Nagpal Chitrakshi, Rastogi Sameer, Shamim Shamim A, Prakash Sneha
Department of Medicine, All India Institute of Medical Sciences, New Delhi 110029, India.
Department of Medical Oncology, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi 110029, India.
Ecancermedicalscience. 2023 Dec 8;17:1644. doi: 10.3332/ecancer.2023.1644. eCollection 2023.
Immune checkpoint inhibitors (ICIs) are associated with specific immune-related adverse events (irAEs) which are unique compared to cytotoxic chemotherapy. For life-threatening adverse events including grade 3 or more, permanent discontinuation of the ICIs is recommended, albeit without much robust evidence. Safe re-challenge of ICIs with concurrent immunosuppression has been reported with irAEs like gastrointestinal toxicity and arthritis. Here we present a case of a lady with undifferentiated pleomorphic sarcoma with programmed death ligand1 expression, who showed a complete response to pembrolizumab used as third-line therapy. However, it had to be stopped after 22 doses when the patient developed grade 3 pneumonitis. In view of progression off pembrolizumab, and lack of other effective alternatives, pembrolizumab was re-challenged with concurrent interleukin-6 (IL-6) blockade using tocilizumab. This was based on preliminary evidence on the role of IL-6 in mediating the irAEs, especially pneumonitis. The patient re-attained a complete response with pembrolizumab. There was no recurrence of the pneumonitis after rechallenging, and there was partial radiographic resolution of the ICI-interstitial lung disease after the combination therapy.
免疫检查点抑制剂（ICIs）与特定的免疫相关不良事件（irAEs）相关，这些不良事件与细胞毒性化疗相比具有独特性。对于包括3级及以上的危及生命的不良事件，尽管没有太多确凿证据，但仍建议永久停用ICIs。有报道称，对于胃肠道毒性和关节炎等irAEs，在同时进行免疫抑制的情况下安全重新使用ICIs。在此，我们报告一例未分化多形性肉瘤且程序性死亡配体1表达阳性的女性病例，该患者对作为三线治疗使用的帕博利珠单抗表现出完全缓解。然而，在患者出现3级肺炎后，在使用22剂后不得不停药。鉴于停用帕博利珠单抗后疾病进展，且缺乏其他有效替代方案，遂使用托珠单抗同时阻断白细胞介素-6（IL-6），对帕博利珠单抗进行重新使用。这是基于IL-6在介导irAEs尤其是肺炎中作用的初步证据。该患者再次使用帕博利珠单抗后再次获得完全缓解。重新使用后肺炎未复发，联合治疗后ICI相关性间质性肺病的影像学表现部分缓解。
