Immune-checkpoint inhibitors for the treatment of metastatic melanoma: a model of cancer immunotherapy

Publication date: Available online 17 August 2019Source: Seminars in Cancer BiologyAuthor(s): Paola Queirolo, Andrea Boutros, Enrica Tanda, Francesco Spagnolo, Pietro QuaglinoAbstractMelanoma has always been described as an immunogenic tumor. Despite that, until 2011 the standard of care in metastatic melanoma was chemotherapy, with low response rates and no clear impact on overall survival. Melanoma was the first cancer type to drive the use of immune-checkpoint inhibitors into clinical practice, which revolutionized the therapeutic paradigm not only in melanoma, but also in an increasing number of tumors. In this review, the preclinical bases and the main clinical studies that led to the approval of immune-checkpoint inhibitors in advanced melanoma will be described with insights on novel combinations of treatments and on prognostic and predictive biomarkers.
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research

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This report describes a 21-year-old man who was refractory to chemotherapy and immunotherapy. Whole exome sequencing and low-depth whole genome sequencing confirmed the KRAS gene amplification, which may lead to the tumor cells' progression and proliferation. After discussion at the molecular tumor board, the patient was offered paclitaxel, carboplatin, and sorafenib (CPS) based on a phase III clinical trial of melanoma with KRAS gene copy gains. After treatment with CPS, the patient achieved excellent curative effects. Because of a nearly 50% frequency of KRAS amplification in chemotherapy-refractory testicular germ cells...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
Abstract CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 antibodies of varying formulations have been evaluated in the clinic and found to be tolerable and feasible. Administration is associated with mild to moderate (but transient) cytokine release syndrome, readily managed in the outpatient setting. Antitumor activity with or without anti-CTLA4 monoclonal antibody (mAb) therapy has been observed in patients with m...
Source: Annual Review of Medicine - Category: General Medicine Authors: Tags: Annu Rev Med Source Type: research
When TJ Sharpe was diagnosed with Stage 4 melanoma in August 2012, his future looked bleak. He was 37 years old with two young children, the median lifespan for patients with his diagnosis was 18 months and treatment options were limited.Thanks to some knowledge of the pharmaceutical industry he soon realised his best chance of survival was to find a clinical trial. It was a daunting prospect, but his resolve was solid and, after undergoing six surgical operations and four immunotherapy treatments across two different clinical trials, he lived to tell the tale.“I was lucky,” says Sharpe, “I was aware of c...
Source: EyeForPharma - Category: Pharmaceuticals Authors: Source Type: news
Publication date: Available online 9 August 2019Source: Seminars in Cancer BiologyAuthor(s): Monica Marzagalli, Nancy D. Ebelt, Edwin R. ManuelAbstractCutaneous melanoma is the most common skin cancer with an incidence that has been rapidly increasing in the past decades. Melanomas are among the most immunogenic tumors and, as such, have the greatest potential to respond favorably to immunotherapy. However, like many cancers, melanomas acquire various suppressive mechanisms, which generally act in concert, to escape innate and adaptive immune detection and destruction. Intense research into the cellular and molecular event...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
Purpose of review The aim of this review is to provide an overview of the current development of immuno-oncology in the (neo)adjuvant setting. Recent findings Several checkpoint inhibitors (CPis) have been approved for the treatment of advanced solid cancers, mostly for unresectable metastatic setting. Thus, the next logical step is to explore the potential of CPi in earlier stages of the disease. Summary There are currently many ongoing trials investigating immunotherapy agents in the early setting in various tumor types, involving various CPis and other innovative immunotherapies, as well as combinations with eit...
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: INNOVATIVE AGENTS AND TREATMENT MODALITIES: Edited by Ahmad Awada and Steven T. Rosen Source Type: research
Authors: Ingles Garces AH, Au L, Mason R, Thomas J, Larkin J Abstract Introduction: Immunotherapy has revolutionised the treatment of cancer. Given this growing success, at the same time, there are significant limitations and unanswered questions concerning response rates, duration of therapy, why some patients respond and others do not, and if combining different immune-agents would overcome this lack of response, increase the chance of success and postpone acquired resistance. Areas covered: The comprehension of how to properly modulate the immune pathways, the molecular and the immunological bases of the disease...
Source: Expert Opinion on Investigational Drugs - Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research
In this study, we investigated local (tumor) and peripheral (blood) cellular immunome of patients with melanoma, breast cancer and brain cancer using a rapid and reliable standardized, multiparameter flow cytometry assay. We used this approach to monitor changes in the peripheral cellular immunome in women with breast cancer undergoing SOC therapy. Our analysis is unique because it is conducted using matched fresh tumor tissue and blood from patients in real-time, within 2-3 hours of sample acquisition, and provides insight into the innate and adaptive immune cell profile in blood and tumor. Specific to blood, this approac...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Publication date: Available online 22 June 2019Source: Seminars in Cancer BiologyAuthor(s): Fabrizio Fontana, Michela Raimondi, Alessandro Di Domizio, Roberta M. Moretti, Marina Montagnani Marelli, Patrizia LimontaAbstractMelanoma is the most fatal form of skin cancer. Current therapeutic approaches include surgical resection, chemotherapy, targeted therapy and immunotherapy. However, these treatment strategies are associated with development of drug resistance and severe side effects. In recent years, natural compounds have also been extensively studied for their anti-melanoma effects, including tumor growth inhibition, a...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
In this report, we present a case of pembrolizumab-induced autoimmune hemolytic anemia and pancytopenia in a patient who was receiving pembrolizumab treatment for metastatic melanoma. This patient has a history of chronic lymphocytic leukemia and was diagnosed with metastatic melanoma in 2017. He developed symptomatic AIHA and pancytopenia after receiving 8 cycles of pembrolizumab in 2018. Pembrolizumab treatment was discontinued and he was treated with blood transfusion and prednisone. After 5 months of tapering prednisone treatment, his anemia and pancytopenia have improved toward successful recovery. Cancer patients alr...
Source: Case Reports in Oncology - Category: Cancer & Oncology Source Type: research
This study addressed a crucial public health priority by evaluating disparities in administration of immunotherapy for metastatic melanoma. The National Cancer Database was queried for newly diagnosed metastatic melanoma. Patients were dichotomized based on receipt of immunotherapy based on National Cancer Database coding. Multivariable logistic regression ascertained factors associated with immunotherapy delivery. Subgroup analysis evaluated the interaction between race, insurance status, and income. Secondarily, Cox multivariate and propensity-matched Kaplan-Meier analyses assessed overall survival based on immunotherapy...
Source: Journal of Immunotherapy - Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
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