26个月（p = 0.15）。ALM或CM患者之间的BOR无显著差异。
对这一转移性黑色素瘤患者的真实世界队列分析显示，与其他亚型的皮肤黑色素瘤相比，ALM患者一线使用CPI治疗后的生存结局有较差的趋势。
