Sapna Patel, BA, MD

Panelists discuss the complexities of selecting among second- and third-line therapies such as tumor-infiltrating lymphocyte (TIL), T-cell receptor T-cell (TCR-T), and oncolytic viruses, emphasizing that treatment choice will depend on emerging data, patient factors, practical considerations, and quality of life, with ongoing trials and clinical experience guiding optimal sequencing.

Panelists discuss the promising systemic responses of RP1, an oncolytic virus therapy for melanoma, emphasizing its expanded applicability through visceral tumor injection and the need for further data to optimize dosing strategies and confirm durability compared with other treatments.

Panelists discuss the emerging role of PRAME-targeted T-cell receptor T-cell (TCR-T) therapies in melanoma, highlighting a novel clinical trial comparing TCR-T and tumor-infiltrating lymphocyte (TIL) treatments that focuses on HLA-A*02:01-positive patients and aims to provide patient-friendly, outpatient-compatible options with faster manufacturing timelines.

Panelists discuss the distinctions among tumor-infiltrating lymphocyte (TIL), chimeric antigen receptor (CAR) T-cell, and T-cell receptor T-cell (TCR-T) therapies in melanoma, emphasizing TIL therapy’s polyclonal nature and regulatory challenges while highlighting the promise of engineered TCR-T cells and the need to balance scientific validation with clinical feasibility to maintain access to innovative treatments.

Panelists discuss the need for early, coordinated, and multidisciplinary care to ensure timely access to tumor-infiltrating lymphocyte (TIL) therapy, highlighting the importance of integrated communication, patient-centered planning, and shared decision-making—especially for older patients navigating complex treatment choices.

Panelists discuss the critical importance of early referral and coordinated communication between community oncologists and treatment centers to ensure timely evaluation and access to tumor-infiltrating lymphocyte (TIL) therapy, emphasizing outreach efforts to raise awareness and streamline patient pathways.

Panelists discuss 5-year data from a trial of lifileucel, a tumor-infiltrating lymphocyte (TIL) therapy, highlighting its promising long-term survival benefits and growing role in standard care for advanced cancers, especially in patients unresponsive to prior treatments.

Panelists discuss the challenges of managing brain metastases in patients with melanoma after frontline therapy, highlighting the roles of localized treatments, targeted therapies for actionable mutations, limited options for symptomatic cases, and the urgent need for improved strategies for central nervous system (CNS) and leptomeningeal disease (LMD) management.

Panelists discuss expanding treatment options beyond frontline therapy for metastatic melanoma, emphasizing the use of targeted therapies, combination immunotherapies, and emerging modalities such as oncolytic virus and adoptive cell therapy while highlighting the balance between efficacy, toxicity, patient-centered outcomes, and practical challenges in clinical decision-making.

Panelists discuss the evolving role of circulating tumor DNA (ctDNA) in metastatic melanoma management, recognizing its potential as a minimal residual disease (MRD) marker and monitoring tool while emphasizing current limitations, investigational status, and the need for further research to define its clinical utility.

Panelists discuss emerging strategies to reduce toxicity in dual immune checkpoint blockade for metastatic melanoma, focusing on promising early data with anti–IL-6 agents such as sarilumab. They acknowledge challenges around scalability, cost, and validation in broader populations and emphasize the importance of ongoing research and clinical trials to optimize tolerability without compromising efficacy.

Panelists discuss treatment sequencing for BRAF-mutated metastatic melanoma, highlighting evidence from the DREAMseq trial that supports starting with immunotherapy for better long-term survival while acknowledging clinical scenarios where rapid-response targeted therapy may be appropriate and emphasizing the need for flexibility based on patient condition and emerging data.

Panelists discuss frontline treatment preferences for metastatic melanoma, emphasizing the durability of combination immunotherapies like nivolumab plus ipilimumab, the emerging role of nivolumab plus relatlimab, and the importance of tailoring therapy based on disease characteristics, toxicity profiles, and individual patient factors.

Panelists discuss modern approaches to metastatic melanoma, focusing on recent advances in immunotherapy and cell therapies, individualized frontline treatment strategies, and evolving clinical data to guide clinicians in optimizing patient outcomes.

Sapna Patel, MD, discusses the potential for adjuvant immunotherapy in patients with high-risk cutaneous squamous cell carcinoma.

The panel concludes their discussion with a call for continued research and collaboration, emphasizing the need for more understanding of targeted therapies, monitoring tools like ctDNA, and ongoing development in the field of BRAF mutant melanoma treatment.

Doctors discuss the effectiveness of different treatment combinations for patients with BRAF-mutated metastatic melanoma and brain metastases, highlighting that consideration of patient preferences is essential in making treatment decisions.

Experts discuss treatment of patients with BRAF-mutated melanoma and symptomatic brain metastases, detailing radiation therapy, corticosteroid use, and the choice between BRAF/MEK inhibitor therapy and immunotherapy.

For patients with BRAF-mutated melanoma with asymptomatic brain metastases, immunotherapy, particularly the combination of ipilimumab and nivolumab, is the preferred treatment option due to its effectiveness and durability, as supported by the seven-year follow-up data from the CHECKMATE 204 trial.

Panelists discuss the potential benefits of rechallenging patients with BRAF-mutated metastatic melanoma with BRAF/MEK inhibitors after a break from treatment, especially for those who initially responded well, and emphasizing the success of this approach in some cases, while highlighting the importance of monitoring and utilizing ctDNA tracking for more informed decision-making.

The 7-year follow-up data for encorafenib/binimetinib showing that around 21% of patients remained progression-free supports BRAF/MEK inhibition as a later treatment option after immunotherapy failure, but doctors are reluctant to stop BRAF/MEK inhibitors given lack of data, even in those patients doing well long-term on the medications with minimal toxicity.

The panel explains which BRAF/MEK inhibitor combination therapy they each tend to turn to when treating a patient with BRAF-mutated metastatic melanoma.

Key opinion leaders explain that clinicians should warn patients with BRAF-mutated metastatic melanoma starting BRAF/MEK inhibitor therapy about short-term toxicities like fever, chills, and rash that can differ greatly from immunotherapy toxicities.

Experts discuss a preference for ipilimumab/nivolumab as the frontline immunotherapy for patients with BRAF-mutant metastatic melanoma given its proven long-term efficacy but acknowledge nivolumab/relatlimab as an option with less toxicity, especially adrenal insufficiency.

Beyond symptoms, doctors consider the psychosocial factors impacting treatment access and adherence, like insurance coverage, cost, family support, and preexisting conditions, when deciding between immunotherapy and targeted therapy for patients with BRAF-mutated metastatic melanoma.

For patients with BRAF-mutant metastatic melanoma, doctors assess symptoms and disease status to determine if they should start treatment with combination immunotherapy, or 8-12 weeks of BRAF/MEK targeted therapy before switching to immunotherapy, which offers the possibility of durable responses or cure.

The panelists emphasize the importance of obtaining tissue for BRAF-mutation testing and dedicated tissue tracking in patients with metastatic melanoma, with immunohistochemistry followed by confirmatory next-generation sequencing, and discuss the promise of liquid biopsies like ctDNA as a future biomarker tracking modality.

When a patient with metastatic melanoma patient tests negative for the BRAF V600E mutation, doctors recommend sending the sample for next-generation sequencing testing which can take 2-3 weeks, during which time they may start immunotherapy if the patient has aggressive disease, but ideally should wait for results to guide treatment.

Expert panelists stress the importance of biomarker testing for BRAF mutations to guide treatment options when a patient is diagnosed with metastatic melanoma.

Sapna Patel, BA, MD, discusses the rationale for evaluating the use of pembrolizumab before and after surgery for patients with advanced melanoma.