Progress in Immune Checkpoint Inhibitor for Melanoma Therapy.

Melanoma has seen the most remarkable therapeutic improvements among all cancers in the past decade, primarily due to the development of immune checkpoint inhibitors (ICI). Initially developed in the patients with advanced disease, ICI are now used in adjuvant and neoadjuvant settings. More recently, the development of LAG-3 blocking antibody and the combination of ICI with a personalized RNA-based vaccine have continued to lead the immunotherapeutic field.

Cured or Not? Long-term Outcomes of Immunotherapy Responders. Focus on Melanoma.

Purpose Of Review: Immune checkpoint inhibitors (ICIs) demonstrated robust antitumor activity and tolerable safety in advanced melanoma. Data on long-term outcome of patients who benefited from this therapy and who are still free of progression despite ICI discontinuation is now available. We review here the characteristics of long-term ICI responders and address the critical question of cure.

Outcomes of patients with cancer and sarcoid-like granulomatosis associated with immune checkpoint inhibitors: A case-control study.

Purpose: Sarcoid-like granulomatosis (SLG) reaction caused by immunotherapy remains poorly understood. This study aims to investigate the outcome of patients with cancer and SLG associated with immunotherapy.

Patients And Methods: Between April 2016 and June 2020, 434 patients with immunological adverse events were screened from the ImmunoTOX assessment board of Gustave Roussy, an academic cancer centre in France.

Immune Checkpoint Inhibitor Therapy Aggravates T Cell-Driven Plaque Inflammation in Atherosclerosis.

Background: Immunotherapy has revolutionized cancer treatment. However, immune checkpoint inhibitors (ICIs) that target PD-1 (programmed cell death protein-1) and/or CTLA-4 (cytotoxic T lymphocyte-associated antigen-4) are commonly associated with acute immune-related adverse events. Accumulating evidence also suggests that ICIs aggravate existing inflammatory diseases.

Long-term safety of pembrolizumab monotherapy and relationship with clinical outcome: A landmark analysis in patients with advanced melanoma.

Objective: Long-term safety of pembrolizumab in melanoma was analyzed in KEYNOTE-001, KEYNOTE-002, and KEYNOTE-006.

Patients And Methods: Analysis involved patients who received ≥1 pembrolizumab dose. Lead-time bias was addressed via landmark analyses in patients who were progression-free before day 147.

Dose escalation phase 1 study of radiotherapy in combination with anti-cytotoxic-T-lymphocyte-associated antigen 4 monoclonal antibody ipilimumab in patients with metastatic melanoma.

Background: A synergy between radiotherapy and anti-cytotoxic-T-lymphocyte-associated antigen 4 (anti-CTLA-4) monoclonal antibody has been demonstrated preclinically. The Mel-Ipi-Rx phase 1 study aimed to determine the maximum tolerated dose (MTD) and safety profile of radiotherapy combined with ipilimumab in patients with metastatic melanoma.

Patients And Methods: A 3+3 dose escalation design was used with 9, 15, 18 and 24 Gy dose of radiotherapy at week 4 combined with 10 mg/kg ipilimumab every 3 weeks for four doses.

New Era in the Management of Melanoma Brain Metastases.

The remarkable advances in the systemic therapy of metastatic melanoma have now extended the 1-year overall survival rate from 25% to nearing 85%. Systemic treatment in the form of BRAF-targeted therapy and immunotherapy is slowly but surely proving its efficacy in the treatment of metatstatic brain metastases (MBM). Single-agent BRAF inhibitors provide an intracranial response rate of 25% to 40%, whereas the combination of BRAFi/MEKi leads to responses in up to 58%.

Transcriptional response to hypoxic stress in melanoma and prognostic potential of GBE1 and BNIP3.

Gradients of hypoxia occur in most solid tumors and cells found in hypoxic regions are associated with the most aggressive and therapy-resistant fractions of the tumor. Despite the ubiquity and importance of hypoxia responses, little is known about the variation in the global transcriptional response to hypoxia in melanoma. Using microarray technology, whole genome gene expression profiling was first performed on established melanoma cell lines.

Renal effects of immune checkpoint inhibitors.

Recent advances in immune checkpoint inhibitor (ICPI) development have led to major improvements in oncology patient outcomes. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) are two essential immune checkpoint receptors. Ipilimumab and tremelimumab (anti-CTLA-4-blocking antibodies) and pembrolizumab and nivolumab (antibodies targeting PD-1 receptors) have already been approved by US Food and Drug Administration in several malignancies.

A Novel Spectroscopically Determined Pharmacodynamic Biomarker for Skin Toxicity in Cancer Patients Treated with Targeted Agents.

Raman spectroscopy is a noninvasive and label-free optical technique that provides detailed information about the molecular composition of a sample. In this study, we evaluated the potential of Raman spectroscopy to predict skin toxicity due to tyrosine kinase inhibitors treatment. We acquired Raman spectra of skin of patients undergoing treatment with MEK, EGFR, or BRAF inhibitors, which are known to induce severe skin toxicity; for this pilot study, three patients were included for each inhibitor.

Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination.

Inhibition of immune checkpoints using anti-programmed cell death-1 (PD-1) or anti cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibodies has revolutionized the management of patients with advanced-stage melanoma and is among the most promising treatment approaches for many other cancers. Use of CTLA-4 and PD-1 inhibitors, either as single agents, or in combination, has been approved by the US FDA for the treatment of metastatic melanoma. Treatment with these novel immunotherapies results in a unique and distinct spectrum of adverse events, which are mostly related to activation of the immune system and are, therefore, an unwanted consequence of their mechanisms of action.

Association of Vitiligo With Tumor Response in Patients With Metastatic Melanoma Treated With Pembrolizumab.

Importance: Vitiligo is an autoimmune skin disorder that reacts against melanocytes. The association of vitiligo with tumor response in patients with melanoma who undergo immunotherapy has been reported but is still controversial.

Objective: To prospectively evaluate the appearance of vitiligo in patients receiving pembrolizumab, a monoclonal antibody directed against the programmed death cell receptor.

Effect of time to sentinel-node biopsy on the prognosis of cutaneous melanoma.

Introduction: In patients with primary cutaneous melanoma, there is generally a delay between excisional biopsy of the primary tumour and sentinel-node biopsy. The objective of this study is to analyse the prognostic implications of this delay.

Patients And Method: This was an observational, retrospective, cohort study in four tertiary referral hospitals.

Sequential therapy with gemcitabine and Carboplatin followed by Paclitaxel as first line treatment for advanced urothelial cancer.

Objective: Gemcitabine and platinum-based compounds represent the new standard combination therapy for bladder cancer. In this study, we evaluate the efficacy and safety of gemcitabine and carboplatin followed sequentially by paclitaxel in 27 patients with advanced transitional cell carcinoma.

Methods: This phase II multicentre study was based on the doublet gemcitabine 800 mg/m2 and carboplatin area under the concentration-time curve 2 on days 1 and 8 every 21 days for 4 cycles, followed sequentially by paclitaxel 60 mg/m(2)/w for 12 consecutive weeks.

Experience with palliative care in patients with advanced cancer at a tertiary care hospital in a developing country.

The importance of palliative care in patients with advanced cancer is established. Reports on the experience with palliative care in the Middle East region are limited. A prospective study was performed to characterize the palliative care experience at a tertiary care center in Lebanon and to identify the profile of patients requiring palliative care.