Impact of cemiplimab treatment duration on clinical outcomes in advanced cutaneous squamous cell carcinoma.

Treatment duration with checkpoint inhibitors must be optimized to prevent unjustified toxicity, but evidence for the management of cutaneous squamous cell carcinoma is lacking. A retrospective study was performed to evaluate the survival of patients with cutaneous squamous cell carcinoma (CSCC) who discontinued cemiplimab due to different causes and without progression. Among 95 patients with CSCC who received cemiplimab, 22 (23%) patients discontinued immunotherapy due to causes other than progression, such as comorbidities, toxicity, complete response or lack of compliance (group that discontinued before censoring [DBC]), then 73 patients had standard treatment scheduled (STS).

Dabrafenib plus trametinib versus anti-PD-1 monotherapy as adjuvant therapy in V600-mutant stage III melanoma after definitive surgery: a multicenter, retrospective cohort study.

Background: Both dabrafenib/trametinib (D/T) and anti-PD-1 monotherapy (PD-1) are approved adjuvant therapies for patients with stage III V600-mutant melanoma. However, there is still a lack of head-to-head comparative data. We aimed to describe efficacy and toxicity outcomes for these two standard therapies across melanoma centers.

Potential clinical implications of CD4CD26 T cells for nivolumab treated melanoma patients.

Background: Nivolumab is an anti-PD1 antibody that has dramatically improved metastatic melanoma patients' outcomes. Nevertheless, many patients are resistant to PD-1 inhibition, occasionally experiencing severe off-target immune toxicity. In addition, no robust and reproducible biomarkers have yet been validated to identify the correct selection of patients who will benefit from anti-PD-1 treatment avoiding unwanted side effects.

Safety of extended interval dosing immune checkpoint inhibitors: a multicenter cohort study.

Background: Real-life spectrum and survival implications of immune-related adverse events (irAEs) in patients treated with extended interval dosing (ED) immune checkpoint inhibitors (ICIs) are unknown.

Methods: Characteristics of 812 consecutive solid cancer patients who received at least 1 cycle of ED monotherapy (pembrolizumab 400 mg Q6W or nivolumab 480 mg Q4W) after switching from canonical interval dosing (CD; pembrolizumab 200 mg Q3W or nivolumab 240 mg Q2W) or treated upfront with ED were retrieved. The primary objective was to compare irAEs patterns within the same population (before and after switch to ED).

IL-6 as new prognostic factor in patients with advanced cutaneous squamous cell carcinoma treated with cemiplimab.

Background: Prognostic factors for initial response of advanced cutaneous squamous cell carcinoma to cemiplimab treatment are lacking. Il-6 has been found to affect immune cell populations which impact tumor development. The aim was to investigate the prognostic significance of IL-6 serum levels before and during treatment.

Nivolumab serum concentration in metastatic melanoma patients could be related to outcome and enhanced immune activity: a gene profiling retrospective analysis.

Background: Nivolumab is an anti-PD-1 antibody approved for treating metastatic melanoma (MM), for which still limited evidence is available on the correlation between drug exposure and patient outcomes.

Methods: In this observational retrospective study, we assessed whether nivolumab concentration is associated with treatment response in 88 patients with MM and if the patient's genetic profile plays a role in this association.

Results: We observed a statistically significant correlation between nivolumab serum concentration and clinical outcomes, measured as overall and progression-free survival.

PD-L1 neutrophils as novel biomarkers for stage IV melanoma patients treated with nivolumab.

Melanoma displays a rising incidence, and the mortality associated with metastatic form remains high. Monoclonal antibodies that block programmed death (PD-1) and PD Ligand 1 (PD-L1) network have revolutionized the history of metastatic disease. PD-L1 is expressed on several immune cells and can be also expressed on human neutrophils (PMNs).

Management of cutaneous melanoma: radiologists challenging and risk assessment.

Melanoma patient remains a challenging for the radiologist, due to the difficulty related to the management of a patient more often in an advanced stage of the disease. It is necessary to determine a stratification of risk, optimizing the means, with diagnostic tools that should be optimized in relation to the type of patient, and improving knowledge. Staging and risk assessment procedures are determined by disease presentation at diagnosis.

Dermatologic adverse events associated with targeted therapies for melanoma.

Introduction: The development of new targeted therapies has considerably changed the therapeutic paradigm of melanoma, significantly increasing overall survival (OS) and progression-free survival (PFS). However, skin-related adverse sequelae might occur and impact on patients' quality of life.

Areas Covered: In this article we will cover the most important dermatological toxicities related to BRAF and MEK-inhibitors, along with updated management strategies.

Clinical Outcome Prediction in COVID-19 Patients by Lymphocyte Subsets Analysis and Monocytes' iTNF-α Expression.

In December 2019, a novel coronavirus, "SARS-CoV-2", was recognized as the cause of coronavirus disease 2019 (COVID-19). Several studies have explored the changes and the role of inflammatory cells and cytokines in the immunopathogenesis of the disease, but until today, the results have been controversial. Based on these premises, we conducted a retrospective assessment of monocyte intracellular TNF-α expression (iTNF-α) and on the frequencies of lymphocyte sub-populations in twenty-five patients with moderate/severe COVID-19.

Clinical Categorization Algorithm (CLICAL) and Machine Learning Approach (SRF-CLICAL) to Predict Clinical Benefit to Immunotherapy in Metastatic Melanoma Patients: Real-World Evidence from the Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy.

The real-life application of immune checkpoint inhibitors (ICIs) may yield different outcomes compared to the benefit presented in clinical trials. For this reason, there is a need to define the group of patients that may benefit from treatment. We retrospectively investigated 578 metastatic melanoma patients treated with ICIs at the Istituto Nazionale Tumori IRCCS Fondazione "G.

Ipilimumab and Stereotactic Radiosurgery with CyberKnife System in Melanoma Brain Metastases: A Retrospective Monoinstitutional Experience.

The median overall survival (OS) and local control (LC) of patients with melanoma brain metastases (MBMs) are poor even with immune checkpoint inhibitors and/or radiotherapy (RT). The aims of the study were to evaluate the association and timing of stereotactic radiotherapy (SRT)/radiosurgery (SRS) performed with the CyberKnife System and ipilimumab (IPI). A total of 63 MBMs patients were analyzed: 53 received RT+IPI and 10 RT alone.

Sustainable responses in metastatic melanoma patients with and without brain metastases after elective discontinuation of anti-PD1-based immunotherapy due to complete response.

Background: Anti-PD1-based immunotherapy is currently used in most patients with advanced melanoma. Despite the remarkable data regarding overall survival, the optimal treatment duration is still unknown.

Methods: We evaluated the outcome of 125 patients with advanced melanoma with and without brain metastases (MBM), treated either with anti-PD1 monotherapy (N = 97) or combined with anti-CTLA4 (N = 28) after elective treatment discontinuation due to complete response (CR) (group A, N = 86), or treatment-limiting toxicity (N = 33) and investigator's decision (ID, N = 6) (group B) with subsequent CR.

Emerging PD-1/PD-L1 antagonists for the treatment of malignant melanoma.

Introduction: Increased understanding of the interactive mechanisms between tumors and the immune system led to the development of immune checkpoint inhibitors, which have revolutioned the treatment of metastatic melanoma and subsequently many other tumors. In 2014, nivolumab and pembrolizumab, two checkpoint inhibitors binding to PD-1, were approved for the treatment of metastatic melanoma. Since then, a plethora of new molecules have enriched the armamentarium against melanoma.

Serum CD73 is a prognostic factor in patients with metastatic melanoma and is associated with response to anti-PD-1 therapy.

Background: Inhibitors of immune checkpoint programmed cell death protein 1 (PD-1) receptor on T cells have shown remarkable clinical outcomes in metastatic melanoma. However, most patients are resistant to therapy. Production of extracellular adenosine, via CD73-mediated catabolism of AMP, contributes to suppress T-cell-mediated responses against cancer.

Impact of COVID-19 outbreak on cancer immunotherapy in Italy: a survey of young oncologists.

Background: The coronavirus disease 2019 (COVID-19) pandemic has overwhelmed the health systems worldwide. Data regarding the impact of COVID-19 on cancer patients (CPs) undergoing or candidate for immune checkpoint inhibitors (ICIs) are lacking. We depicted the practice and adaptations in the management of patients with solid tumors eligible or receiving ICIs during the COVID-19 pandemic, with a special focus on Campania region.

Immunotherapy in metastatic melanoma: a novel scenario of new toxicities and their management.

Checkpoint inhibitors can cause an imbalance in immune tolerance that may clinically manifest as immune-related adverse events (irAEs). These events may involve many organs and tissues, including the skin, gastrointestinal (GI) tract, liver, endocrine system, kidneys, central nervous system (CNS), eyes and lungs. The incidence of irAEs appears to be lower with anti-programmed death antigen-1/programmed death antigen-ligand-1 agents than with the anti-cytotoxic T-lymphocyte-associated protein-4 antibody ipilimumab.

Melanoma: Prognostic Factors and Factors Predictive of Response to Therapy.

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. Prognostic Factors: 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.

Nivolumab for the treatment of small cell lung cancer.

: Treatment of extensive-stage SCLC is still a challenge but immunotherapy with checkpoint inhibitors is showing promising results. Nivolumab alone or in combination with ipilimumab has demonstrated a benefit in terms of response and survival in patients with pre-treated extensive-stage disease and has been approved as third-line therapy after failure of chemotherapy. However, data from two phase III trials with nivolumab are negative.

The Role of BRAF-Targeted Therapy for Advanced Melanoma in the Immunotherapy Era.

Purpose Of Review: The treatment of advanced melanoma has changed dramatically in recent years with several new drugs having been approved for the treatment of melanoma since 2011. This review aims to evaluate the role of BRAF-targeted therapy for advanced melanoma in the immunotherapy era.

Recent Findings: Currently, in patients with BRAF wild-type advanced melanoma, anti-PD-1 (nivolumab or pembrolizumab) is the main treatment.

Encorafenib in combination with binimetinib for unresectable or metastatic melanoma with BRAF mutations.

Combination treatment with a BRAF inhibitor and MEK inhibitor is the standard of care for patients with advanced BRAF mutation-positive melanoma. With the currently available combinations of dabrafenib plus trametinib and vemurafenib plus cobimetinib, median progression-free survival (PFS) of over 12 months has been achieved. However, treatment resistance and disease recurrence remain a clinical challenge.