PDF(Pubmed)
Abstract：
Mutations in the NRAS gene are common alterations in malignant melanoma. However, there are no specific treatment options approved for NRAS-mutated melanoma patients besides immune checkpoint inhibition. Since preclinical data suggests a synergistic effect of a MEK inhibitor (MEKi) and the oncolytic virus talimogene laherparepvec (T-VEC), we have treated three melanoma patients with this combination. All of the three patients had been suffering from recurring cutaneous and subcutaneous in-transit metastases. Upon treatment one patient (case 1) presented full regression of locoregional metastases and remained progression-free until date, for almost three years. The second patient (case 2) showed a partial regression of painful gluteal satellite metastases but died from brain metastases. The third patient (case 3) showed a durable response of locoregional metastases for seven months. The combination treatment was well tolerated with common adverse events known for each single agent. This report is the first case series presenting a clinical benefit of the combined T-VEC and MEKi treatment. We suggest the combination of T-VEC and MEKi as an off-label treatment option for patients with NRAS mutations, especially with recurrent in-transit or satellite metastases.
摘要：
NRAS基因突变是恶性黑色素瘤的常见改变。然而,除了免疫检查点抑制外,对于NRAS突变的黑色素瘤患者,没有批准的特定治疗方案.由于临床前数据表明MEK抑制剂（MEKi）和溶瘤病毒talimogenelaherparepvec（T-VEC）的协同作用，我们已经用这种组合治疗了三名黑色素瘤患者。所有三名患者都患有复发性皮肤和皮下运输转移。治疗后，一名患者（病例1）表现出局部转移完全消退，并且至今仍无进展，差不多三年了.第二例患者（病例2）显示出痛苦的臀部卫星转移的部分消退，但因脑转移而死亡。第三例患者（病例3）表现出持续7个月的局部转移反应。联合治疗对每种单一药物已知的常见不良事件具有良好的耐受性。本报告是第一个病例系列，介绍T-VEC和MEKi联合治疗的临床益处。我们建议T-VEC和MEKi的组合作为NRAS突变患者的非标记治疗选择。特别是在途中复发或卫星转移。
