DePalo Danielle K, Dugan Michelle M, Naqvi Syeda Mahrukh Hussnain, Ollila David W, Hieken Tina J, Block Matthew S, van Houdt Winan J, Wouters Michel W J M, Reijers Sophie J M, Asher Nethanel, Broman Kristy K, Duncan Zoey, Anderson Matilda, Gyorki David E, Snow Hayden, Held Jenny, Farma Jeffrey M, Vetto John T, Hui Jane Y C, Kolbow Madison, Saw Robyn P M, Lo Serigne N, Long Georgina V, Thompson John F, Kim Youngchul, Karapetyan Lilit, Ny Lars, van Akkooi Alexander C J, Olofsson Bagge Roger, Zager Jonathan S
Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, Florida, USA.
University of North Carolina, Chapel Hill, North Carolina, USA.
Cancer. 2025 Jan 1;131(1):e35636. doi: 10.1002/cncr.35636. Epub 2024 Nov 10.
BACKGROUND: Isolated limb infusion and perfusion (ILI/ILP) has been a mainstay treatment for unresectable melanoma in-transit metastases (ITM), but increased use of immune checkpoint inhibitors (ICI) and intralesional therapy (talimogene laherparepvec [TVEC]) introduced several different management options. This study compares first-line ILI/ILP, ICI, and TVEC. METHODS: Retrospective review from 12 international institutions included patients treated from 1990 to 2022 with first-line ILI/ILP, ICI, or TVEC for unresectable melanoma ITM. RESULTS: A total of 551 patients were treated, with ILI/ILP (n = 356), ICI (n = 125), and TVEC (n = 70) with median follow-up of 5.5 years. Tumor burden was highest with ILI/ILP and lowest with TVEC (p = .002). Breslow thickness was lowest with TVEC (p = .007). TVEC was mostly used in stage IIIB disease versus IIIC for ILI/ILP and ICI (p = .01). Using ICI as the reference category, TVEC had the highest odds of a complete response (CR) (odds ratio, 1.96; p = .029) and a longer local progression-free survival (PFS) (hazard ratio [HR], 0.40; p = .003). ILI/ILP had shorter local PFS (HR, 1.72; p = .012), PFS (HR, 1.79; p < .001), distant metastasis-free survival (DMFS) (HR, 1.75; p = .014), overall survival (HR, 1.82; p = .009), and melanoma-specific survival (HR, 2.29; p = .004). Stage IIIB disease had longer DMFS (HR, 0.24; p < .001) compared to IIIC/D. CONCLUSIONS: TVEC as first-line therapy for unresectable melanoma ITM was associated with superior CR rates and local PFS. Notably, TVEC was used in patients with a lower Breslow thickness, disease stage, and tumor burden. Therefore, when compared to ILI/ILP and ICI, TVEC should be considered as first-line therapy for unresectable stage IIIB melanoma ITM with minimal tumor burden and lower Breslow thickness.
背景：孤立肢体灌注和输注（ILI/ILP）一直是不可切除的黑色素瘤局部转移（ITM）的主要治疗方法，但免疫检查点抑制剂（ICI）和瘤内治疗（talimogene laherparepvec [TVEC]）的使用增加带来了几种不同的治疗选择。本研究比较一线ILI/ILP、ICI和TVEC。 方法：对12家国际机构进行回顾性分析，纳入1990年至2022年接受一线ILI/ILP、ICI或TVEC治疗不可切除黑色素瘤ITM的患者。 结果：共治疗551例患者，其中ILI/ILP（n = 356）、ICI（n = 125）和TVEC（n = 70），中位随访5.5年。ILI/ILP的肿瘤负荷最高，TVEC最低（p = 0.002）。TVEC的Breslow厚度最低（p = 0.007）。与ILI/ILP和ICI用于IIIC期疾病相比，TVEC大多用于IIIB期疾病（p = 0.01）。以ICI作为参照组，TVEC的完全缓解（CR）几率最高（优势比，1.96；p = 0.029），局部无进展生存期（PFS）更长（风险比[HR]，0.40；p = 0.003）。ILI/ILP的局部PFS较短（HR，1.72；p = 0.012）、PFS（HR，1.79；p < 0.001）、远处无转移生存期（DMFS）（HR，1.75；p = 0.014）、总生存期（HR，1.82；p = 0.009）和黑色素瘤特异性生存期（HR，2.29；p = 0.004）。与IIIC/D期相比，IIIB期疾病的DMFS更长（HR，0.24；p < 0.001）。 结论：TVEC作为不可切除黑色素瘤ITM的一线治疗与更高的CR率和局部PFS相关。值得注意的是，TVEC用于Breslow厚度、疾病分期和肿瘤负荷较低的患者。因此，与ILI/ILP和ICI相比，TVEC应被视为不可切除的IIIB期黑色素瘤ITM且肿瘤负荷最小和Breslow厚度较低的一线治疗方法。
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