Department of Radiation Oncology and Experimental Cancer Research, University Hospital Ghent, Ghent, Belgium; Immuno-Oncology Network Ghent, Ghent, Belgium.
Department of Radiation Oncology and Experimental Cancer Research, University Hospital Ghent, Ghent, Belgium; Immuno-Oncology Network Ghent, Ghent, Belgium.
Int J Radiat Oncol Biol Phys. 2018 Mar 15;100(4):906-915. doi: 10.1016/j.ijrobp.2017.11.029. Epub 2017 Nov 24.
To report the results of a phase 1 trial evaluating the safety of the ipilimumab/radiation therapy combination in patients with metastatic melanoma.
Thirteen patients with metastatic melanoma were enrolled. Trial treatment consisted of 4 cycles of ipilimumab in combination with concurrent dose-escalated high-dose radiation therapy to 1 lesion administered before the third cycle of ipilimumab.
Grade 3 or 4 ipilimumab-related adverse events occurred in 25% of patients. The maximum tolerated radiation therapy dose was not reached. Local control of the irradiated lesions was achieved in 11 of 12 irradiated patients (1 patient had progressive disease before irradiation and dropped out of the trial). Evaluation of the nonirradiated lesions demonstrated that 3 of 13 patients experienced clinical benefit, with 1 patient developing a partial response and 2 patients having confirmed stable disease. Immunomonitoring data showed that in patients without clinical benefit, factors linked to immunotolerance increased early after the initiation of ipilimumab, suggesting that early initiation of radiation therapy might be more effective if combined with ipilimumab.
Our findings suggest that the combination of ipilimumab and high-dose radiation therapy is feasible and safe.
报告一项评估 ipilimumab/放射治疗联合治疗转移性黑色素瘤患者安全性的 1 期试验结果。
共纳入 13 例转移性黑色素瘤患者。试验治疗包括 4 个周期的 ipilimumab 联合 3 个周期 ipilimumab 前给予的 1 个病灶的递增剂量高剂量放射治疗。
25%的患者出现 3 级或 4 级 ipilimumab 相关不良事件。未达到最大耐受放射治疗剂量。12 例接受放射治疗的患者中有 11 例（1 例在放射治疗前出现进展性疾病并退出试验）的照射病灶得到局部控制。对未照射病灶的评估显示，13 例患者中有 3 例（23%）有临床获益，其中 1 例患者出现部分缓解，2 例患者出现确认的稳定疾病。免疫监测数据表明，在无临床获益的患者中，与免疫耐受相关的因素在 ipilimumab 起始后早期增加，这表明如果与 ipilimumab 联合使用，早期开始放射治疗可能更有效。
我们的发现表明，ipilimumab 和高剂量放射治疗的联合是可行且安全的。
