Dimitriou Florentia, Orloff Marlana M, Koch Hein Erica C, Cheng Phil F, Hughes Isaac F, Simeone Ester, Montazeri Kamaneh, Grover Piyush, Mehmi Inderjit, Gerard Camille L, Gaudy-Marqueste Caroline, Grob Jean-Jacques, Michielin Olivier, Hamid Omid, Long Georgina V, Sullivan Ryan, Kapiteijn Ellen, Johnson Douglas B, Ascierto Paolo A, Joshua Anthony M, Carvajal Richard D, Butler Marcus O, Hassel Jessica C, Dummer Reinhard
Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland; Faculty of Medicine, University of Zurich, Zurich, Switzerland.
Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Eur J Cancer. 2025 Jan;214:115161. doi: 10.1016/j.ejca.2024.115161. Epub 2024 Nov 30.
BACKGROUND: Metastatic uveal melanoma (mUM) is rare. Immune checkpoint inhibitors (ICIs) have shown modest efficacy in mUM. Tebentafusp prolonged overall survival (OS) in a phase 3 study. We aimed to investigate the efficacy and safety of the sequence of tebentafusp and ICIs. METHODS: Patients with HLA-A * 02:01 positive mUM, or metastatic GNA11/GNAQ mutant melanocytic tumors treated with tebentafusp followed by ICIs (group 1) or the inverse sequence (group 2) at any treatment line were retrospectively identified. The primary objective was OS rate at 2 years. RESULTS: 131 patients were included; 51 in group 1 and 80 in group 2. 30 % in group 1 % and 40 % in group 2 had normal baseline lactate dehydrogenase (LDH, p = 0.05). 94 % in group 1 % and 77 % in group 2 had multilobular liver disease (p = 0.02). Median OS was 22.4 months (95 % CI 19-24.8) in group 1 and 33.6 months (95 % CI 28.9-43) in group 2 (p = 0.004). Total median PFS was 12 months (95 % CI 10.7-18.8) in group 1 and 20.3 months (95 % CI 17.2-27.3) in group 2 (p = 0.04). The frequency of cytokine release syndrome was higher in group 2 (15 % vs 27 %). Other clinical factors were associated with short total PFS in the multivariable analysis. CONCLUSIONS: Both treatment sequences are clinically feasible. A clinical benefit was noted in the sequential combination of ICIs followed by tebentafusp. This observation is limited by the retrospective nature of the study and merits further investigation in prospective clinical trials.
背景：转移性葡萄膜黑色素瘤（mUM）较为罕见。免疫检查点抑制剂（ICIs）在mUM中显示出一定疗效。替本妥昔单抗在一项3期研究中延长了总生存期（OS）。我们旨在研究替本妥昔单抗与ICIs序贯治疗的疗效和安全性。 方法：回顾性纳入在任何治疗线接受替本妥昔单抗治疗后再接受ICIs治疗（第1组）或相反顺序治疗（第2组）的HLA-A * 02:01阳性mUM患者，或转移性GNA11/GNAQ突变黑素细胞肿瘤患者。主要目标是2年时的OS率。 结果：共纳入131例患者；第1组51例，第2组80例。第1组30%和第2组40%的患者基线乳酸脱氢酶（LDH）正常（p = 0.05）。第1组94%和第2组77%的患者有多叶性肝病（p = 0.02）。第1组的中位OS为22.4个月（95%CI 19 - 24.8），第2组为33.6个月（95%CI 28.9 - 43）（p = 0.004）。第1组的总中位无进展生存期（PFS）为12个月（95%CI 10.7 - 18.8），第2组为20.3个月（95%CI 17.2 - 27.3）（p = 0.04）。第2组细胞因子释放综合征的发生率更高（15%对27%）。多变量分析中，其他临床因素与总PFS短相关。 结论：两种治疗顺序在临床上均可行。ICIs序贯替本妥昔单抗治疗显示出临床获益。本观察受研究的回顾性性质限制，值得在前瞻性临床试验中进一步研究。
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