Gutzmer Ralf, Harrington Kevin J, Hoeller Christoph, Lebbé Celeste, Malvehy Josep, Öhrling Katarina, Downey Gerald, Dummer Reinhard
Haut-Tumour-Zentrum Hannover (HTZH), Klinik für Dermatologie, Allergologie und Venerologie, Medizinische Hochschule Hannover (MHH), Hannover, Germany.
NIHR Biomedical Research Centre, The Institute of Cancer Research, London, UK.
Eur J Dermatol. 2018 Dec 1;28(6):736-749. doi: 10.1684/ejd.2018.3447.
Talimogene laherparepvec, a herpes simplex virus type 1-based intralesional oncolytic immunotherapy, is approved in Europe for the treatment of adults with unresectable stage IIIB-IVM1a melanoma, with no bone, brain, lung or other visceral disease. It has direct oncolytic effects in injected lesions, leading to the release of tumour-derived antigens and systemic immune effects mediated by the induction of anti-tumour immunity, which is enhanced by the production of granulocyte macrophage colony-stimulating factor. Responses (which occur in >40% of stage IIIB-IVM1a patients) are often durable (>50% last ≥6 months) and occur in injected and uninjected lesions (in stage IIIB-IVM1c patients, 64%/34% of evaluable injected/uninjected non-visceral lesions, respectively, decreased in size by ≥50%). As with other immunotherapies, responses may be delayed or can arise after pseudoprogression. The pattern of treatment-emergent adverse events is distinct, being mostly grade 1/2, easy to manage, and rarely leading to treatment discontinuation. Systemic therapy represents the backbone of care for many metastatic melanoma patients. Nonetheless, the potential for durable locoregional control with a locally injected agent may make talimogene laherparepvec suitable for selected patients with stage IIIB/C disease, for whom surgery is not possible (e.g. with in-transit metastases, multiple melanoma lesions at different body sites, or those relapsing rapidly after repeated rounds of surgery) and slowly progressing disease. Here, we discuss which patients could be suitable for talimogene laherparepvec monotherapy based on the European indication, review the patterns/timing of response, and discuss the incidence/management of adverse events. Its potential use combined with immune checkpoint inhibitors is also discussed.
Talimogene laherparepvec是一种基于1型单纯疱疹病毒的瘤内溶瘤免疫疗法，在欧洲被批准用于治疗不可切除的IIIB-IVM1a期黑色素瘤成人患者，且无骨、脑、肺或其他内脏疾病。它对注射部位的病灶具有直接溶瘤作用，导致肿瘤衍生抗原的释放以及由抗肿瘤免疫诱导介导的全身免疫效应，粒细胞巨噬细胞集落刺激因子的产生可增强这种效应。反应（在IIIB-IVM1a期患者中发生率超过40%）通常持久（超过50%持续≥6个月），且在注射和未注射的病灶中均会出现（在IIIB-IVM1c期患者中，可评估的注射/未注射非内脏病灶分别有64%/34%大小缩小≥50%）。与其他免疫疗法一样，反应可能会延迟出现或在假性进展后出现。治疗中出现的不良事件模式不同，大多为1/2级，易于管理，很少导致治疗中断。全身治疗是许多转移性黑色素瘤患者治疗的主要手段。尽管如此，局部注射药物实现持久局部区域控制的潜力可能使Talimogene laherparepvec适用于某些无法进行手术的IIIB/C期疾病患者（例如有皮下转移、身体不同部位有多个黑色素瘤病灶，或在多次手术后迅速复发的患者）以及疾病进展缓慢的患者。在此，我们根据欧洲的适应症讨论哪些患者可能适合Talimogene laherparepvec单药治疗，回顾反应模式/时间，并讨论不良事件的发生率/管理。还讨论了其与免疫检查点抑制剂联合使用的潜在用途。
