Zhou Zixiang, Wang Hanping
Eight-year Medical Doctor Program, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Transl Lung Cancer Res. 2025 Jul 31;14(7):2875-2879. doi: 10.21037/tlcr-2025-341. Epub 2025 Jul 28.
Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but are frequently associated with immune-related adverse events (irAEs), which complicate treatment decisions. Patients who experience severe irAEs are often excluded from further immunotherapy due to concerns of recurrence. However, rechallenging ICIs in selected patients under close monitoring may offer long-term benefits, although evidence remains limited and heterogeneous.
We report a case of a 65-year-old man with stage IVB pulmonary adenocarcinoma harboring mutation and high tumor mutational burden. He initially received pembrolizumab-based chemoimmunotherapy but developed grade 4 hepatitis, requiring immunosuppressive treatment and discontinuation of ICIs. Subsequent tumor progression led to a rechallenge with ICIs alongside prophylactic tocilizumab. Although the patient experienced further grade 2 thyroiditis and grade 2 hypophysitis, all toxicities were manageable with hormone replacement and corticosteroids. A pacemaker was implanted for unrelated sick sinus syndrome. Despite intermittent symptoms, pembrolizumab monotherapy was maintained over a prolonged period, achieving durable tumor control with no progression noted at 4-year follow-up.
This case highlights that ICI rechallenge can be a viable and effective treatment strategy in selected patients with prior high-grade irAEs, especially when initial toxicities are well controlled and alternative causes of symptoms are carefully excluded. The prophylactic use of agents like tocilizumab may reduce the risk of irAE recurrence. This underscores the need for individualized risk-benefit assessment and close clinical monitoring in rechallenge scenarios.
免疫检查点抑制剂（ICIs）已改变癌症治疗方式，但常与免疫相关不良事件（irAEs）相关，这使治疗决策变得复杂。经历严重irAEs的患者常因担心复发而被排除在进一步的免疫治疗之外。然而，在密切监测下对选定患者重新使用ICIs可能会带来长期益处，尽管证据仍然有限且参差不齐。
我们报告一例65岁男性，患有IVB期肺腺癌，携带 突变且肿瘤突变负荷高。他最初接受基于派姆单抗的化疗免疫治疗，但出现了4级肝炎，需要进行免疫抑制治疗并停用ICIs。随后的肿瘤进展导致在预防性使用托珠单抗的同时重新使用ICIs。尽管患者出现了进一步的2级甲状腺炎和2级垂体炎，但所有毒性反应均可通过激素替代和皮质类固醇进行控制。因无关的病态窦房结综合征植入了起搏器。尽管有间歇性症状，但派姆单抗单药治疗仍长期维持，在4年随访中实现了持久的肿瘤控制，未发现进展。
该病例表明，对于先前有高级别irAEs的选定患者，重新使用ICIs可能是一种可行且有效的治疗策略，尤其是当初始毒性反应得到良好控制且仔细排除症状的其他原因时。预防性使用托珠单抗等药物可能会降低irAE复发的风险。这强调了在重新使用ICIs的情况下进行个体化风险效益评估和密切临床监测的必要性。
