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发生帕博利珠单抗诱导的吉兰-巴雷综合征毒性的不可切除转移性黑色素瘤患者的治疗考量:一例报告

Treatment Considerations for Patients with Unresectable Metastatic Melanoma Who Develop Pembrolizumab-Induced Guillain-Barré Toxicity: A Case Report.

作者信息

Muralikrishnan Sivraj, Ronan Lara K, Coker Shodeinde, Rauschkolb Paula K, Shirai Keisuke

机构信息

Department of Hematology/Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.

Department of Neurology and Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.

出版信息

Case Rep Oncol. 2020 Jan 21;13(1):43-48. doi: 10.1159/000504930. eCollection 2020 Jan-Apr.

Abstract

Immunotherapy has improved outcomes in many malignancies, most notably in melanoma, lung cancer, and bladder cancer. Understanding the side effects associated with these medications is an important part of managing our patients. Although fatigue, rash, and diarrhea are commonly reported side effects, it is important to be cognizant of rarer ones, such as neuropathy. Amongst the different neurological toxicities that have been reported in the literature, Guillain-Barré-like neuropathies are quite rare. However, the occurrence of such neuropathies in a patient can be life threatening. The problem this poses in treating cancers such as melanoma is that it eliminates an effective class of medication available to the patient, which can ultimately affect their prognosis. We present a case of a 65-year-old female with unresectable metastatic melanoma who developed Guillain-Barré-like neuropathy after two doses of pembrolizumab. Her clinical course was complicated by three separate hospitalizations over 3 months due to recurring bouts of neuropathy, which resulted in a significant decline in performance status and delay in subsequent treatment of her melanoma. Her prolonged recovery eventually resulted in progression of her melanoma nearly 1 year later, while off therapy. Instead of discontinuing immunotherapy completely, she agreed to a re-challenge with ipilimumab. After one dose, her melanoma regressed and continues to show a sustained response nearly 1 year after treatment without any signs of relapse in her neuropathy. Guillain-Barré toxicity resulting from immune checkpoint inhibition poses a difficult challenge to an oncologist who is determining the next line of treatment for patients with unresectable metastatic melanoma that have progressed while off therapy and who have no targetable mutations. Our case raises the question of whether a re-challenge with a different class of immunotherapy agent is a reasonable option.

摘要

免疫疗法已改善了许多恶性肿瘤的治疗结果,最显著的是在黑色素瘤、肺癌和膀胱癌方面。了解这些药物相关的副作用是管理我们患者的重要组成部分。虽然疲劳、皮疹和腹泻是常见报告的副作用,但认识到较罕见的副作用(如神经病变)也很重要。在文献中报道的不同神经毒性中,吉兰-巴雷样神经病变相当罕见。然而,患者出现此类神经病变可能危及生命。这在治疗黑色素瘤等癌症时带来的问题是,它使患者无法使用一类有效的药物,最终可能影响其预后。我们报告一例65岁女性,患有不可切除的转移性黑色素瘤,在接受两剂派姆单抗后出现吉兰-巴雷样神经病变。她的临床病程因神经病变反复发作在3个月内三次住院而复杂化,这导致其体能状态显著下降,并延误了黑色素瘤的后续治疗。她的长期康复最终导致其黑色素瘤在停止治疗近1年后进展。她没有完全停止免疫治疗,而是同意再次使用伊匹单抗。一剂后,她的黑色素瘤消退,在治疗近1年后仍持续有反应,且神经病变无任何复发迹象。免疫检查点抑制导致的吉兰-巴雷毒性给肿瘤学家带来了一个难题,即对于在停止治疗时病情进展且无可靶向突变的不可切除转移性黑色素瘤患者,确定下一步治疗方案。我们的病例提出了一个问题,即再次使用不同类别的免疫治疗药物是否是一个合理的选择。

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Acute demyelinating polyneuropathy induced by nivolumab.纳武单抗诱发的急性脱髓鞘性多发性神经病。
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