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 [...]
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 [...]
Size matters: integrating tumour volume and immune activation signatures predicts immunotherapy response.
Abstract Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, providing significant benefit to patients across various tumour types, including melanoma. However, around 40% of melanoma patients do not benefit from ICI treatment, and accurately predicting ICI response remains challenging. We now describe a novel and simple approach that integrates immune-associated transcriptome signatures and tumour volume burden to better predict ICI response in melanoma patients. RNA sequencing was performed on pre-treatment (PRE) tumour specimens derived from 32 patients with advanced melanoma treated with combination PD1 and CTLA4 inhibitors. Of these 32 patients, 11 also had early during treatment (EDT, 5-15 [...]
1094P NeoRisk: Neoadjuvant immunotherapy (NeoIT) recurrence risk assessment tool
Background NeoIT with anti-PD-1 (PD1) is now a standard of care for patients (pts) with resectable stage IIIB–D melanoma. Although pathological response is predictive of recurrence, this variable alone cannot accurately identify those pts who will recur, particularly non-responders. We sought to build a recurrence risk assessment tool based on pts demographics, disease characteristics, pathological and imaging data. Methods Pts with resectable stage IIIB–D melanoma treated with PD1-based neoIT were included. Pts demographics, disease characteristics, blood parameters, pathological and imaging data at baseline (BL) and post-treatment (post-Tx), and clinical outcomes were analysed. A penalised multivariable logistic regression model was [...]
Neoadjuvant pembrolizumab plus lenvatinib in patients with resectable stage III melanoma (NeoPele): Analysis of tumor microenvironment (TME) correlated to pathological
Abstract Background: The phase II SWOG S1801 study showed an improved event-free survival with anti-PD-1 (PD1) neoadjuvant immunotherapy (neoIT) vs adjuvant PD1. One hypothesis explaining this benefit is the presence of tumor-draining lymph nodes (tdLN; defined as the nearest node to the tumor without direct involvement) as a potential reserve of stem-like (TCF7+) T cells, crucial to a good response to IT. We sought to analyze the immune infiltrate of the tumor-involved LN (ie TME) and tdLN from patients (pts) achieving major pathological response (MPR: complete [pCR] or near-complete [near-pCR] pathological response) vs non-MPR (partial [pPR] or no [pNR] [...]
LBA41 Long-term survival with neoadjuvant therapy in melanoma: Updated pooled analysis from the International Neoadjuvant Melanoma Consortium (INMC)
Background Neoadjuvant therapy is the standard of care for resectable stage ≥IIIB melanoma. In 2021, the International Neoadjuvant Melanoma Consortium published a pooled analysis of 196 melanoma pts treated with neoadjuvant immunotherapy (ICI) or BRAF/MEK targeted therapy. Here, we provide a survival update of an expanded cohort. Methods Clinical, radiographic, histopathological, and survival data were collated for pts with resectable stage ≥IIIB melanoma who received neoadjuvant therapy in a clinical trial or routine care. Outcomes included major pathological response (MPR) rate, event-free survival (EFS; progression prior to surgery, recurrence post-surgery or death), and recurrence-free survival (RFS). Results Data was [...]
1106P NivoLag-when: International real-world study of combination immunotherapy sequences in melanoma
Background Three immune checkpoint inhibitor (ICI) regimens are standard of care in metastatic melanoma (MM): anti-PD1 combined with anti-CTLA4 (ipi/nivo), with anti-LAG3 (rela/nivo) or as monotherapy. Data describing the efficacy of sequential regimens are limited. Methods This multicenter retrospective and prospective study assessed patients (pts) who received rela/nivo followed by ipi/nivo (A); ipi/nivo followed by rela/nivo (B); or anti-PD1 followed by rela/nivo (C). Primary endpoint was objective response rate (ORR) to second treatment (Tx). Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Results With a median follow-up of 62.5 months (mo), 130 pts (A=26; B=43; C=61) [...]
1088P Molecular profiling and matched targeted therapy for patients with advanced melanoma: Results from part I of the MatchMEL study
Background While the molecular landscape of melanoma (Mel) has been defined, the clinicopathological associations of pts with BRAF/NRAS wild-type (WT) Mel and immune-checkpoint inhibitors (ICIs) treatment outcomes are less well understood. The MatchMEL study investigated the mutational profile of WT Mel and examined whether targeted treatments could be matched to specific molecular alterations with clinical efficacy. Methods In Part 1, consecutive pts with newly diagnosed advanced Mel presenting to two centres in Australia were enrolled. WT pts underwent FoundationOneCDx® (CDx) sequencing. Clinicopathologic features and ICI outcomes were examined. A molecular tumor board analysed CDx results to match targeted therapy [...]
Comparison of clinicopathological features and treatment outcomes for cutaneous melanomas of the head and neck and melanomas arising at other sites: Implications for systemic therapy.
Abstract Background: Melanoma is increasingly recognized as a heterogeneous disease, with conflicting evidence regarding whether cutaneous head and neck melanoma (CHNM) represents a distinct entity. Objective: Comparison of clinicopathological features and treatment outcomes of CHNM and cutaneous melanomas of other sites (CMOS). Methods: Patients with CHNM and CMOS diagnosed between 2000 and 2018 were included. Locoregional control, distant metastasis-free survival, melanoma-specific survival (MSS), and overall survival (OS) were described using the Kaplan-Meier method. Cox regression analyses were performed to examine associations between prognostic factors and outcomes. Additional analyses of survival from time of stage IV disease diagnosis were undertaken, stratified by receipt [...]
Exploiting temporal aspects of cancer immunotherapy
Abstract Many mechanisms underlying an effective immunotherapy-induced antitumour response are transient and critically time dependent. This is equally true for several immunological events in the tumour microenvironment induced by other cancer treatments. Immune checkpoint therapy (ICT) has proven to be very effective in the treatment of some cancers, but unfortunately, with many cancer types, most patients do not experience a benefit. To improve outcomes, a multitude of clinical trials are testing combinations of ICT with various other treatment modalities. Ideally, those combination treatments should take time-dependent immunological events into account. Recent studies have started to map the dynamic cellular [...]