Abstract

Background

There are fewer adverse events with immune checkpoint inhibitors (ICPI) than with chemotherapy, however, some patients receiving ICPI may require intensive care treatment in case of severe immune-related adverse events (IRAE’s), which should be immediately recognized to permit an appropriate treatment. We present data of patients admitted to The Royal Marsden Cancer Critical Care Unit (CCU) with IRAE’s. Our objective was also to determine if baseline inflammatory biomarkers (IB), such as LDH, neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR) and systemic inflammatory response index (SIRI) at admission could correlate with patient outcomes.

Methods

17 patients were identified between January 2012 and July 2019. Survival analysis was performed using Kaplan-Meier curves and Cox regression, using SPSS v24. All ratios were calculated with absolute counts of neutrophils, lymphocytes and monocytes. Best cut-off ratios were obtained using ROC curves.

Results

Most patients (88.2%; n = 15) had the diagnosis of metastatic melanoma. 6 patients were treated with ipilimumab, 3 with nivolumab, 7 with the combination of both and 1 patient with pembrolizumab. Median length of stay in the CCU was 4 days. The most common reason for admission was colitis in 47.1% (n = 8) of patients. Median overall survival (OS) from date of admission was 8.7 months. Outcome from CCU (stable discharge or long-term rehab) correlates with survival (R²=0.61). In the group of patients with LDH ≥ 189, OS was 1.4 months and in the group with LDH<189, OS was not yet reached (HR 0.28; p = 0.05). In the group with NLR ≥ 6.8, OS was 1.5 months and in the group of NLR<6.8, the median OS was 27.6 months (HR 0.34; p = 0.11).

Conclusion

It is likely that the number of critical care admissions may increase with more patients receiving ICPI. These events can be responsible for great morbidity which might be associated with increased mortality. IB such as high LDH, high NLR and high SIRI might correlate to poor outcome and worse survival and could be used to develop awareness of these events and a more effective approach. However, some of these results were not statistically significant and further studies are needed with a larger data to validate them.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

中文翻译：

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56P免疫相关不良事件入院患者重症监护结果的预测因素

抽象的

背景

与化学疗法相比，免疫检查点抑制剂（ICPI）的不良事件更少，但是，某些接受ICPI的患者在严重的免疫相关不良事件（IRAE's）的情况下可能需要重症监护，应立即意识到这一点，以便采取适当的治疗措施。我们提供了IRAE纳入皇家马斯登癌症重症监护室（CCU）的患者数据。我们的目的还在于确定入院时基线炎症生物标志物（IB），例如LDH，中性粒细胞与淋巴细胞之比（NLR），单核细胞与淋巴细胞之比（MLR）和全身炎症反应指数（SIRI）是否与患者预后相关。

方法

在2012年1月至2019年7月之间鉴定出17例患者。使用SPSS v24使用Kaplan-Meier曲线和Cox回归进行生存分析。所有比率均以嗜中性粒细胞，淋巴细胞和单核细胞的绝对计数计算。使用ROC曲线可获得最佳截止比。

结果

大多数患者（88.2％； n = 15）被诊断为转移性黑色素瘤。6例患者接受了ipilimumab治疗，3例接受了nivolumab治疗，7例同时接受了这两种治疗，1例患者接受了pembrolizumab治疗。在CCU的中位住院时间为4天。入院的最常见原因是47.1％（n = 8）的患者患有结肠炎。自入院之日起，中位总生存期（OS）为8.7个月。CCU的结果（稳定出院或长期康复）与生存率相关（R ² = 0.61）。LDH≥189的患者组的OS为1.4个月，而LDH <189的患者的OS尚未达到（HR 0.28； p = 0.05）。NLR≥6.8组的OS为1.5个月，NLR <6.8组的中位OS为27.6个月（HR 0.34； p = 0.11）。

结论

随着更多的患者接受ICPI，重症监护病房的数量可能会增加。这些事件可能是导致高发病率的原因，而高发病率可能与死亡率增加有关。高LDH，高NLR和高SIRI等IB可能与不良预后和较差的生存率相关，可用于增强对这些事件的认识和更有效的方法。但是，其中一些结果在统计上并不显着，需要进一步的研究以提供更大的数据来验证它们。

负责研究的法人实体

作者。

资金

尚未收到任何资金。

揭露

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