Outcomes following long-term disease control with immune checkpoint inhibitors in patients with advanced melanoma
Abstract Immune checkpoint inhibitors (ICI) can achieve durable responses in patients with advanced melanoma, and results from clinical trials suggest cure may be possible for a subset of patients. Despite clinical trial data, little is known about the risk, character, and clinical outcome of late recurrences after ICI. This study aimed to explore the disease outcomes and survival in a cohort of patients with long-term responses to ICI. We retrospectively identified patients treated with ICI for advanced melanoma with long-term disease control, defined as not requiring a subsequent line of systemic therapy within 3 years of ICI commencement. We [...]
Treatment sequence with tebentafusp and immune checkpoint inhibitors in patients with metastatic uveal melanoma and metastatic GNA11/GNAQ mutant melanocytic tumors.
Abstract Background: Metastatic uveal melanoma (mUM) is rare. Immune checkpoint inhibitors (ICIs) have shown modest efficacy in mUM. Tebentafusp prolonged overall survival (OS) in a phase 3 study. We aimed to investigate the efficacy and safety of the sequence of tebentafusp and ICIs. Methods: Patients with HLA-A * 02:01 positive mUM, or metastatic GNA11/GNAQ mutant melanocytic tumors treated with tebentafusp followed by ICIs (group 1) or the inverse sequence (group 2) at any treatment line were retrospectively identified. The primary objective was OS rate at 2 years. Results: 131 patients were included; 51 in group 1 and 80 in group 2. 30 [...]
Neoadjuvant or perioperative therapy for melanoma metastasis in clinical practice: an international survey.
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Cutaneous melanoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
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Treatment sequence with tebentafusp and immune checkpoint inhibitors in patients with metastatic uveal melanoma and metastatic GNA11/GNAQ mutant melanocytic tumors.
Abstract Background: Metastatic uveal melanoma (mUM) is rare. Immune checkpoint inhibitors (ICIs) have shown modest efficacy in mUM. Tebentafusp prolonged overall survival (OS) in a phase 3 study. We aimed to investigate the efficacy and safety of the sequence of tebentafusp and ICIs. Methods: Patients with HLA-A * 02:01 positive mUM, or metastatic GNA11/GNAQ mutant melanocytic tumors treated with tebentafusp followed by ICIs (group 1) or the inverse sequence (group 2) at any treatment line were retrospectively identified. The primary objective was OS rate at 2 years. Results: 131 patients were included; 51 in group 1 and 80 in group 2. 30 [...]
X and Y Differences in Melanoma Survival Between the Sexes.
Abstract Marked differences in survival from melanoma are noted between men and women that cannot be accounted for by behavioral differences. We and others have provided evidence that this difference may be due to increased expression of immune-related genes from the second X chromosome because of failure of X inactivation. In the present review, we have examined evidence for the contrary view that survival differences are due to weaker immune responses in males. One reason for this may be the loss of Y chromosomes (LOY), particularly in older males. The genes involved may have direct roles in immune responses [...]
An updated review of immune checkpoint inhibitors in cutaneous oncology: Beyond melanoma.
Abstract Over the last decade, immune checkpoint inhibitors (ICIs) have been established as an integral component of the contemporary anticancer armamentarium. In dermatology, ICIs are most established as treatment of advanced melanoma. However, emerging evidence has demonstrated that their utility in cutaneous oncology extends to a variety of other non-melanoma malignancies. This review provides an update of the evidence from clinical trials, real world analyses, and translational research over the last three years in cutaneous malignancies beyond melanoma. Special focus is presented on areas warranting further evaluation - including populations underrepresented in or excluded from clinical trials; new and [...]
ASO Author Reflections: Is Sentinel Node Biopsy Still of Value for Patients with High-Risk Primary Melanomas Eligible for Adjuvant Immunotherapy?
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Uncovering the molecular mechanisms of amelanotic/hypopigmented primary cutaneous melanoma
Abstract Background: Approximately 2-20% of cutaneous melanomas (CMs) are diagnosed as amelanotic/hypopigmented melanoma (AHM) and represent a challenge for early diagnosis. Objectives: To investigate loss-of-function mutations in key pigmentation genes in matched germline and AHM, as well as pigmented melanoma (PM), tumour DNA samples. Methods: Analysis of clinical and histopathological characteristics - together with whole-exome sequencing data of 34 fresh frozen primary CMs, graded according to the amount of pigmentation present - was performed. Together with germline and somatic variant analysis, 30 samples had previously been analysed for copy number aberration (CNA) changes. This study focused on germline and somatic variants in [...]
Impact of alternative diagnostic labels for melanoma in situ on management choices and psychological outcomes: protocol for an online randomised study.
Abstract Introduction: A diagnosis of melanoma in situ presents negligible risk to a person's lifespan or physical well-being, but existing terminology makes it difficult for patients to distinguish these from higher risk invasive melanomas. This study aims to explore whether using an alternative label for melanoma in situ may influence patients' management choices and anxiety levels. Methods and analysis: This study is a between-subjects randomised online experiment, using hypothetical scenarios. Following consent, eligible participants will be randomised 1:1:1 to three labels: 'melanoma in situ' (control), 'low-risk melanocytic neoplasm' (intervention 1) and 'low-risk melanocytic neoplasm, in situ' (intervention 2). The required sample [...]