Systemic versus local responses in melanoma patients treated with talimogene laherparepvec from a multi-institutional phase II study.
Systemic versus local responses in melanoma patients treated with talimogene laherparepvec from a multi-institutional phase II study.
复制标题
DOI：
10.1186/s40425-016-0116-2
复制
发表时间：
2016
影响因子：
10.9
通讯作者：
Senzer NN
中科院分区：
文献类型：
--
作者：
Kaufman HL;Amatruda T;Reid T;Gonzalez R;Glaspy J;Whitman E;Harrington K;Nemunaitis J;Zloza A;Wolf M;Senzer NN
我们之前报道过，talimogene laherparepvec 是一种编码粒细胞巨噬细胞集落刺激因子 (GM-CSF) 的溶瘤疱疹病毒，在一项 II 期临床试验中，晚期黑色素瘤患者的客观缓解率为 26%。然而，尚未报道个别病变的反应。由于 talimogene laherparepvec 被认为通过直接肿瘤细胞溶解和诱导全身肿瘤特异性免疫来介导抗肿瘤活性，因此我们试图确定病毒注射和非注射病变中的独立反应率。在一项多机构单臂开放标签 II 期临床试验中，50 名 IIIC 或 IV 期黑色素瘤患者接受了 talimogene laherparepvec 治疗。在这项研究中，患者接受治疗直至获得完全缓解、所有可触及的肿瘤消失、临床上显着的疾病进展或出现不可接受的毒性。本报告是对 talimogene laherparepvec 对注射病变和两种类型的非注射病变（非内脏病变和内脏病变）的全身影响的事后分析。 23 名患者中有 11 名 (47.8%) 未注射的非内脏病变总负担减少了 ≥30%，12 名患者中有 2 名 (16.7%) 内脏病变总负担减少了 ≥30%。在直接注射 talimogene laherparepvec 的 128 个可评估病灶中，86 个 (67.2%) 的病灶大小减小了 ≥ 30%，59 个 (46.1%) 完全消退。在 146 个未注射的非内脏病变中，60 个 (41.1%) 的大小减小了 ≥30%，其中大多数 (44 个 [30.1%]) 完全消退。在 32 个内脏病变中，4 个 (12.5%) 的大小减小了 ≥ 30%，3 个 (9.4%) 完全消退。直接注射的病变的病变反应中位时间最短（18.4周），其次是未注射的非内脏病变（23.1周）和内脏病变（51.3周），这与talimogene laherparepvec延迟的区域和全身抗肿瘤免疫反应的启动一致。这些结果支持talimogene laherparepvec 免疫疗法对晚期黑色素瘤患者的区域和全身作用。
We previously reported that talimogene laherparepvec, an oncolytic herpes virus encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), resulted in an objective response rate of 26 % in patients with advanced melanoma in a phase II clinical trial. The response of individual lesions, however, was not reported. Since talimogene laherparepvec is thought to mediate anti-tumor activity through both direct tumor cytolysis and induction of systemic tumor-specific immunity, we sought to determine the independent response rate in virus-injected and non-injected lesions. Fifty patients with stage IIIC or IV melanoma were treated with talimogene laherparepvec in a multi-institutional single-arm open-label phase II clinical trial. In this study patients were treated until a complete response was achieved, all accessible tumors disappeared, clinically significant disease progression, or unacceptable toxicity. This report is a post hoc analysis of the systemic effects of talimogene laherparepvec in injected lesions and two types of uninjected lesions—non-visceral lesions and visceral lesions. Eleven of 23 patients (47.8 %) had a ≥ 30 % reduction in the total burden of uninjected non-visceral lesions, and 2 of 12 patients (16.7 %) had a ≥ 30 % reduction in the total burden of visceral lesions. Among 128 evaluable lesions directly injected with talimogene laherparepvec, 86 (67.2 %) decreased in size by ≥ 30 % and 59 (46.1 %) completely resolved. Of 146 uninjected non-visceral lesions, 60 (41.1 %) decreased in size by ≥ 30 %, the majority of which (44 [30.1 %]) completely resolved. Of 32 visceral lesions, 4 (12.5 %) decreased in size by ≥ 30 %, and 3 (9.4 %) completely resolved. The median time to lesion response was shortest for lesions that were directly injected (18.4 weeks), followed by uninjected non-visceral lesions (23.1 weeks) and visceral lesions (51.3 weeks), consistent with initiation of a delayed regional and systemic anti-tumor immune response to talimogene laherparepvec. These results support a regional and systemic effect of talimogene laherparepvec immunotherapy in patients with advanced melanoma.