Influence of age and cancer history on prevalence of autoimmunity in patients with metastatic melanoma: A large retrospective study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22016-e22016
Author(s):  
Aaron N. Holmes ◽  
Xiaoyang Wang ◽  
Helen Swede ◽  
Upendra P. Hegde
Keyword(s):  
Metastatic Melanoma ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Survival Rates ◽  
Primary Melanoma ◽  
Study Groups ◽  
Cancer Type ◽  
Cancer History ◽  
Autoimmune Conditions ◽  
Cutaneous Cancer

e22016 Background: While immune checkpoint inhibitors (ICIs) have improved the survival rates of metastatic melanoma in recent years, immune-related adverse events (irAEs) remain a major toxicity. Studies have established that pre-existing autoimmunity increases the risk of severe irAEs following ICI therapy (1). Melanoma is common cancer in older patients, and older age is believed to be a risk factor of autoimmunity. However, there is controversy concerning the influence of age increasing the risk of irAEs between clinical trials, which exclude patients with confirmed or suspected autoimmunity, and less-selective but lower-power case reports (2). In order to understand potential irAE risk following ICI treatment, we measured the prevalence of pre-existing autoimmune disease by age and cancer type. Methods: We studied 293,938 patients aged 18-106 years old who were treated at the University of Connecticut Health Center between 2000 and 2018 using GE Centricity’s IDX database. Patients were organized into four study groups based on International Classifications of Diseases codes (ICD-9 and ICD-10), specifically primary melanoma and three comparisons groups: non-cutaneous neoplasms alone, melanoma with non-cutaneous neoplasms, and patients without cancer history. A list of 340 ICD codes corresponding to 105 autoimmune conditions were queried. Results: Non-cutaneous cancer, in the absence or presence of melanoma, was associated with a higher prevalence of autoimmunity (27.0%, 29.4%, respectively) compared to the rates in patients with melanoma alone and those without cancer history (11.1%, 8.7%, respectively, p < 0.05). In patients with both melanoma and non-cutaneous cancers, those with metastases had an 11.7% increase in autoimmune prevalence compared to patients without metastases (p < 0.0001), the largest metastasis-associated increase observed across all cancer groups. Lastly, a logistic regression demonstrated that age is weakly correlated with autoimmunity (r = 0.01, p < 0.0001). Conclusions: The findings suggest that a history of metastasis, non-cutaneous cancer, and advanced age are associated with a higher prevalence of pre-existing autoimmunity in melanoma patients. As ICIs are indicated for metastatic melanoma, our findings warrant future studies and careful risk assessment of autoimmunity in senior patients.

scholarly journals Association of Advanced Age and Cancer History With Autoimmune Disease in Melanoma Patients: A Cross-Sectional Study

2021 ◽  
Author(s):  
Aaron Holmes ◽  
Helen Swede ◽  
Wendy Feer ◽  
Dnna Pike ◽  
Xiaoyan Wang ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Age Groups ◽  
Study Groups ◽  
Cross Sectional Study ◽  
Advanced Age ◽  
Solid Cancer ◽  
Cross Sectional ◽  
Cancer History ◽  
Cancer Group ◽  
Cutaneous Cancer

Abstract Background: Immune-related adverse events (irAEs) are a major toxicity of immune checkpoint inhibitors. Studies have reported that pre-existing autoimmunity increases the risk of irAEs, but it remains unknown which clinical factors are linked to auto-immune disorders in cancer patients. This study aimed to evaluate if the prevalence of autoimmune diseases varied by specific cancer history and advanced age.Methods: Our cross-sectional medical record review consisted of 291,333 patients (age, ≥18 years) treated between 2000 and 2018. Patients were classified into four study groups (melanoma only, non-cutaneous solid cancer only, melanoma and non-cutaneous cancer, and no cancer history). Dependent variable was the presence of ≥1 autoimmune disorders based on 99 conditions using 317 ICD codes. Results: Non-cutaneous cancer, in the absence or presence of melanoma, was associated with a higher prevalence of autoimmunity (16.5%, 95% CI 16.1-16.9; 20.0%, 95% CI 18.3-21.7, respectively) compared to the rates in patients with melanoma only and those without cancer history (9.3%, 95% CI 8.6-10.0; 6.2%, 95% CI 6.1-6.3, respectively). Among patients with metastases at initial presentation, those in the melanoma and non-cutaneous cancer group had a prevalence of 24.0% (95% CI 20.1-27.9) compared to 19.1% (95% CI 17.2-21.0) in those without metastases. Multiple logistic regression demonstrated that patients > 75 years exhibited the highest odds of autoimmunity relative to other age groups, which age 18-34 as the referent (OR, 1.78, 95% CI 1.67-1.89). Conclusions: Among patients with melanoma, the greatest prevalence of autoimmunity occurred with advanced age and a history of non-cutaneous cancer.

scholarly journals Association of advanced age and cancer history with autoimmune disease in melanoma patients: a cross-sectional study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Aaron N. Holmes ◽  
Helen Swede ◽  
Wendy M. Feer ◽  
Donna Comins Pike ◽  
Xiaoyan Wang ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Age Groups ◽  
Study Groups ◽  
Cross Sectional Study ◽  
Advanced Age ◽  
Solid Cancer ◽  
Cross Sectional ◽  
Cancer History ◽  
Cancer Group ◽  
Cutaneous Cancer

Abstract Background Immune-related adverse events (irAEs) are a major toxicity of immune checkpoint inhibitors. Studies have reported that pre-existing autoimmunity increases the risk of irAEs, but it remains unknown which clinical factors are linked to auto-immune disorders in cancer patients. This study aimed to evaluate if the prevalence of autoimmune diseases varied by specific cancer history and advanced age. Methods Our cross-sectional medical record review consisted of 291,333 patients (age, ≥18 years) treated between 2000 and 2018. Patients were classified into four study groups (melanoma only, non-cutaneous solid cancer only, melanoma and non-cutaneous cancer, and no cancer history). Dependent variable was the presence of ≥1 autoimmune disorders based on 98 conditions using 317 ICD codes. Results Non-cutaneous cancer, in the absence or presence of melanoma, was associated with a higher prevalence of autoimmunity (16.5, 95% CI 16.1–16.9; 20.0, 95% CI 18.3–21.7, respectively) compared to the rates in patients with melanoma only and those without cancer history (9.3, 95% CI 8.6–10.0; 6.2, 95% CI 6.1–6.3, respectively). Among patients with metastases at initial presentation, those in the melanoma and non-cutaneous cancer group had a prevalence of 24.0% (95% CI 20.1–27.9) compared to 19.1% (95% CI 17.2–21.0) in those without metastases. Multiple logistic regression demonstrated that patients > 75 years exhibited the highest odds of autoimmunity relative to other age groups, with age 18–34 as the referent (OR, 1.78, 95% CI 1.67–1.89). Conclusions Among patients with melanoma, the greatest prevalence of autoimmunity occurred with advanced age and a history of non-cutaneous cancer.

scholarly journals Treatment of Advanced Metastatic Melanoma

2021 ◽  
pp. 2021164S
Author(s):  
Pietro Quaglino ◽  
Paolo Fava ◽  
Luca Tonella ◽  
Marco Rubatto ◽  
Simone Ribero ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Targeted Therapies ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Survival Rates ◽  
National Health System ◽  
Stage Iv ◽  
Daily Practice ◽  
Long Term Results ◽  
Melanoma Patients

The introduction in clinical practice of new drug compounds both targeted therapies anti-BRAF and checkpoint inhibitors have largely improved our potential to manage advanced metastatic melanoma patients. This has led to a significant improvement in terms of response rates and particularly in the overall survival (OS). The long-term results of trials with follow-up data of patients treated with targeted or immunotherapies reported median OS rates around 24 months, with 5-year survival rates around 35-40%. As to the drugs currently available and reimbursed by the Italian National Health System, 3 combinations of anti-BRAF/anti-MEK inhibitors are available (dabrafenib/trametinib, vemurafenib/cobimetinib and the most recently introduced encorafenib/binimetinib). As for checkpoint inhibitors, first line immunotherapy is represented by anti-PD1 blockers (nivolumab and pembrolizumab), whilst the anti-CTLA-4 ipilimumab can be used as second line immunotherapy. The decision-making factors that define the best treatment approach in stage IV patients with metastatic melanoma include the mutation pattern, performance status, high/low tumor load, brain metastases, progression pattern (low/fast), and availability of clinical trials. This review will analyze the current therapeutic tools adopted for the treatment of metastatic melanoma patients. It will then focus on the latest results obtained by novel treatments (checkpoint inhibitors and targeted therapies) which can be used in the clinical daily practice.

scholarly journals Treatment of BRAF-Mutated Metastatic Melanoma: Immunotherapy or Target Therapy?

2021 ◽  
Vol 79 (2) ◽  
pp. 103-111
Author(s):  
Ana Sofia Rodrigues ◽  
Ana Brinca
Keyword(s):  
Metastatic Melanoma ◽  
Checkpoint Inhibitors ◽  
Target Therapy ◽  
Survival Rates ◽  
Interleukin 2 ◽  
Braf Inhibitors ◽  
First Line ◽  
Braf Mutations ◽  
First Line Therapy ◽  
Line Therapy

Metastatic melanoma has been associated with a poor prognosis, with overall survival rates at 5 years of 10%. Until 2011, the only treatments available for metastatic melanoma were chemotherapy and immunotherapy with interleukin-2. The more in-depth knowledge about the molecular biology of melanoma and the identification of BRAF mutations, which are the most frequently found, allowed us to find new therapeutic targets that came to modify the prognosis of these patients. Currently, the treatments available for metastatic melanoma with BRAF mutation are immunotherapy with immunological checkpoint inhibitors (anti-PD-1 to anti-CTLA-4) and targeted therapy with BRAF inhibitors and MEK inhibitors. However, the first-line therapy to be instituted in these patients remains unknown.

scholarly journals Bullous Pemphigoid as an Adverse Reaction to Pembrolizumab: Two Case Reports

2018 ◽  
Vol 10 (2) ◽  
pp. 154-157 ◽  
Author(s):  
Kenneth Thomsen ◽  
Jon Diernaes ◽  
Trine Heide Øllegaard ◽  
Eva Spaun ◽  
Christian Vestergaard
Keyword(s):  
Adverse Reaction ◽  
Bullous Pemphigoid ◽  
Adverse Reactions ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Treatment Options ◽  
Survival Rates ◽  
Programmed Cell Death 1 ◽  
Different Types ◽  
Promising Treatment

Checkpoint inhibitors are novel and promising treatment options for different types of cancer. Programmed cell death 1 (PD-1) inhibitors, such as pembrolizumab, have been shown to significantly raise the survival rates of disseminated malignant melanoma (MM). Autoimmune adverse reactions are very common in checkpoint inhibitors. We present 2 cases of bullous pemphigoid, as adverse reactions to pembrolizumab-treated MM.

scholarly journals Durable Metastatic Melanoma Remission Following Pembrolizumab and Radiotherapy: A Case Report of Prophylactic Immunosuppression in a Patient with Myasthenia Gravis and Immune-Mediated Colitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Luke A. Moradi ◽  
Curtis A. Clark ◽  
Craig S. Schneider ◽  
Alok S. Deshane ◽  
Michael C. Dobelbower
Keyword(s):  
Myasthenia Gravis ◽  
Metastatic Melanoma ◽  
Tumor Regression ◽  
Checkpoint Inhibitors ◽  
Small Subset ◽  
Tumor Microenvironments ◽  
Mixed Response ◽  
Immune Mediated ◽  
Anti Cancer ◽  
Autoimmune Conditions

Immune checkpoint inhibitors (ICIs) and radiotherapy (RT) combinations for various metastatic cancers are increasingly utilized, yet the augmentation of anti-cancer immunity including distant tumor responses by RT remains ill-characterized. Immunosuppressive tumor microenvironments and defective anti-tumor immune activation including immune-related adverse events (irAEs) likely limit dramatic immuno-radiotherapy combinations, though it remains unclear which immune characteristics mediate dramatic systemic tumor regression in only a small subset of patients. Moreover, the efficacy of ICI treatment in patients receiving immunosuppressive therapies for autoimmune conditions or irAEs is convoluted, yet clinically valuable. Here, we report a case of a 75-year-old man with myasthenia gravis and metastatic melanoma who experienced complete and durable systemic regression after receiving pembrolizumab and single-lesion RT while on prednisone for myasthenia gravis prophylaxis and vedolizumab for immune-mediated colitis after previously experiencing mixed response on pembrolizumab monotherapy. We discuss the potential paradoxical effects and clinical considerations of immunosuppressive regimens in patients with underlying autoimmune disease or adverse immune reactions while receiving immuno-radiotherapy combinations.

scholarly journals Hemophagocytic Lymphohistiocytosis after Initiation of Combined Immunotherapy for Metastatic Melanoma

2021 ◽  
Vol 8 (4) ◽  
Author(s):  
Gambichler T ◽  
◽  
Rached NA ◽  
Nowack N ◽  
Behle B ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Checkpoint Inhibitors ◽  
Delayed Diagnosis ◽  
High Dose ◽  
Laboratory Findings ◽  
Case Presentation ◽  
Inappropriate Treatment ◽  
Autoimmune Conditions ◽  
Prompt Diagnosis

Hemophagocytic Lymphohistiocytosis (HLH), which is a severe, potentially fatal condition characterized by T lymphocyte overactivation, is predominantly caused by infections, hematological malignancies, and autoimmune conditions. HLH due to therapy with Immune Checkpoint Inhibitors (ICI) has rarely been reported. We describe a 60-year-old male with metastatic melanoma who developed HLH after the initiation of nivolumab plus ipilimumab treatment. Prompt diagnosis and high-dose mono-prednisolone therapy resulted in rapid resolution of his subjective symptoms and laboratory findings. Apart from this case presentation we provide a brief overview on clinical characteristics of previously observed ICI-induced HLH cases. Given the increasing use of ICI in a variety of cancers, the frequency of HLH will very likely raise. HLH morbidity and mortality are often the result of delayed diagnosis and inappropriate treatment. Hence, HLH must be considered in ICI-treated cancer patients who present with symptoms such as fever, cytopenias and hyperferritinemia.

Melanoma: Prognostic Factors and Factors Predictive of Response to Therapy

2020 ◽  
Vol 27 (17) ◽  
pp. 2792-2813
Author(s):  
Martina Strudel ◽  
Lucia Festino ◽  
Vito Vanella ◽  
Massimiliano Beretta ◽  
Francesco M. Marincola ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Lactate Dehydrogenase ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Elevated Serum ◽  
Predictive Biomarkers ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Prognostic Features ◽  
Programmed Death

Background: A better understanding of prognostic factors and biomarkers that predict response to treatment is required in order to further improve survival rates in patients with melanoma. Predictive Biomarkers: The most important histopathological factors prognostic of worse outcomes in melanoma are sentinel lymph node involvement, increased tumor thickness, ulceration and higher mitotic rate. Poorer survival may also be related to several clinical factors, including male gender, older age, axial location of the melanoma, elevated serum levels of lactate dehydrogenase and S100B. Predictive Biomarkers: Several biomarkers have been investigated as being predictive of response to melanoma therapies. For anti-Programmed Death-1(PD-1)/Programmed Death-Ligand 1 (PD-L1) checkpoint inhibitors, PD-L1 tumor expression was initially proposed to have a predictive role in response to anti-PD-1/PD-L1 treatment. However, patients without PD-L1 expression also have a survival benefit with anti-PD-1/PD-L1 therapy, meaning it cannot be used alone to select patients for treatment, in order to affirm that it could be considered a correlative, but not a predictive marker. A range of other factors have shown an association with treatment outcomes and offer potential as predictive biomarkers for immunotherapy, including immune infiltration, chemokine signatures, and tumor mutational load. However, none of these have been clinically validated as a factor for patient selection. For combined targeted therapy (BRAF and MEK inhibition), lactate dehydrogenase level and tumor burden seem to have a role in patient outcomes. Conclusions: With increasing knowledge, the understanding of melanoma stage-specific prognostic features should further improve. Moreover, ongoing trials should provide increasing evidence on the best use of biomarkers to help select the most appropriate patients for tailored treatment with immunotherapies and targeted therapies.

scholarly journals Monoclonal Antibody-Based Immunotherapy and Its Role in the Development of Cardiac Toxicity

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 86
Author(s):  
Mohit Kumar ◽  
Chellappagounder Thangavel ◽  
Richard C. Becker ◽  
Sakthivel Sadayappan
Keyword(s):  
Cancer Patients ◽  
Immune Modulation ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Induced Pluripotent Stem Cell ◽  
High Volume ◽  
Oncolytic Viruses ◽  
Model Systems ◽  
Volume Data ◽  
Late Cardiotoxicity

Immunotherapy is one of the most effective therapeutic options for cancer patients. Five specific classes of immunotherapies, which includes cell-based chimeric antigenic receptor T-cells, checkpoint inhibitors, cancer vaccines, antibody-based targeted therapies, and oncolytic viruses. Immunotherapies can improve survival rates among cancer patients. At the same time, however, they can cause inflammation and promote adverse cardiac immune modulation and cardiac failure among some cancer patients as late as five to ten years following immunotherapy. In this review, we discuss cardiotoxicity associated with immunotherapy. We also propose using human-induced pluripotent stem cell-derived cardiomyocytes/ cardiac-stromal progenitor cells and cardiac organoid cultures as innovative experimental model systems to (1) mimic clinical treatment, resulting in reproducible data, and (2) promote the identification of immunotherapy-induced biomarkers of both early and late cardiotoxicity. Finally, we introduce the integration of omics-derived high-volume data and cardiac biology as a pathway toward the discovery of new and efficient non-toxic immunotherapy.

scholarly journals Gastrointestinal Stromal Tumors (GISTs): Novel Therapeutic Strategies with Immunotherapy and Small Molecules

2021 ◽  
Vol 22 (2) ◽  
pp. 493
Author(s):  
Christos Vallilas ◽  
Panagiotis Sarantis ◽  
Anastasios Kyriazoglou ◽  
Evangelos Koustas ◽  
Stamatios Theocharis ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Gastrointestinal Stromal Tumors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Cancer Therapeutics ◽  
Gastrointestinal Neoplasms ◽  
Mesenchymal Tumors ◽  
Stromal Tumors

Gastrointestinal stromal tumors (GISTs) are the most common types of malignant mesenchymal tumors in the gastrointestinal tract, with an estimated incidence of 1.5/100.000 per year and 1–2% of gastrointestinal neoplasms. About 75–80% of patients have mutations in the KIT gene in exons 9, 11, 13, 14, 17, and 5–10% of patients have mutations in the platelet-derived growth factor receptor a (PDGFRA) gene in exons 12, 14, 18. Moreover, 10–15% of patients have no mutations and are classified as wild type GIST. The treatment for metastatic or unresectable GISTs includes imatinib, sunitinib, and regorafenib. So far, GIST therapies have raised great expectations and offered patients a better quality of life, but increased pharmacological resistance to tyrosine kinase inhibitors is often observed. New treatment options have emerged, with ripretinib, avapritinib, and cabozantinib getting approvals for these tumors. Nowadays, immune checkpoint inhibitors form a new landscape in cancer therapeutics and have already shown remarkable responses in various tumors. Studies in melanoma, non-small-cell lung cancer, and renal cell carcinoma are very encouraging as these inhibitors have increased survival rates. The purpose of this review is to present alternative approaches for the treatment of the GIST patients, such as combinations of immunotherapy and novel inhibitors with traditional therapies (tyrosine kinase inhibitors).

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