免疫检查点抑制剂治疗后的免疫相关性中性粒细胞减少症。
Immune-related Neutropenia Following Treatment With Immune Checkpoint Inhibitors.
机构信息
Thoracic Cancer Service, Davidoff Cancer Center.
Thoracic Cancer Service, Rambam Health Care Campus, Haifa.
出版信息
J Immunother. 2020 Feb/Mar;43(2):67-74. doi: 10.1097/CJI.0000000000000293.
The existing data with regard to immune-related neutropenia (irN), a rare (incidence-1%) immune-related adverse event of immune checkpoint inhibitors, are scarce. Eight patients with irN were identified through internal databases of 3 participating Israeli cancer centers. In addition, 11 original articles focusing on the clinical course of 24 patients with irN were selected during the PubMed search. Descriptive analysis of clinical and pathologic factors related to irN was performed (n=32); the effect of these on the irN outcomes was assessed. An algorithm for irN evaluation and treatment was proposed. The median time-to-onset of irN (n=32) was 60 days (range, 10-465 d). Grade 3-5 irN, febrile neutropenia, and irN-related death occurred in 81%, 50%, and 9% of patients, respectively. In all, 56%, 22%, 62%, and 25% of patients received PO corticosteroids, IV corticosteroids, granulocyte colony-stimulating factor (GCSF), and intravenous immunoglobulins (IVIG), respectively, with an improvement/resolution rate of 84%. Odds ratios for irN improvement/resolution were as follows: 1.40 [95% confidence interval (CI), 0.03-68.72], 0.43 (95% CI, 0.04-4.22), 2.60 (95% CI, 0.07-97.24), 0.36 (95% CI, 0.03-4.38), 4.02 (95% CI, 0.16-99.48), 2.01 (95% CI, 0.32-12.70), 1.08 (95% CI, 0.02-49.89), 0.42 (95% CI, 0.06-2.91), and 2.73 (95% CI, 0.42-17.51) for granulocyte hyperplasia, granulocyte/all lineage hypoplasia, granulocyte maturation blockade, lymphocyte infiltration on bone marrow biopsy, IV corticosteroids, PO corticosteroids, cyclosporine, IVIG, and GCSF, respectively (P>0.05 for all factors). IrN recurrence rate following immune checkpoint inhibitors rechallenge was 80%. IrN is a rare, life-threatening, early-onset immune-related adverse event. Differentiating between the central, peripheral, and modified peripheral types allows a better prognosis definition. Corticosteroids and GCSF represent the main treatment approaches; IVIG and cyclosporine should be used as salvage treatment.
目前关于免疫相关性中性粒细胞减少症（irN）的现有数据很少，irN 是免疫检查点抑制剂罕见的（发生率为 1%）免疫相关不良事件。通过 3 家参与的以色列癌症中心的内部数据库，确定了 8 例 irN 患者。此外，在 PubMed 搜索中选择了 11 篇重点研究 24 例 irN 患者临床过程的原始文章。对与 irN 相关的临床和病理因素进行了描述性分析（n=32）；评估了这些因素对 irN 结果的影响。提出了 irN 评估和治疗的算法。irN（n=32）的中位发病时间为 60 天（范围，10-465 天）。3-5 级 irN、发热性中性粒细胞减少症和 irN 相关死亡分别发生在 81%、50%和 9%的患者中。接受口服皮质类固醇、静脉皮质类固醇、粒细胞集落刺激因子（GCSF）和静脉注射免疫球蛋白（IVIG）治疗的患者分别为 56%、22%、62%和 25%，缓解率为 84%。irN 缓解的优势比如下：粒细胞增生 1.40（95%置信区间（CI），0.03-68.72），粒细胞/所有谱系减少 0.43（95%CI，0.04-4.22），粒细胞成熟阻滞 2.60（95%CI，0.07-97.24），淋巴细胞浸润骨髓活检 0.36（95%CI，0.03-4.38），静脉皮质类固醇 4.02（95%CI，0.16-99.48），口服皮质类固醇 2.01（95%CI，0.32-12.70），环孢素 1.08（95%CI，0.02-49.89），静脉免疫球蛋白 0.42（95%CI，0.06-2.91），粒细胞集落刺激因子 2.73（95%CI，0.42-17.51）（所有因素的 P>0.05）。免疫检查点抑制剂再挑战后的 irN 复发率为 80%。irN 是一种罕见的、危及生命的、早期发生的免疫相关不良事件。区分中枢型、外周型和改良外周型有助于更好地定义预后。皮质类固醇和 GCSF 是主要的治疗方法；静脉注射免疫球蛋白和环孢素应作为挽救治疗。
Zotero 插件