Supplementary Material for: Use of Talimogene Laherparepvec to Treat Cutaneous Squamous Cell Carcinoma in a Renal Transplant Patient

A 66-year-old female with a history of two renal transplants due to recurrent thrombotic thrombocytopenic purpura presented to clinic with multiple lesions identified to be non-metastatic cutaneous squamous cell carcinoma (CSCC). The patient previously underwent multiple Mohs procedures and radiation therapy treatment but continued to develop CSCC lesions with increasing frequency. After discussing multiple treatment options, it was elected to pursue treatment with Talimogene laherparepvec (T-VEC) given the systemic immune responses it can cause, with low theoretical risk of graft rejection. After starting intratumoral T-VEC injections, treated lesions began to decrease in size, and a reduction in the rate of new CSCC lesions was observed. Treatment was held due to unrelated renal complications during which time new CSCCs developed. Patient was restarted on T-VEC therapy with no recurrent renal issues. Upon reinitiating treatment, injected and non-injected lesions showed reduction in size, and the development of new lesions again ceased. One injected lesion was resected via Mohs micrographic surgery due to its size and discomfort. On sectioning, this demonstrated an exuberant lymphocytic perivascular infiltrate which was consistent with treatment response to T-VEC, with little active tumor. With high rates of non-melanoma skin cancer in renal transplant patients, their transplant status significantly limits treatment options, specifically with regards to anti-PD-1 therapy. This case suggests T-VEC can generate local and systemic immune responses in the setting of immunosuppression and that T-VEC may be a beneficial therapeutic option for transplant patients with CSCC.一名66岁女性，因复发性血栓性血小板减少性紫癜（thrombotic thrombocytopenic purpura）接受过两次肾移植，因多发皮损就诊，经确诊为非转移性皮肤鳞状细胞癌（cutaneous squamous cell carcinoma, CSCC）。患者此前曾接受多次莫氏手术（Mohs procedure）与放射治疗，但仍持续出现CSCC皮损，且新发频率逐渐升高。经多方讨论治疗方案后，临床选择予以塔利莫热帕雷普维克（Talimogene laherparepvec, T-VEC）治疗，因其可诱发全身性免疫反应，理论上移植物排斥风险较低。启动瘤内T-VEC注射治疗后，受累皮损体积开始缩小，新发CSCC皮损的速率亦有所降低。后因无关肾脏并发症暂停治疗，此期间再次出现新发CSCC皮损。患者随后重启T-VEC治疗，未再出现肾脏相关不良事件。重新启动治疗后，注射与未注射的皮损均出现体积缩小，新发皮损再次停止出现。其中一处注射部位的皮损因体积较大且引发不适，通过莫氏显微手术切除。病理切片显示，该皮损存在显著的淋巴细胞血管周围浸润，符合T-VEC的治疗反应特征，仅残留少量活跃肿瘤。肾移植患者中非黑色素瘤皮肤癌的发病率较高，而移植状态极大限制了治疗选择，尤以抗PD-1治疗（anti-PD-1 therapy）为甚。本病例表明，在免疫抑制状态下，T-VEC可引发局部与全身性免疫反应，或可成为肾移植合并CSCC患者的有效治疗选择。