Immune checkpoints in thymic epithelial tumors: challenges and opportunities

Girard, Nicolas

doi:10.1016/j.iotech.2019.09.002

Cited by 10 publications

(3 citation statements)

References 60 publications

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“…However, PD-L1 rates in thymomas and thymic carcinomas have not exactly defined. 13 Higuchi et al. reported results of 39 patients with thymic tumor.…”

Section: Discussionmentioning

confidence: 99%

Nivolumab treatment for metastatic thymic epithelial tumors

Aydıner

2020

J Oncol Pharm Pract

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Background Metastatic and unresectable thymoma (T) or thymic carcinoma (TC) have limited treatment options, especially after first line. Methods Patients with unresectable or recurrent thymic tumors who used minimum one dose of nivolumab at any line of treatment were evaluated retrospectively. Even though nivolumab was administered 3mg/kg dosage in PRIMER study, due to toxicity and financial concerns, we used low dose regimen mostly. Results Among 46 unresectable and recurrent thymic epithelial tumors; 8 patients with TC (n = 3), T (n = 4) and mixt histology (n = 1) were reviewed. Three patients had myasthenia gravis history that had to be controlled before treatment. Four patients showed moderate (n = 2) or severe (n = 2) adverse events with nivolumab treatment. Interestingly, two severe adverse events were occurred at first dose even with 40 mg nivolumab and required cessation of treatment permanently. The median number of nivolumab received was four (range: 1–18). Best response was partial response. Two patients progressed at the 3rd and 5th month of treatment. Best duration of response for one patient with TC and one patient with T–B2 were 9 and 14 months, respectively. Median survival time after nivolumab was 7.4 months (range: 2–22.1). Conclusions After the results of the previous study could be supported by randomized prospective studies with more number of patients, nivolumab may be considered as an option in patients with thymic epithelial tumors who have received multiple line treatments. However, given the high rate of severe toxicities, there is need to find out a reliable marker to prediction patients who will derive benefit or exhibit toxicity.

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“…However, PD-L1 rates in thymomas and thymic carcinomas have not exactly defined. 13 Higuchi et al. reported results of 39 patients with thymic tumor.…”

Section: Discussionmentioning

confidence: 99%

Nivolumab treatment for metastatic thymic epithelial tumors

Aydıner

2020

J Oncol Pharm Pract

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“…2 B). Additionally, some cytokines, chemokines produced by tumor cells that induce cross-reactions between tumor antigens and TSAs, and the structural similarities between them, which promote autoantibody production, are other proposed mechanisms to explain autoimmunity in TETs [ 25 , 26 ]. For instance, thymoma overexpresses mid-sized neurofilament gene, which shares sequences encoding acetylcholine receptors and titin epitopes and is often correlated with myasthenia gravis [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Immunotherapy of thymic epithelial tumors: molecular understandings and clinical perspectives

Gao

Wang

et al. 2023

Mol Cancer

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Immunotherapy has emerged to play a rapidly expanding role in the treatment of cancers. Currently, many clinical trials of therapeutic agents are on ongoing with majority of immune checkpoint inhibitors (ICIs) especially programmed death receptor 1 (PD-1) and its ligand 1 (PD-L1) inhibitors. PD-1 and PD-L1, two main immune checkpoints, are expressed at high levels in thymic epithelial tumors (TETs) and could be predictors of the progression and immunotherapeutic efficacy of TETs. However, despite inspiring efficacy reported in clinical trials and clinical practice, significantly higher incidence of immune-related adverse events (irAEs) than other tumors bring challenges to the administration of ICIs in TETs. To develop safe and effective immunotherapeutic patterns in TETs, understanding the clinical properties of patients, the cellular and molecular mechanisms of immunotherapy and irAEs occurrence are crucial. In this review, the progress of both basic and clinical research on immune checkpoints in TETs, the evidence of therapeutic efficacy and irAEs based on PD-1 /PD-L1 inhibitors in TETs treatment are discussed. Additionally, we highlighted the possible mechanisms underlying irAEs, prevention and management strategies, the insufficiency of current research and some worthy research insights. High PD-1/PD-L1 expression in TETs provides a rationale for ICI use. Completed clinical trials have shown an encouraging efficacy of ICIs, despite the high rate of irAEs. A deeper mechanism understanding at molecular level how ICIs function in TETs and why irAEs occur will help maximize the immunotherapeutic efficacy while minimizing irAEs risks in TET treatment to improve patient prognosis.

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“…2 Treatment with immune checkpoint inhibitors or cancer vaccines intended to stimulate the immune system can cause severe immunerelated adverse events (AEs) in 3% to 57% of patients. 2,7,8 This reactivity raises questions on the tolerability of other forms of immune stimulation, such as vaccination against coronavirus disease 2019 (COVID- 19), in patients with TETs.…”

Section: Introductionmentioning

confidence: 99%

Tolerability of Coronavirus Disease 2019 Vaccines, BNT162b2 and mRNA-1273, in Patients With Thymic Epithelial Tumors

Ballman

Swift

Mullenix

et al. 2021

JTO Clinical and Research Reports

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Introduction Defects in immunological self-tolerance result in an increased risk for development of autoimmune paraneoplastic diseases (AD) and immune-mediated toxicity in response to immune stimulation in individuals with thymic epithelial tumors (TETs). We conducted a survey to evaluate the tolerability of Covid-19 messenger RNA (mRNA) vaccines in patients with TETs, including individuals with pre-existing AD. Methods After reviewing published data on adverse events (AEs) associated with the BNT162b2 (Pfizer, Inc., and BioNTech) and mRNA-1273 (ModernaTX, Inc.) mRNA vaccines, we designed and administered a questionnaire to participants at three timepoints: after each dose of vaccination and one month following the final dose. Questions related to AD and use of immunosuppressive drugs were included. Descriptive statistics were used to analyze data and results were compared with previously described results related to the BNT162b2 and mRNA-1273 vaccines. Results From February 26 th and June 1 st , 2021, we administered the survey to 54 participants (median age: 58 years; thymoma: 33; pre-existing AD: 19). Common AEs included injection-site pain, fatigue, and headaches. There were no vaccination-related hospitalizations or deaths. Autoimmune flares occurred in three (16%) patients after the first dose and three (17%) patients after the second dose. The majority of AD flares were mild and self-limited. One patient (2%) was diagnosed with a new AD following vaccination. Conclusions Tolerability of COVID-19 mRNA vaccines in patients with TETs is comparable to the general population. Most patients with pre-existing AD did not experience disease flares and the development of new AD was rare. Patients with TETs should be encouraged to get vaccinated against COVID-19 due to the documented benefits of vaccination and manageable risk profile.

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Immune checkpoints in thymic epithelial tumors: challenges and opportunities

Cited by 10 publications

References 60 publications

Nivolumab treatment for metastatic thymic epithelial tumors

Nivolumab treatment for metastatic thymic epithelial tumors

Immunotherapy of thymic epithelial tumors: molecular understandings and clinical perspectives

Tolerability of Coronavirus Disease 2019 Vaccines, BNT162b2 and mRNA-1273, in Patients With Thymic Epithelial Tumors

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