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纳武利尤单抗和伊匹单抗治疗转移性黑色素瘤患者的双重机制免疫相关贫血病例。

A case of dual-mechanism immune-related anaemia in a patient with metastatic melanoma treated with nivolumab and ipilimumab.

机构信息

Medicine, The University of Chicago Medicine Comprehensive Cancer Center, Chicago, Illinois, USA

Medicine, The University of Chicago Medicine Comprehensive Cancer Center, Chicago, Illinois, USA.

出版信息

J Immunother Cancer. 2020 Mar;8(1). doi: 10.1136/jitc-2019-000380.

Abstract

BACKGROUND

The combination of the immune checkpoint inhibitors (ICIs) ipilimumab and nivolumab is a mainstay of treatment for selected patients with metastatic melanoma. This combination also results in more frequent immune-related adverse events (irAEs) than either ICI alone. These irAEs can be severe and their pathogenesis is poorly understood.

CASE PRESENTATION

We report a case of a woman with metastatic melanoma, treated with combined ipilimumab and nivolumab, who developed severe anaemia. While initial workup revealed autoimmune haemolytic anaemia, the anaemia persisted despite corticosteroids and paradoxical reticulocytopenia was observed. Bone marrow biopsy demonstrated a CD8 T cell-mediated destruction of the red cell precursors implying concurrent pure red cell aplasia. Both processes resolved after the addition of cyclosporine A.

CONCLUSIONS

This report describes a rare case of two concurrent mechanisms of haematological irAE in a patient treated with combined ICI therapy. Successful treatment resulted only after the second underlying mechanism of toxicity was uncovered. Prompt recognition of these unusual presentations of rare irAEs is now key to effective irAE management.

摘要

背景

免疫检查点抑制剂(ICIs)伊匹单抗和纳武单抗联合使用是治疗某些转移性黑色素瘤患者的主要方法。与单独使用 ICI 相比,这种联合用药会导致更频繁的免疫相关不良事件(irAEs)。这些 irAEs 可能很严重,但其发病机制尚不清楚。

病例介绍

我们报告了一例转移性黑色素瘤女性患者,接受伊匹单抗和纳武单抗联合治疗后发生严重贫血。尽管最初的检查显示为自身免疫性溶血性贫血,但贫血持续存在,皮质类固醇治疗无效,并观察到矛盾性网织红细胞减少。骨髓活检显示 CD8 T 细胞介导的红细胞前体细胞破坏,提示同时发生纯红细胞再生障碍。加用环孢素 A 后,两种情况均得到缓解。

结论

本报告描述了一例接受联合 ICI 治疗的患者中两种同时发生的血液学 irAE 机制的罕见病例。只有在发现第二种潜在毒性机制后,治疗才取得成功。及时识别这些罕见 irAE 的不常见表现是有效 irAE 管理的关键。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a64b/7069276/48277495c17e/jitc-2019-000380f01.jpg

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