Systematic Assessment of Risk of Fever in Solid Tumor Patients Treated With PD-1/PD-L1 Inhibitors: A Systematic Review and Meta-Analysis

Li, Hongmei; Xu, Dongmei; Wang, Wentao; Sun, Fengchao; Zhang, Shuisheng; Yang, Xiaowei; Tian, Yuan

doi:10.3389/fonc.2020.570080

Cited by 5 publications

(4 citation statements)

References 50 publications

(161 reference statements)

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“…The PRISMA flow diagram was shown in ( Figure 1 ), while the bias assessment summary of all enrolled clinical trials were provided in ( Supplementary Figure 1 ). A total of 589 published studies was found by PubMed search, while 37 studies were gotten from the former published meta-analysis ( 61 – 63 ). After eligibility assessment, 5 articles were only used for the systematic review ( 13 , 20 – 23 ), while 42 articles were used for the final comprehensive analysis ( 4 – 12 , 14 – 19 , 24 – 50 ).…”

Section: Resultsmentioning

confidence: 99%

The Risk of Immune-Related Thyroid Dysfunction Induced by PD-1/PD-L1 Inhibitors in Cancer Patients: An Updated Systematic Review and Meta-Analysis

Tian

Liu

et al. 2021

Front. Oncol.

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BackgroundThyroid dysfunction is common for cancer patients receiving PD-1/PD-L1 inhibitor therapies. To clarify the incidence risk of thyroid dysfunction would be important for guiding anti-PD-1 and anti-PD-L1 immunotherapy. Therefore, the updated meta-analysis was conducted to evaluate the incidence risk of thyroid dysfunction caused by PD-1/PD-L1 inhibitors.MethodsPD-1/PD-L1 inhibitor related clinical trials were collected by a systematic search of the PubMed. Some relevant studies were identified by a manual search. The incidence risk of all grades and grades 3-5 was analyzed and evaluated by random effect model. The Newcastle Ottawa Scale was used for the quality assessment of all clinical trials.ResultsForty-three clinical trials were collected. Compared with chemotherapy, the risk of hypothyroidism of all grades was significantly higher (OR=7.15, 95%CI:[4.85, 10.55], I2 = 40%, Z=9.91(P <0.00001)) in PD-1/PD-L1 group. Similar results could also be noted, when the control group was placebo or CTLA-4. When PD-1/PD-L1 was combined with other treatments for cancer patients, the risk of hypothyroidism of all grades was also significantly increased. Similar to the analysis results of hypothyroidism, PD-1/PD-L1 inhibitors played the same role in increasing the risk of hyperthyroidism and thyroiditis. Few significant analysis results was noted, when the risk of thyroid dysfunction of grades 3-5 was assessed.ConclusionWhether used alone or in combination with other anti-tumor drugs, PD-1/PD-L1 inhibitors increased the risk of thyroid dysfunction, especially for hypothyroidism. Furthermore, PD-1/PD-L1 was better than chemotherapy and CTLA-4 in increasing the risk of thyroid dysfunction.

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Section: Resultsmentioning

confidence: 99%

The Risk of Immune-Related Thyroid Dysfunction Induced by PD-1/PD-L1 Inhibitors in Cancer Patients: An Updated Systematic Review and Meta-Analysis

Tian

Liu

et al. 2021

Front. Oncol.

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“…This mechanism will increase the activity and mobility of leukocytes, stimulate the production of interferon, and activate T cells to enhance immune response (5). The immune checkpoints involved in T cell activation, PDCD1 and CTLA4 are associated with the mechanism of fever (6).Moreover, Tritto et al (7) hypothesized that the injectionsite reaction was due to the use of adjuvants. The adjuvant provides the second signal that is necessary for T cell activation and increases the release of cytokines and chemokines; hence, immune cells in the blood will gather at the injection site, leading to redness, swelling and pain (8).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association between the side effect induced by COVID-19 vaccines and the immune regulatory gene polymorphism

Chen

Wen²,

Lin³

et al. 2022

Front. Immunol.

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People often worry about the side effects after vaccination, reducing the willingness to vaccinate. Thus, we tried to find out the risk of single nucleotide polymorphism (SNP) vaccines to improve the willingness and confidence in vaccination. Allergic and inflammatory reactions are the common vaccine side effects caused by immune system overreaction. In addition, a previous study showed significantly higher frequency of febrile reactions to measles vaccines in American Indians than in Caucasian children, indicating that the side effects varied in accordance with genetic polymorphisms in individuals. Thus, SNPs of immune regulatory genes, cytotoxic T-lymphocyte-associated protein 4 (CTLA4), CD28, tumor necrosis factor ligand superfamily member 4 (TNFSF4) and programmed cell death protein 1 (PDCD1) were included in this study to analyze their association with vaccine side effects. Moreover, 61 healthy participants were asked on the number of doses they received, the brand of the vaccine, and the side effects they suffered. We found that several SNPs were associated with side effects after the first or second dose of mRNA or adenoviral vector vaccines. Furthermore, these SNPs were associated with several autoimmune diseases and cancer types; thus, they played an important role in immune regulation. Moreover, rs3181096 and rs3181098 of CD28, rs733618 and rs3087243 of CTLA, and rs1234314 of TNFSF4 were associated with mild vaccine side effects induced by mRNA and adenoviral vector vaccines, which would play a potential role in vaccine-induced immune responses and may further lead to fatal side effects. These results could serve as a basis for investigating the mechanism of vaccine side effects. Furthermore, it was hoped that these results would address public concerns about the side effects of the COVID-19 vaccination. In clinical application, a rapid screening test can be performed to assess the risk of vaccine side effects before vaccination and provide immediate treatment.

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“…On the basis of research into the mechanisms of immune escape, PD-1 or PD-L1 inhibitors have reshaped the therapy landscape for cancer by activating the immune system, while also gradually reporting plenty of treatment-related side effects [3]. Although the association between some adverse events and PD-1 or PD-L1 inhibitors has been extensively examined and documented [4][5][6][7][8][9], many toxicities remain unexplored, including skin toxicities [3].…”

Section: Introductionmentioning

confidence: 99%

Risk of Rash in PD-1 or PD-L1-Related Cancer Clinical Trials: A Systematic Review and Meta-Analysis

Tian¹,

Zhang

Dang

et al. 2022

Journal of Oncology

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Background. Given that immune-related rash was the most frequently reported PD-1 or PD-L1-related skin toxicity, this systematic review and meta-analysis were conducted to elucidate its incidence risk. Methods. The meta-analysis was carried out according to the PRISMA guidelines. The random effect model was used in the process of all analyses. Skin rash of all grades and grades 3–5 were calculated and gathered in the final comprehensive analyses. Results. The study included 86 clinical trials classified into 15 groups. Compared with chemotherapy, PD-1 or PD-L1 inhibitors significantly strengthened the risk of developing rash across all grades (OR = 1.66, 95% CI: [1.31, 2.11]; p < 0.0001 ). This trend was significantly stronger when the control group was placebo (OR = 2.62, 95% CI: [1.88, 3.65]; p < 0.00001 ). Similar results were observed when PD-1 or PD-L1 inhibitors were given together with chemotherapy (OR = 1.87, 95% CI: [1.59, 2.20]; p < 0.00001 ), even in patients with grades 3–5. As with other combination therapies, the risk of developing rash for all grades was enhanced when PD-1 or PD-L1 was given together with chemotherapy as the second-line option (OR = 2.98, 95% CI: [1.87, 4.75]; p = 0.05 ). No statistically significant differences could be found in skin rash between the PD-1 and PD-L1-related subgroups. Conclusion. Whether PD-1 or PD-L1 inhibitors were given alone or together with others, the risk of developing rash would be enhanced. Furthermore, the risk of developing rash appeared to be higher when PD-1 or PD-L1 inhibitors together with other antitumor drugs were given as the second-line options. No statistically significant results of developing rash between PD-1 and PD-L1 subgroups were obtained owing to the participation of PD-1 or PD-L1 inhibitors.

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Systematic Assessment of Risk of Fever in Solid Tumor Patients Treated With PD-1/PD-L1 Inhibitors: A Systematic Review and Meta-Analysis

Cited by 5 publications

References 50 publications

The Risk of Immune-Related Thyroid Dysfunction Induced by PD-1/PD-L1 Inhibitors in Cancer Patients: An Updated Systematic Review and Meta-Analysis

The Risk of Immune-Related Thyroid Dysfunction Induced by PD-1/PD-L1 Inhibitors in Cancer Patients: An Updated Systematic Review and Meta-Analysis

Association between the side effect induced by COVID-19 vaccines and the immune regulatory gene polymorphism

Risk of Rash in PD-1 or PD-L1-Related Cancer Clinical Trials: A Systematic Review and Meta-Analysis

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