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晚期黑色素瘤患者的分子分析和匹配的向治疗:MatchMEL研究第1部分的结果

Andrea Boutros^1,2, Matteo S Carlino^1,3, Raja Chaganti³

¹Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.

JCO precision oncology

|March 12, 2026

概括

患有NF1突变的晚期黑色素瘤患者表现出更高的瘤突变负担和更好的免疫检查点抑制剂 (ICI) 反应. 这一发现突出了BRAF/NRAS野生型黑色素瘤的潜在治疗点.

科学领域:

在瘤学瘤学.
基因组学就是基因组学.
免疫治疗是一种免疫疗法.

背景情况:

确立了BRAF/NRAS突变黑色素瘤的临床病理特征.
接受免疫检查点抑制剂 (ICI) 的BRAF/NRAS野生类型 (WT) 黑色素瘤患者的分子概况和治疗结果需要进一步阐明.
MatchMEL研究旨在解决这些知识差距.

研究的目的:

为了研究BRAF/NRAS WT晚期黑色素瘤的基因组景观.
为了确定ICI治疗的患者的临床病理特征和分子变化.
为了将分子发现与治疗反应和生存结果相关联.

主要方法:

在澳大利亚两个中心招募了210名患有晚期黑色素瘤的患者.
在BRAF/NRAS WT患者中进行了FoundationOneCDx (F1CDx) 测序.
分析了瘤突变负担 (TMB),整体响应率 (ORR) 和无进展生存率 (PFS) 之间的关联,使用后勤回归和卡普兰-梅尔方法.

主要成果:

在队列中确定了100名 (48%) BRAF/NRAS WT患者.
在37名WT患者中检测到NF1突变 (43%),与最高的中位数TMB (53mut/Mb) 相关.
与其他亚型相比,NF1-突变黑色素瘤的PFS中位数比较长 (26.8个月),ORR (63%) 对一线ICI比较高.

结论:

在接受ICI治疗的晚期黑色素瘤患者中存在显著的临床,病理和分子相关性.
黑色素瘤中的NF1突变与TMB的增加有关.
与NF1突变相关的较高TMB与ICI反应的改善相关.

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