Melanoma Institute Australia, The University of Sydney, Sydney, Australia.
Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, Australia.
Eur J Cancer. 2023 Jun;186:12-21. doi: 10.1016/j.ejca.2023.03.006. Epub 2023 Mar 11.
Differing doses of ipilimumab (IPI) are used in combination with an anti-PD1 antibody in advanced melanoma. There is no data on the outcomes of patients who progress following low-dose IPI (< 3 mg/kg) and are subsequently treated with IPI 3 mg/kg (IPI3). We conducted a multicentre retrospective survey to assess the efficacy of this strategy.
Patients with resected stage III, unresectable stage III or IV melanoma who received low dose IPI (< 3 mg/kg) with an anti-PD1 antibody with recurrence (neo/adjuvant) or progressive disease (metastatic), who then received IPI3± anti-PD1 antibody were eligible. Best investigator-determined Response Evaluation Criteria in Solid Tumours response, progression-free survival (PFS) and overall survival (OS) were analysed.
Total 36 patients received low-dose IPI with an anti-PD1 antibody, 18 (50%) in the neo/adjuvant and 18 (50%) in the metastatic setting. Of which, 20 (56%) had primary resistance and 16 (44%) had acquired resistance. All patients received IPI3 for unresectable stage III or IV melanoma; median age 60 (29-78), 18 (50%) M1d disease, 32 (89%) Eastern Cooperative Oncology Group performance status 0-1. Around 35 (97%) received IPI3 with nivolumab and 1 received IPI3 alone. The response rate to IPI3 was 9/36 (25%). In patients with primary resistance, the response rate was 6/20 (30%). After a median follow-up of 22 months (95% CI: 15-27 months), the median PFS and OS were not reached in patients who responded; 1-year PFS and OS were 73% and 100%, respectively.
IPI3 following recurrence/progression on low dose IPI has clinical activity, including in primary resistance. IPI dosing is therefore critical in a subset of patients.
在晚期黑色素瘤中，不同剂量的伊匹单抗（IPI）与抗 PD-1 抗体联合使用。对于低剂量 IPI（<3mg/kg）治疗后进展的患者，随后用 IPI 3mg/kg（IPI3）治疗的患者的结局数据尚不清楚。我们进行了一项多中心回顾性调查，以评估该策略的疗效。
接受低剂量 IPI（<3mg/kg）与抗 PD-1 抗体联合治疗的可切除 III 期、不可切除 III 期或 IV 期黑色素瘤患者，出现复发（新辅助/辅助）或疾病进展（转移性），随后接受 IPI3±抗 PD-1 抗体治疗，符合条件。最佳研究者确定的实体瘤反应评估标准（Response Evaluation Criteria in Solid Tumours，RECIST）反应、无进展生存期（progression-free survival，PFS）和总生存期（overall survival，OS）进行了分析。
共有 36 例患者接受了低剂量 IPI 与抗 PD-1 抗体联合治疗，其中 18 例（50%）为新辅助/辅助治疗，18 例（50%）为转移性治疗。其中，20 例（56%）患者存在原发性耐药，16 例（44%）患者存在获得性耐药。所有患者均因不可切除的 III 期或 IV 期黑色素瘤接受了 IPI3 治疗；中位年龄 60（29-78）岁，18 例（50%）为 M1d 疾病，32 例（89%）为东部肿瘤协作组体力状态 0-1 分。约 35 例（97%）患者接受了 IPI3 联合 nivolumab 治疗，1 例患者接受了 IPI3 单药治疗。IPI3 的缓解率为 9/36（25%）。在原发性耐药患者中，缓解率为 6/20（30%）。中位随访 22 个月（95%CI：15-27 个月）后，缓解患者的中位 PFS 和 OS 均未达到；1 年 PFS 和 OS 分别为 73%和 100%。
在低剂量 IPI 治疗后复发/进展的情况下，使用 IPI3 具有临床活性，包括原发性耐药患者。因此，在某些患者中，IPI 的剂量非常关键。
