Immune Checkpoint Inhibitors Use and Effects on Prognosis of COVID-19 Infection: A Systematic Review and Meta-Analysis

Qian, Wenwei; Ye, Ying; Zuo, Lugen; Song, Ting; Xu, Qing; Wang, Yinghong; Qian, Jun; Tian, Yun

doi:10.2217/imt-2021-0007

Cited by 14 publications

(11 citation statements)

References 52 publications

(104 reference statements)

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“…While eight other published systematic reviews have examined IT in this patient group, the present one has notable strengths: it is the most recent study; it included three to four times the number of reports in the final analysis of mortality and severe events; it examined two times the number of published studies with adjusted outcome data and almost five times the number of studies with ICI patients alone (Supplementary‐Table 5). 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 Unfortunately, GRADE analysis demonstrated that even with this increasing body of data the certainty of evidence regarding the effects of ICIs in cancer patients with COVID‐19 is very low.…”

Section: Discussionmentioning

confidence: 99%

“… 16 , 17 , 18 , 19 While an ideal study examining the impact of ICIs on COVID‐19 outcomes would adjust for these variables and a systematic review addressing this question would focus on such adjusted studies, this has generally not been the case. 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 Among eight published systematic reviews of studies investigating cancer patients presenting with COVID‐19 that previously received immunotherapies (IT) including ICIs, only 3 provided analyses of adjusted outcomes with IT, and each of these was based on five or fewer published studies. 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 Furthermore, only two of these systematic reviews specifically differentiated between ICIs and non‐ICI ITs.…”

Section: Introductionmentioning

confidence: 99%

“… 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 Among eight published systematic reviews of studies investigating cancer patients presenting with COVID‐19 that previously received immunotherapies (IT) including ICIs, only 3 provided analyses of adjusted outcomes with IT, and each of these was based on five or fewer published studies. 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 Furthermore, only two of these systematic reviews specifically differentiated between ICIs and non‐ICI ITs. 26 , 27 This distinction is essential since ICIs have different mechanisms of action and biologic effects than non‐ICI ITs and in two recent studies, <10% of patients reportedly receiving ITs had received ICIs.…”

Section: Introductionmentioning

confidence: 99%

“… 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 Furthermore, only two of these systematic reviews specifically differentiated between ICIs and non‐ICI ITs. 26 , 27 This distinction is essential since ICIs have different mechanisms of action and biologic effects than non‐ICI ITs and in two recent studies, <10% of patients reportedly receiving ITs had received ICIs. 28 , 29 Of note, despite the rapidly increasing number of reports providing data on prior ICI treatment in cancer patients presenting with COVID‐19, the two systematic reviews available so far examining this question included only 10 and 13 published reports respectively.…”

Section: Introductionmentioning

confidence: 99%

“… 28 , 29 Of note, despite the rapidly increasing number of reports providing data on prior ICI treatment in cancer patients presenting with COVID‐19, the two systematic reviews available so far examining this question included only 10 and 13 published reports respectively. 26 , 27 Therefore, the primary purpose of our systematic review was to analyse studies presenting the adjusted effects specifically of ICI therapy on either survival, a severe event, or need for hospitalisation in cancer patients presenting with COVID‐19.…”

Section: Introductionmentioning

confidence: 99%

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Comprehensive adjusted outcome data are needed to assess the impact of immune checkpoint inhibitors in cancer patients with COVID‐19: Results of a systematic review and meta‐analysis

Minkove

Sun

et al. 2022

Reviews in Medical Virology

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Background Determining how prior immune checkpoint inhibitor (ICI) therapy influences outcomes in cancer patients presenting with COVID‐19 is essential for patient management but must account for confounding variables. Methods We performed a systematic review and meta‐analysis of studies reporting adjusted effects of ICIs on survival, severe events, or hospitalisation in cancer patients with COVID‐19 based on variables including age, gender, diabetes mellitus, hypertension (HTN), chronic obstructive pulmonary disease, and other comorbidities. When adjusted effects were unavailable, unadjusted data were analysed. Results Of 42 observational studies (38 retrospective), 7 reported adjusted outcomes for ICIs and 2 provided sufficient individual patient data to calculate adjusted outcomes. In eight studies, adjusted outcomes were based on ≤7 variables. Over all studies, only one included >100 ICI patients while 26 included <10. ICIs did not alter the odds ratio (95%CI) (OR) of death significantly (random effects model), across adjusted ( n = 8) [1.31 (0.58–2.95) p = 0.46; I 2 = 42%, p = 0.10], unadjusted ( n = 30) [1.06 (0.85–1.32) p = 0.58; I 2 = 0%, p = 0.76] or combined [1.09 (0.88;1.36) p = 0.41; I 2 = 0%, p = 0.5)] studies. Similarly, ICIs did not alter severe events significantly across adjusted ( n = 5) [1.20 (0.30–4.74) p = 0.73; I 2 = 52%, p = 0.08], unadjusted ( n = 19) [(1.23 (0.87–1.75) p = 0.23; I 2 = 16%, p = 0.26] or combined [1.26 (0.90–1.77) p = 0.16; I 2 = 25%, p = 0.14] studies. Two studies provided adjusted hospitalisation data and when combined with 13 unadjusted studies, ICIs did not alter hospitalisation significantly [1.19 (0.85–1.68) p = 029; I 2 = 5%, p = 0.40]. Results of sensitivity analyses examining ICI effects based on 5 variables were inconclusive. Certainty of evidence was very low. Conclusions Across studies with adjusted and unadjusted results, ICIs did not alter outcomes significantly. But studies with comprehensive adjusted outcome data controlling for confounding variables are necessary to determine whether ICIs impact COVID‐19 outcomes in cancer patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Comprehensive adjusted outcome data are needed to assess the impact of immune checkpoint inhibitors in cancer patients with COVID‐19: Results of a systematic review and meta‐analysis

Minkove

Sun

et al. 2022

Reviews in Medical Virology

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A Review of RRx-001: A Late-Stage Multi-Indication Inhibitor of NLRP3 Activation and Chronic Inflammation

Jayabalan

Oronsky

Cabrales

et al. 2023

Drugs

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Chronic unresolving inflammation is emerging as a key underlying pathological feature of many if not most diseases ranging from autoimmune conditions to cardiometabolic and neurological disorders. Dysregulated immune and inflammasome activation is thought to be the central driver of unresolving inflammation, which in some ways provides a unified theory of disease pathology and progression. Inflammasomes are a group of large cytosolic protein complexes that, in response to infection- or stress-associated stimuli, oligomerize and assemble to generate a platform for driving inflammation. This occurs through proteolytic activation of caspase-1-mediated inflammatory responses, including cleavage and secretion of the proinflammatory cytokines interleukin (IL)-1β and IL-18, and initiation of pyroptosis, an inflammatory form of cell death. Several inflammasomes have been characterized. The most well-studied is the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome, so named because the NLRP3 protein in the complex, which is primarily present in immune and inflammatory cells following activation by inflammatory stimuli, belongs to the family of nucleotide-binding and oligomerization domain (Nod) receptor proteins. Several NLRP3 inflammasome inhibitors are in development, all with multi-indication activity. This review discusses the current status, known mechanisms of action, and disease-modifying therapeutic potential of RRx-001, a direct NLRP3 inflammasome inhibitor under investigation in several late-stage anticancer clinical trials, including a phase 3 trial for the treatment of third-line and beyond small cell lung cancer (SCLC), an indication with no treatment, in which RRx-001 is combined with reintroduced chemotherapy from the first line, carboplatin/cisplatin and etoposide (ClinicalTrials.gov Identifier: NCT03699956). Studies from multiple independent groups have now confirmed that RRx-001 is safe and well tolerated in humans. Additionally, emerging evidence in preclinical animal models suggests that RRx-001 could be effective in a wide range of diseases where immune and inflammasome activation drives disease pathology.

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COVID-19 Outcomes in Stage IV Cancer Patients Receiving Immune Checkpoint Inhibitors

Guo

Liu

Zhou

et al. 2022

SN Compr. Clin. Med.

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Cancer patients are a vulnerable population in the current coronavirus disease 2019 (COVID-19) outbreak. The impact of immune checkpoint inhibitors (ICIs) on the outcomes of COVID-19 infection in cancer patients remains largely unclear. We retrospectively investigated all solid cancer patients who received at least one cycle of ICIs at a single institution between August 2020 and August 2021. All stage IV solid cancer patients who were on or ceased ICI treatment when diagnosed with COVID-19 were eligible. All COVID-19 infections were confirmed by RT-PCR. Risk factors for hospitalization, severe symptoms, and death were analyzed. A total of 56 patients were included in our study. Twenty (35.7%) patients require hospitalization, 12 (21.4%) developed severe symptoms, and 10 (17.9%) died from COVID-19 infection. ICI treatment was interrupted in 37 patients (66.1%), 24 of whom (64.9%) had treatment resumed. Eight (80%) COVID-19-related death occurred in unvaccinated individuals. Reinfection occurred in seven patients (12.5%), and three of them died from their second COVID-19 infection. Factors associated with hospitalization were high Charlson comorbidity score (OR 1.56, 95% CI 1.10-2.23, p = 0.01) and lymphocyte ≤ 1500 mm 3 (OR 10.05, 95% CI 2.03-49.85, p = 0.005). Age, chemoimmunotherapy, and ICI treatment duration were not associated with increased risk of hospitalization, severe symptoms, or COVID-19-related mortality. ICI therapy does not impose an increased risk for severe COVID-19 infection in stage IV cancer patients. Vaccination should be encouraged among this population. Clinicians should be cognizant of a potential worse outcome in COVID-19-reinfected patients.

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Immune Checkpoint Inhibitors Use and Effects on Prognosis of COVID-19 Infection: A Systematic Review and Meta-Analysis

Cited by 14 publications

References 52 publications

Comprehensive adjusted outcome data are needed to assess the impact of immune checkpoint inhibitors in cancer patients with COVID‐19: Results of a systematic review and meta‐analysis

Comprehensive adjusted outcome data are needed to assess the impact of immune checkpoint inhibitors in cancer patients with COVID‐19: Results of a systematic review and meta‐analysis

A Review of RRx-001: A Late-Stage Multi-Indication Inhibitor of NLRP3 Activation and Chronic Inflammation

COVID-19 Outcomes in Stage IV Cancer Patients Receiving Immune Checkpoint Inhibitors

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