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癌症和 COVID-19 患者的免疫抑制与免疫治疗相互作用。

Interplay of Immunosuppression and Immunotherapy Among Patients With Cancer and COVID-19.

机构信息

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Division of Hematology/Oncology, University of Cincinnati Cancer Center, Cincinnati, Ohio.

出版信息

JAMA Oncol. 2023 Jan 1;9(1):128-134. doi: 10.1001/jamaoncol.2022.5357.

Abstract

IMPORTANCE

Cytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation.

OBJECTIVE

To determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer.

DESIGN, SETTING, AND PARTICIPANTS: This registry-based retrospective cohort study included 12 046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings.

EXPOSURES

Immunosuppression due to therapy; systemic anticancer therapy (IO or non-IO).

MAIN OUTCOMES AND MEASURES

The primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm.

RESULTS

The median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79).

CONCLUSIONS AND RELEVANCE

This cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm.

TRIAL REGISTRATION

ClinicalTrials.gov Identifier: NCT04354701.

摘要

背景

COVID-19 引起的细胞因子风暴可导致高发病率和死亡率,并且在接受免疫疗法(IO)治疗的癌症患者中可能更为常见,这是由于免疫系统的激活。

目的

确定基线免疫抑制和/或基于 IO 的治疗与癌症患者 COVID-19 严重程度和细胞因子风暴的相关性。

设计、设置和参与者:这项基于登记的回顾性队列研究纳入了 2020 年 3 月至 2022 年 5 月期间向 COVID-19 和癌症联合会(CCC19)登记处报告的 12046 名患者。CCC19 登记处是一个集中的国际多机构登记处,登记了当前或过去患有 COVID-19 的癌症患者。分析的记录包括有活动期或既往癌症且经聚合酶链反应和/或血清学发现实验室确诊 SARS-CoV-2 感染的患者。

暴露因素

因治疗而导致的免疫抑制;全身抗癌治疗(IO 或非 IO)。

主要结果和措施

主要结局是 COVID-19 严重程度的 5 级有序量表:无并发症;住院但无需吸氧;住院且需要吸氧;入住重症监护病房和/或需要机械通气;死亡。次要结局是细胞因子风暴的发生。

结果

整个队列的中位年龄为 65 岁(四分位距 [IQR],54-74)岁,6359 名患者为女性(52.8%),6598 名(54.8%)为非西班牙裔白人。共有 599 名(5.0%)患者接受 IO,4327 名(35.9%)患者接受非 IO 全身抗癌治疗,7120 名(59.1%)患者在 COVID-19 诊断前 3 个月内未接受任何抗肿瘤方案。尽管在整个队列中,IO 组与未治疗组在 COVID-19 严重程度和细胞因子风暴方面没有差异(调整后的优势比 [aOR],0.80;95%CI,0.56-1.13 和 aOR,0.89;95%CI,0.41-1.93),但接受 IO 治疗且基线免疫抑制的患者(与未治疗相比)COVID-19 严重程度和细胞因子风暴更差(aOR,3.33;95%CI,1.38-8.01 和 aOR,4.41;95%CI,1.71-11.38)。接受非 IO 治疗且有免疫抑制的患者(与未治疗相比)COVID-19 严重程度(aOR,1.79;95%CI,1.36-2.35)和细胞因子风暴(aOR,2.32;95%CI,1.42-3.79)也更差。

结论和相关性

这项队列研究发现,在患有癌症和 COVID-19 的患者中,在基线免疫抑制的情况下,全身抗癌治疗,特别是 IO 的应用与严重的临床结局和细胞因子风暴的发生有关。

试验注册

ClinicalTrials.gov 标识符:NCT04354701。

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