Hernandez-Martinez Juan-Manuel, Rios-Garcia Eduardo, Palomares-Palomares Cittim B, Arrieta Oscar
Thoracic Oncology Unit and Experimental Oncology Laboratory, Instituto Nacional de Cancerologiía de Meíxico (INCan), Mexico City, Mexico.
Secretaría de Ciencia, Humanidades, Tecnología e Innovación (SECIHTI)-Instituto Nacional de Cancerología, Mexico City, Mexico.
Front Immunol. 2025 Jul 3;16:1586426. doi: 10.3389/fimmu.2025.1586426. eCollection 2025.
Immune-hemolytic anemia (IHA) is a rare immune-related adverse event (irAE) in cancer patients treated with immune-checkpoint inhibitors (ICIs). Although several cases of ICI-associated IHA have been reported, few attempts have been made to collate available information. This scoping review aims to provide a comprehensive description of the clinical features of ICI-associated IHA.
PubMed and Web of Science Core Collection databases were searched for articles published in English from January 2006 to January 2025 on ICI-associated IHA. Only full-text publications reporting the clinical characteristics of patients with ICI-associated IHA were included. Two authors independently assessed the search results for eligibility and extracted the following information: author, publication year, patient characteristics, and IHA features.
Among 54 publications, published between July 2014 and March 2024, 92 cases of ICI-associated IHA were identified, revealing a high proportion of cases in patients with melanoma (45.2%) and non-small-cell lung cancer (31%). Approximately half of the cases occurred in patients receiving ICIs as first-line systemic therapy, with IHA manifesting after a median of 3 cycles. The most frequent triggering ICIs were pembrolizumab (41.3%) and nivolumab (26.1%). A high proportion of cases involved patients with a medical history of hematolymphoid tumors (34.8%), hypertension (15.2%), and anemia/AIHA (15.2%). Initial management involved ICI discontinuation (94.6%), high-dose glucocorticoids therapy (97.8%), and transfusion support (63%), with treatment responses achieved in most cases (91.3%). Only 2 cases reported fatal outcomes. IHA relapse was documented in only 7 of 23 (30.4%) patients who were rechallenged with an ICI.
To the best of our knowledge, this is the largest scoping review of population-based studies, case reports, and case series on ICI-associated IHA. The evidence reviewed suggests that patients with specific comorbidities may be at higher risk of developing ICI-associated IHA. In the absence of predictive tools to individually estimate the risk of this complication, a list of frequently reported co-occurring conditions in cases of ICI-associated IHA may help select patients who could benefit from closer surveillance.
免疫性溶血性贫血（IHA）是接受免疫检查点抑制剂（ICI）治疗的癌症患者中一种罕见的免疫相关不良事件（irAE）。尽管已有几例ICI相关IHA的病例报告，但很少有人尝试整理现有信息。本范围综述旨在全面描述ICI相关IHA的临床特征。
在PubMed和Web of Science核心合集数据库中检索2006年1月至2025年1月期间以英文发表的关于ICI相关IHA的文章。仅纳入报告ICI相关IHA患者临床特征的全文出版物。两位作者独立评估检索结果的 eligibility，并提取以下信息：作者、发表年份、患者特征和IHA特征。
在2014年7月至2024年3月期间发表的54篇出版物中，确定了92例ICI相关IHA病例，显示黑色素瘤患者（45.2%）和非小细胞肺癌患者（31%）中病例比例较高。约一半的病例发生在接受ICI作为一线全身治疗的患者中，IHA在中位3个周期后出现。最常引发的ICI是帕博利珠单抗（41.3%）和纳武利尤单抗（26.1%）。很大比例的病例涉及有血液淋巴系统肿瘤病史（34.8%）、高血压（15.2%）和贫血/自身免疫性溶血性贫血（15.2%）的患者。初始治疗包括停用ICI（94.6%）、高剂量糖皮质激素治疗（97.8%）和输血支持（63%），大多数病例（91.3%）取得了治疗反应。仅2例报告了致命结局。在23例接受ICI再激发的患者中，只有7例（30.4%）记录了IHA复发。
据我们所知，这是对基于人群的研究、病例报告和病例系列关于ICI相关IHA的最大范围综述。所审查的证据表明，患有特定合并症的患者可能发生ICI相关IHA的风险更高。在缺乏单独估计这种并发症风险的预测工具的情况下，ICI相关IHA病例中经常报告的共病情况列表可能有助于选择可能从密切监测中受益的患者。
