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类固醇难治性检查点抑制剂性肺炎的危险因素和免疫调节剂的应用。

Risk factors and immunomodulators use in steroid-refractory checkpoint inhibitor pneumonitis.

机构信息

Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China

Department of Radiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

出版信息

J Immunother Cancer. 2023 Jun;11(6). doi: 10.1136/jitc-2023-006982.

Abstract

BACKGROUND

Checkpoint inhibitor pneumonitis (CIP) that does not respond to corticosteroids is termed steroid-refractory CIP. We aimed to find risk factors of steroid-refractory CIP and evaluate the management strategies of immunomodulators (IMs).

METHODS

Patients with CIP were identified between August 2019 and August 2022 retrospectively. Clinical characteristics, peripheral blood biomarkers, and radiologic images were collected.

RESULTS

Among 1209 patients with solid tumor receiving programmed death (ligand)-1 antibody, 28 patients developed steroid-refractory CIP and 38 patients developed steroid-response CIP. Patients with steroid-refractory CIP had a higher proportion of previous interstitial lung disease (p=0.015) and grade 3-4 (p<0.001) at diagnosis. Otherwise, absolute neutrophil count (ANC), procalcitonin were higher and albumin was lower in steroid-refractory patients (ANC, p=0.009; procalcitonin, p=0.024; albumin, p=0.026). After multivariate analysis, grade 3-4 and higher ANC at diagnosis were confirmed to be independent risk factors for steroid-refractory CIP (grade, p=0.001; ANC, p=0.046). For grade 2 steroid-refractory CIP, additional IMs did not affect the prognosis (p=1.000). However, additional IMs reduced the risk of deterioration significantly in grade 3-4 steroid-refractory CIP (p=0.036).

CONCLUSIONS

Grade 3-4 and higher peripheral blood ANC at diagnosis are associated with higher risk of steroid-refractory CIP. The use of additional IMs improves the outcome of grade 3-4 steroid-refractory CIP. These results can offer new insights to the decision-making of CIP management.

摘要

背景

对皮质类固醇无反应的检查点抑制剂性肺炎(CIP)被称为皮质类固醇难治性 CIP。我们旨在寻找皮质类固醇难治性 CIP 的危险因素,并评估免疫调节剂(IM)的治疗策略。

方法

回顾性地确定了 2019 年 8 月至 2022 年 8 月期间接受程序性死亡(配体)-1 抗体治疗的实体瘤患者中的 CIP 患者。收集了临床特征、外周血生物标志物和影像学图像。

结果

在接受程序性死亡(配体)-1 抗体治疗的 1209 例实体瘤患者中,有 28 例发生皮质类固醇难治性 CIP,38 例发生皮质类固醇反应性 CIP。皮质类固醇难治性 CIP 患者既往有间质性肺病(p=0.015)和 3-4 级(p<0.001)的比例更高。此外,皮质类固醇难治性患者的绝对中性粒细胞计数(ANC)、降钙素原更高,白蛋白更低(ANC,p=0.009;降钙素原,p=0.024;白蛋白,p=0.026)。多因素分析后,确诊时的 3-4 级和更高 ANC 被确认为皮质类固醇难治性 CIP 的独立危险因素(级别,p=0.001;ANC,p=0.046)。对于 2 级皮质类固醇难治性 CIP,额外使用 IM 并不影响预后(p=1.000)。然而,在 3-4 级皮质类固醇难治性 CIP 中,额外使用 IM 显著降低了恶化的风险(p=0.036)。

结论

确诊时外周血 ANC 分级 3-4 级及以上与皮质类固醇难治性 CIP 风险增加相关。使用额外的 IM 可改善 3-4 级皮质类固醇难治性 CIP 的预后。这些结果可为 CIP 管理决策提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ac/10254972/2927860504e7/jitc-2023-006982f01.jpg

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