Twenty to sixty percent of patients receiving immune checkpoint inhibitors (ICIs) experience high-grade immune-related adverse events (irAEs) which may prevent the continuation of treatment. Limited clinical evidence is available to guide treatment for these patients. Patients with stage IV or unresectable stage III melanoma at NYU Langone Health were reviewed from 1 January 2014 to 1 July 2019. Patients with first-line ICI systemic therapy, a high-grade irAE and a rechallenge with ICI therapy were included. Postrechallenge irAE recurrence, response rate, overall survival (OS) and progression-free survival (PFS) were evaluated. Postrechallenge irAEs recurred in 71.9% (n = 23/32) of patients at a median of 5.1 weeks from rechallenge, with 46.9% (15/32) recurring as high-grade events. Clinical response was achieved in 46.9% (15/32) of patients, including 40.6% (13/32) with a complete response and 6.3% (2/32) with partial response. Median OS from first ICI initiation was 85.4 weeks (45.7-140.7; 25th-75th percentile) and median PFS was 42.9 weeks (29.2-114.2; 25th-75th percentile). Patients with a shorter time to initial irAE and shorter time to postrechallenge irAE were at greater risk for disease progression [hazard ratio 7.80; 95% confidence interval (CI), 1.91-32.83; P = 0.004; hazard ratio 7.45, 95% CI, 1.57-35.35; P = 0.012). Those with greater duration to rechallenge (>10 weeks) were at lower risk for disease progression (hazard ratio 0.15, 0.03-0.68; P = 0.015). ICI rechallenge can be considered in patients with advanced melanoma, as the risk-benefit profile appears favorable. Treatment toxicity should be appropriately managed, as longer durations to rechallenge may lower the risk of disease progression.

中文翻译：

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晚期黑色素瘤患者发生高级免疫相关不良事件后对免疫检查点抑制剂再激发的反应。

接受免疫检查点抑制剂 (ICIs) 治疗的患者中有 20% 至 60% 会出现严重的免疫相关不良事件 (irAE)，这可能会阻碍治疗的继续。可用于指导这些患者治疗的临床证据有限。纽约大学 Langone Health 于 2014 年 1 月 1 日至 2019 年 7 月 1 日对患有 IV 期或不可切除的 III 期黑色素瘤的患者进行了审查。接受一线 ICI 全身治疗、高级别 irAE 和再次接受 ICI 治疗的患者均纳入其中。评估了再攻击后 irAE 复发、缓解率、总生存期 (OS) 和无进展生存期 (PFS)。重新给药后中位 5.1 周时，71.9% (n = 23/32) 的患者复发后 irAE，其中 46.9% (15/32) 复发为高级别事件。46.9% (15/32) 的患者获得临床缓解，其中完全缓解 40.6% (13/32)，部分缓解 6.3% (2/32)。首次 ICI 开始的中位 OS 为 85.4 周（45.7-140.7；第 25-75 个百分位），中位 PFS 为 42.9 周（29.2-114.2；第 25-75 个百分位）。初始 irAE 时间较短和再给药后 irAE 时间较短的患者疾病进展的风险更大[风险比 7.80；95%置信区间（CI），1.91-32.83；P=0.004；风险比 7.45，95% CI，1.57-35.35；P = 0.012）。重新挑战持续时间较长（>10周）的患者疾病进展风险较低（风险比0.15、0.03-0.68；P = 0.015）。对于晚期黑色素瘤患者，可以考虑重新进行 ICI 治疗，因为其风险效益似乎是有利的。应适当管理治疗毒性，因为较长的再攻击持续时间可能会降低疾病进展的风险。