Dollin Yonatan, Rubin Jason, Carvajal Richard D, Rached Helene, Nitzkorski James R
Department of Medicine, Wright State University, USA.
Department of Medical Oncology, Vassar Brothers Medical Center, Poughkeepsie, NY, USA.
Int J Surg Case Rep. 2020;77:591-594. doi: 10.1016/j.ijscr.2020.11.063. Epub 2020 Nov 16.
Tavokinogene Telseplasmid Electroporation Therapy (TAVO) and Pembrolizumab therapy is being studied in subjects with immune checkpoint inhibitor (ICI) resistant melanoma. TAVO is a novel office-based local therapy shown to be effective in patients with advanced melanoma. The technique involves the direct injection of a plasmid encoding IL-12 into an accessible tumor driven by electroporation. The tumor cells have then been shown to express high levels of IL-12 resulting in a local inflammatory response within the tumor microenvironment.
The patient with stage IIB, pT3b melanoma was treated with primary tumor resection and found to have a negative sentinel node biopsy. She subsequently developed regional recurrence and was treated with inguinal lymphadenectomy and adjuvant Nivolumab. Despite therapy, she had progression of disease with skin and subcutaneous metastases (in-transit lesions), brain and liver lesions, hilar and iliac nodal disease. She was transitioned to nivolumab + ipilimumab, and Talimogene Laherparepvec (T-VEC) therapy for the in-transit lesions, without success. Stereotactic radiosurgery was used for the brain metastasis. Groin subcutaneous and in-transit lesions were treated with TAVO and intravenous pembrolizumab. Serial physical exams and CT scans were used to assess response.
All lesions treated with TAVO resolved. An abscopal response was also noted: hilar and mediastinal lymphadenopathy resolved. The liver mass and pelvic lymphadenopathy decreased in size, and her brain metastasis remained stable after radiation.
This case suggests that combination TAVO and Pembrolizumab is a safe and effective local treatment for ICI resistant metastatic melanoma in the setting of rheumatoid arthritis. An abscopal effect was also noted through control of systemic disease.
正在对免疫检查点抑制剂（ICI）耐药的黑色素瘤患者进行替沃基因特尔质粒电穿孔疗法（TAVO）联合帕博利珠单抗治疗的研究。TAVO是一种新型的门诊局部治疗方法，已证明对晚期黑色素瘤患者有效。该技术包括通过电穿孔将编码白细胞介素-12（IL-12）的质粒直接注射到可触及的肿瘤中。然后已证明肿瘤细胞会表达高水平的IL-12，从而在肿瘤微环境中引发局部炎症反应。
一名患有IIB期、pT3b黑色素瘤的患者接受了原发性肿瘤切除术，前哨淋巴结活检结果为阴性。她随后出现区域复发，接受了腹股沟淋巴结清扫术和辅助性纳武单抗治疗。尽管进行了治疗，但她的疾病仍进展，出现皮肤和皮下转移（移行性病变）、脑和肝病变、肺门和髂淋巴结疾病。她转而接受纳武单抗+伊匹单抗治疗，并使用塔利莫基因拉罗帕韦克（T-VEC）治疗移行性病变，但均未成功。立体定向放射外科用于治疗脑转移瘤。腹股沟皮下和移行性病变采用TAVO和静脉注射帕博利珠单抗治疗。通过系列体格检查和CT扫描评估反应。
所有接受TAVO治疗的病变均消退。还观察到远隔效应：肺门和纵隔淋巴结病消退。肝脏肿块和盆腔淋巴结病大小减小，放疗后她的脑转移瘤保持稳定。
该病例表明，在类风湿性关节炎背景下，TAVO联合帕博利珠单抗是治疗ICI耐药转移性黑色素瘤的一种安全有效的局部治疗方法。通过控制全身疾病还观察到了远隔效应。
