Combined immunotherapy is associated with a significant risk of severe and potentially fatal immune-related adverse events (irAEs). Therefore, we retrospectively analyzed the side profile and efficacy of low-dose ipilimumab (1 mg/kg, IPI1) combined with anti-PD-1 immunotherapy in patients who progressed after anti-PD-1 monotherapy. Nine patients with unresectable stage III or IV melanoma treated with combined low-dose ipilimumab (1 mg/kg, IPI1) and anti-PD-1 immunotherapy, following progression after anti-PD-1 treatment, were identified. Treatment response and irAEs were recorded. Grade 3 irAEs occurred in one-third of patients. Interestingly, there were no grade 4 or 5 irAEs. In fact, four out of the nine patients experienced no irAEs at all. One patient discontinued combined immunotherapy due to immune-related colitis. The mean time to the onset of grade 3 irAEs was 14.3 weeks. The objective response rate was 33.3% and a disease control rate of 66.7% was achieved. Median progression-free survival (PFS) was 5.7 months and median overall survival (OS) was 21.6 months. The median PFS when IPI1 and anti-PD-1 treatment was administered in the second-line setting was not reached, but only 2.8 months when used in subsequent treatment settings. Combined IPI1 and anti-PD-1 immunotherapy was well tolerated. Its use in the third-line or above setting was associated with a significantly poorer prognosis than in the second-line setting. Larger, prospective studies are required to evaluate the safety and efficacy of this dosing regimen following anti-PD-1 treatment failure.

中文翻译：

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低剂量伊匹单抗联合抗PD-1免疫疗法治疗抗PD-1治疗失败后的转移性黑色素瘤患者。

联合免疫疗法与严重且可能致命的免疫相关不良事件 (irAE) 的显着风险相关。因此，我们回顾性分析了低剂量易普利姆玛（1 mg/kg，IPI1）联合抗PD-1免疫治疗对抗PD-1单药治疗后进展的患者的副作用和疗效。确定了 9 名不可切除的 III 期或 IV 期黑色素瘤患者，接受低剂量 ipilimumab（1 mg/kg，IPI1）和抗 PD-1 免疫疗法联合治疗，并在抗 PD-1 治疗后出现进展。记录治疗反应和 irAE。三分之一的患者出现 3 级 irAE。有趣的是，没有出现 4 级或 5 级 irAE。事实上，九名患者中有四人根本没有出现任何 irAE。一名患者因免疫相关结肠炎而停止联合免疫治疗。3 级 irAE 发生的平均时间为 14.3 周。客观缓解率为33.3%，疾病控制率为66.7%。中位无进展生存期 (PFS) 为 5.7 个月，中位总生存期 (OS) 为 21.6 个月。在二线治疗中进行 IPI1 和抗 PD-1 治疗时，中位 PFS 尚未达到，但在后续治疗中使用时，中位 PFS 仅为 2.8 个月。IPI1 和抗 PD-1 联合免疫疗法的耐受性良好。其在三线或以上环境中的使用与二线环境中的预后显着较差相关。需要进行更大规模的前瞻性研究来评估抗 PD-1 治疗失败后该给药方案的安全性和有效性。