Shanshal Mohamed, Maakaron Joseph, Parikh Kaushal, Moffett Jenesse Nicole, Luce Ailsa G, Schwecke Anna J, Molina Julian, Leventakos Konstantinos
Department of Oncology, Mayo Clinic, Rochester, MN, USA.
Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA.
Mediastinum. 2024 Nov 24;8:54. doi: 10.21037/med-24-20. eCollection 2024.
Thymoma is a rare mediastinal neoplasm originating from thymic epithelial cells, often associated with paraneoplastic syndromes. These syndromes can manifest as a range of autoimmune disorders, including myasthenia gravis, pure red cell aplasia, and aplastic anemia. Clinical trials involving the use of immune checkpoint inhibitors (ICIs) in thymoma have been complicated by a high incidence of immune-related adverse effects (irAEs). As a result, the use of ICIs in the treatment of thymoma is not currently recommended.
We present a case of thymoma with paraneoplastic aplastic anemia that showed a remarkable response to atezolizumab following the discontinuation of cyclosporine. The patient was initially treated with cisplatin, doxorubicin, and cyclophosphamide (CAP), achieving a short-term partial response. However, this response was not sustained, and she developed aplastic anemia characterized by worsening anemia, reticulocytopenia, and thrombocytopenia. A bone marrow biopsy revealed erythroid hypoplasia without dysplasia, linked to her thymoma. Cyclosporine was initiated to manage the aplastic anemia, but the disease continued to progress, leading to a switch to capecitabine and gemcitabine. Restaging scans revealed further advancement, with extensive pleural metastasis. To manage the progressing disease, atezolizumab was introduced. Initially, no response was seen while on cyclosporine, but after discontinuing cyclosporine, the patient experienced a significant therapeutic response. Despite this success, immune-related dermatitis and hematological complications developed, requiring careful management. In clinical trials, ICI use alongside immunosuppressants is common for managing paraneoplastic manifestations in thymoma.
This case highlights the potential efficacy of ICI in thymoma treatment, emphasizing the delicate balance required between immunosuppression and immunotherapy for optimal outcomes. Achieving this delicate balance is vital for optimizing patient outcomes while minimizing the risk of severe complications and ensuring that both the paraneoplastic syndrome and the tumor itself are adequately managed. This consideration is particularly important when developing future clinical trials for thymoma, where the complex interplay between these therapies must be carefully evaluated to design effective and safe treatment protocols.
胸腺瘤是一种罕见的起源于胸腺上皮细胞的纵隔肿瘤，常与副肿瘤综合征相关。这些综合征可表现为一系列自身免疫性疾病，包括重症肌无力、纯红细胞再生障碍和再生障碍性贫血。在胸腺瘤中使用免疫检查点抑制剂（ICI）的临床试验因免疫相关不良反应（irAE）的高发生率而变得复杂。因此，目前不建议在胸腺瘤治疗中使用ICI。
我们报告一例伴有副肿瘤性再生障碍性贫血的胸腺瘤病例，该病例在停用环孢素后对阿替利珠单抗表现出显著反应。患者最初接受顺铂、阿霉素和环磷酰胺（CAP）治疗，取得了短期部分缓解。然而，这种缓解未能持续，她出现了以贫血加重、网织红细胞减少和血小板减少为特征的再生障碍性贫血。骨髓活检显示红系发育不全但无发育异常，与她的胸腺瘤有关。开始使用环孢素治疗再生障碍性贫血，但疾病仍继续进展，导致改用卡培他滨和吉西他滨。重新分期扫描显示疾病进一步进展，伴有广泛的胸膜转移。为了控制疾病进展，引入了阿替利珠单抗。最初，在使用环孢素期间未观察到反应，但停用环孢素后，患者出现了显著的治疗反应。尽管取得了成功，但仍出现了免疫相关的皮炎和血液学并发症，需要仔细管理。在临床试验中，ICI与免疫抑制剂联合使用常用于治疗胸腺瘤的副肿瘤表现。
本病例突出了ICI在胸腺瘤治疗中的潜在疗效，强调了免疫抑制和免疫治疗之间为实现最佳结果所需的微妙平衡。实现这种微妙平衡对于优化患者预后、将严重并发症风险降至最低以及确保副肿瘤综合征和肿瘤本身都得到充分管理至关重要。在开展未来胸腺瘤临床试验时，这一考虑尤为重要，因为必须仔细评估这些疗法之间的复杂相互作用，以设计有效且安全的治疗方案。
