Talimogene laherparapvec (T-VEC) 是一种改良的 1 型单纯疱疹病毒 (HSV-1)，也是第一个被批准用于治疗不可切除黑色素瘤的溶瘤病毒。我们评估是否存在与肿瘤控制相关的肿瘤内在遗传因素。对接受 T-VEC 治疗的黑色素瘤患者进行了单机构回顾性分析。收集了大约 100 个基因的人口统计学、组织病理学报告、治疗史、临床结果和肿瘤基因组分析。确定了 93 名接受 T-VEC 的患者，其中 84 名 (91%) 被诊断为皮肤黑色素瘤。六十九 (69) 名患者接受了超过一剂 T-VEC，并且有足够的数据可用于临床分析。在这些患者中，30.0%（n = 21）有完全缓解的证据，定义为所有病变完全消退，无需额外的治疗或手术。 III 期疾病 (p < 0.001)、不存在宏观淋巴结疾病 (p < 0.001) 和不存在内脏/中枢神经系统转移 (p = 0.004) 均与单变量分析显示的任何临床反应或局部控制的证据相关。在分析时，54 名患者拥有可用的肿瘤遗传数据。至少一名患者体内有 60 个基因发生突变，除一名患者外，所有患者都至少鉴定出一种基因突变。通过多变量分析，TERT 启动子突变的存在与任何临床反应 (p = 0.043) 或局部控制 (p = 0.039) 的证据相关。这项工作描述了在单个机构中使用 T-VEC 治疗黑色素瘤的经验，并强调了TERT 启动子突变可能是临床反应的驱动因素。© 2024。作者。

Talimogene laherparapvec (T-VEC) is a modified herpes simplex virus type 1 (HSV-1) and the first oncolytic virus to be approved for the treatment of unresectable melanoma. We assessed whether there are tumor-intrinsic genetic factors that are associated with tumor control.A single-institution, retrospective analysis of melanoma patients treated with T-VEC was performed. Demographics, histopathologic reports, treatment history, clinical outcomes, and tumor genomic analysis of approximately 100 genes were collected.Ninety-three patients who had received T-VEC were identified, of whom 84 (91%) were diagnosed with cutaneous melanoma. Sixty-nine (69) patients received more than one dose of T-VEC and had sufficient data available for clinical analysis. Of these patients 30.0% (n = 21) had evidence of a complete response, defined as complete regression of all lesions without the need for additional treatment or procedures. Stage III disease (p < 0.001), absence of macroscopic nodal disease (p < 0.001), and absence of visceral/central nervous system metastases (p = 0.004) were all associated with evidence of any clinical response or local control by univariate analysis. At the time of analysis, 54 patients had tumor genetic data available. Sixty genes were mutated in at least one patient, and all but one patient had at least one gene mutation identified. Presence of TERT promotor mutation was associated with evidence of any clinical response (p = 0.043) or local control (p = 0.039) by multivariate analysis.This work describes the experience using T-VEC in melanoma at a single institution and highlights the presence of TERT promotor mutations as a possible driver of clinical response.© 2024. The Author(s).