Department of Hospital Medicine, Dartmouth-Hitchcock Medical Center.
Department of Hematology-Oncology, Norris Cotton Cancer Center, Lebanon, NH.
J Immunother. 2019 May;42(4):136-141. doi: 10.1097/CJI.0000000000000265.
Talimogene laherparepvec (T-VEC) is approved for unresected stage III-IV malignant melanoma. T-VEC has a direct cytotoxic effect and enhances the antitumor immunity of host cells. Immune checkpoints inhibitors also enhance the immunity of host cells by increasing the recruitment of antigen-presenting cells or activation and restoration of T-cell functions. Both type of therapies can potentiate the effect of the other therapy. We are reporting a case of T-VEC rechallenge who initially progressed on T-VEC with pembrolizumab but then responded to T-VEC rechallenge after intervening ipilimumab/nivolumab. An 83-year-old man developed a subungual lesion of the left thumb and found to have AJCC V. 7 stage IIIb melanoma. Few months later, he developed axillary lymphadenopathy and multiple subcutaneous nodules (AJCC V. 7 stage IIIc). The patient was started on intralesional rose Bengal and pembrolizumab. After 4 cycles of pembrolizumab with rose Bengal, a positron-emission tomography/computerized tomography scan showed the progression of disease. He was started on T-VEC intralesional injections with concurrent pembrolizumab, however, after 3 T-VEC injections and 2 more cycles of pembrolizumab, there was the progression of disease. Subsequently, ipilimumab/nivolumab was started and patient responded partially. Ipilimumab/nivolumab was held due to toxicity. Eight weeks from the last dose of ipilimumab/nivolumab, he experienced locoregional progression and was rechallenged with T-VEC monotherapy. The patient showed a significant response after second T-VEC injection and continued to show response 6 months since rechallenge. After, initial progression on T-VEC with pembrolizumab, intervening immune checkpoints inhibitors may favorably modify the antitumor immunity and potentiate antitumor effect of T-VEC rechallenge.
替莫唑胺（T-VEC）获批用于不可切除的 III-IV 期恶性黑色素瘤。T-VEC 具有直接细胞毒性作用，并增强宿主细胞的抗肿瘤免疫。免疫检查点抑制剂还通过增加抗原呈递细胞的募集或激活和恢复 T 细胞功能来增强宿主细胞的免疫。这两种类型的治疗都可以增强另一种治疗的效果。我们报告了一例 T-VEC 再挑战的病例，该患者最初在 T-VEC 加用 pembrolizumab 时进展，但在介入 ipilimumab/nivolumab 后对 T-VEC 再挑战有反应。一名 83 岁男性出现左手拇指的甲下病变，被诊断为 AJCC V.7 期 IIIb 黑色素瘤。几个月后，他出现腋窝淋巴结病和多个皮下结节（AJCC V.7 期 IIIc）。患者开始接受局部 rose Bengal 和 pembrolizumab 治疗。在 4 个周期的 pembrolizumab 联合 rose Bengal 治疗后，正电子发射断层扫描/计算机断层扫描显示疾病进展。他开始接受 T-VEC 局部注射，同时接受 pembrolizumab 治疗，但在 3 次 T-VEC 注射和 2 个周期的 pembrolizumab 后，疾病仍在进展。随后，开始使用 ipilimumab/nivolumab，患者部分缓解。由于毒性，停止使用 ipilimumab/nivolumab。在最后一次使用 ipilimumab/nivolumab 后 8 周，他出现局部区域进展，再次接受 T-VEC 单药治疗。第二次 T-VEC 注射后，患者出现明显缓解，自再次挑战以来，持续 6 个月仍有缓解。在 T-VEC 加用 pembrolizumab 初始进展后，介入免疫检查点抑制剂可能会有利地改变抗肿瘤免疫，并增强 T-VEC 再挑战的抗肿瘤效果。
