Real-world safety and efficacy data of immunotherapy in patients with cancer and autoimmune disease: the experience of the Hellenic Cooperative Oncology Group
Abstract:Background
Data on the safety and efficacy of immune checkpoint inhibitors (ICI) in patients with concurrent autoimmune diseases (AID) are limited.
Methods
We performed a retrospective multicenter review of medical records of patients with cancer and underlying AID who received ICI. The primary endpoint was progression-free survival (PFS).
Results
Among 123 patients with pre-existing AID who received ICI, the majori… Show more
“…Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases, which comprises approximately 40–50% cases of lung adenocarcinoma (LUAD) and 20–30% cases of lung squamous cell carcinoma (LUSC) ( Liu et al, 2021 ; Siegel et al, 2020 ). Despite advances in chemoradiotherapy and targeted therapies, immune checkpoint inhibitors (ICI), including programmed death-ligand 1 (PD-L1), programmed cell death 1 (PD-1), and cytotoxic T lymphocyte antigen-4 (CTLA-4) represent promising advances in the treatment of lung cancer ( Hiley et al, 2016 ; Bhandari et al, 2021 ; Fountzilas et al, 2021 ); however, the clinical response rate of ICIs is only 20%, which can seriously hinder its wider application ( Borghaei et al, 2015 ; Brahmer et al, 2015 ; Reck et al, 2016 ; Rittmeyer et al, 2017 ).…”
Background: Lung cancer is the leading cause of cancer-related death globally. Hypoxia can suppress the activation of the tumor microenvironment (TME), which contributes to distant metastasis. However, the role of hypoxia-mediated TME in predicting the diagnosis and prognosis of lung adenocarcinoma (LUAD) patients remains unclear.Methods: Both RNA and clinical data from the LUAD cohort were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Both univariate and multivariate Cox regression analyses were used to further screen prognosis-related hypoxia gene clusters. Time-dependent receiver operation characteristic (ROC) curves were established to evaluate the predictive sensitivity and specificity of the hypoxia-related risk signature. The characterization of gene set enrichment analysis (GSEA) and TME immune cell infiltration were further explored to identify hypoxia-related immune infiltration.Results: Eight hypoxia-related genes (LDHA, DCN, PGK1, PFKP, FBP1, LOX, ENO3, and CXCR4) were identified and established to construct a hypoxia-related risk signature. The high-risk group showed a poor overall survival compared to that of the low-risk group in the TCGA and GSE68465 cohorts (p < 0.0001). The AUCs for 1-, 3-, and 5-year overall survival were 0.736 vs. 0.741, 0.656 vs. 0.737, and 0.628 vs. 0.649, respectively. The high-risk group was associated with immunosuppression in the TME.Conclusion: The hypoxia-related risk signature may represent an independent biomarker that can differentiate the characteristics of TME immune cell infiltration and predict the prognosis of LUAD.
“…Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases, which comprises approximately 40–50% cases of lung adenocarcinoma (LUAD) and 20–30% cases of lung squamous cell carcinoma (LUSC) ( Liu et al, 2021 ; Siegel et al, 2020 ). Despite advances in chemoradiotherapy and targeted therapies, immune checkpoint inhibitors (ICI), including programmed death-ligand 1 (PD-L1), programmed cell death 1 (PD-1), and cytotoxic T lymphocyte antigen-4 (CTLA-4) represent promising advances in the treatment of lung cancer ( Hiley et al, 2016 ; Bhandari et al, 2021 ; Fountzilas et al, 2021 ); however, the clinical response rate of ICIs is only 20%, which can seriously hinder its wider application ( Borghaei et al, 2015 ; Brahmer et al, 2015 ; Reck et al, 2016 ; Rittmeyer et al, 2017 ).…”
Background: Lung cancer is the leading cause of cancer-related death globally. Hypoxia can suppress the activation of the tumor microenvironment (TME), which contributes to distant metastasis. However, the role of hypoxia-mediated TME in predicting the diagnosis and prognosis of lung adenocarcinoma (LUAD) patients remains unclear.Methods: Both RNA and clinical data from the LUAD cohort were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Both univariate and multivariate Cox regression analyses were used to further screen prognosis-related hypoxia gene clusters. Time-dependent receiver operation characteristic (ROC) curves were established to evaluate the predictive sensitivity and specificity of the hypoxia-related risk signature. The characterization of gene set enrichment analysis (GSEA) and TME immune cell infiltration were further explored to identify hypoxia-related immune infiltration.Results: Eight hypoxia-related genes (LDHA, DCN, PGK1, PFKP, FBP1, LOX, ENO3, and CXCR4) were identified and established to construct a hypoxia-related risk signature. The high-risk group showed a poor overall survival compared to that of the low-risk group in the TCGA and GSE68465 cohorts (p < 0.0001). The AUCs for 1-, 3-, and 5-year overall survival were 0.736 vs. 0.741, 0.656 vs. 0.737, and 0.628 vs. 0.649, respectively. The high-risk group was associated with immunosuppression in the TME.Conclusion: The hypoxia-related risk signature may represent an independent biomarker that can differentiate the characteristics of TME immune cell infiltration and predict the prognosis of LUAD.
“…Monoclonal antibodies are now being in conjunction with other therapies and/or adjuvants. Some examples of recently concluded clinical trials are listed in Supplementary Table 2 [ 32 – 35 ]. Fig.…”
The immune system interacts with cancer cells in multiple intricate ways that can shield the host against hyper-proliferation but can also contribute to malignancy. Understanding the protective roles of the immune system in its interaction with cancer cells can help device new and alternate therapeutic strategies. Many immunotherapeutic methodologies, including adaptive cancer therapy, cancer peptide vaccines, monoclonal antibodies, and immune checkpoint treatment, have transformed the traditional cancer treatment landscape. However, many questions remain unaddressed. The development of personalized combination therapy and neoantigen-based cancer vaccines would be the avant-garde approach to cancer treatment. Desirable chemotherapy should be durable, safe, and target-specific. Managing both tumor (intrinsic factors) and its microenvironment (extrinsic factors) are critical for successful immunotherapy. This review describes current approaches and their advancement related to monoclonal antibody-related clinical trials, new cytokine therapy, a checkpoint inhibitor, adoptive T cell therapy, cancer vaccine, and oncolytic virus.
Supplementary Information
The online version contains supplementary material available at 10.1007/s11033-022-07525-8.
“…Overall, the toxicities of ICI therapy were manageable. Outside of UC and RCC, there is also real world evidence that ICI therapy in those with pre-existing autoimmune conditions infrequently requires discontinuation due to irAEs [ 49 , 57 ].…”
Section: Management For Patients With Cancer and Iraesmentioning
Numerous immunotherapeutic agents, such as immune checkpoint inhibitors (ICIs), have been approved for the treatment of genitourinary (GU) malignancies. While ICIs have improved treatment outcomes and expanded treatment options, they can cause immune-related adverse events (irAEs). The scope of irAEs is broad, and this paper aims to review the rheumatologic side effects associated with immunotherapy drugs approved for bladder cancer and renal cell carcinoma. IrAEs are graded by the common terminology criteria for adverse events (CTCAE), which ranges from 1 to 5. The management of irAEs includes corticosteroids or other immunosuppressive therapies, and it may require discontinuation of immunotherapy. Several real world experience studies suggest that most patients with pre-existing autoimmune diseases treated with ICI did not have to discontinue treatment due to immune-mediated side effects. While data suggest autoimmune side effects are manageable, patients with pre-existing autoimmune diseases are often excluded from immunotherapy clinical trials. Better understanding of these irAEs will improve its safety and expand its use in those with underlying autoimmune disease.
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