7760 Identifying Conventional and Novel Biomarkers to Predict Checkpoint Inhibitor Associated Autoimmune Diabetes
Abstract Introduction: Checkpoint inhibitor associated autoimmune diabetes (CIADM) is a rare but highly morbid complication of immune checkpoint inhibitor (ICI) therapy. As indications for ICIs expand, the ability to predict CIADM has huge potential value and has yet to extensively explored. Aims: To identify potential biomarkers for prediction of CIADM in patients commencing ICI therapy. Methods: 14 patients with metastatic melanoma treated with ICI who subsequently developed CIADM were identified. 28 matched controls were identified (matched for ICI type, gender, cancer response and other immune related adverse events). Pre-treatment, on ICI and post CIADM serum and PBMCs were analysed. [...]
Nature and management of melanoma recurrences following adjuvant anti-PD-1 based therapy
Abstract Introduction: Approximately 50 % of resected stage II-IV melanoma patients develop recurrent disease by 5 years despite adjuvant anti-PD-1 therapy. Data to define best management of recurrences is lacking. Methods: This was a multicentre, international, retrospective cohort study. Patients with resected stage II-IV melanoma who commenced adjuvant anti-PD-1-based therapy before January 2022 and later recurred were identified. Data on demographics, disease characteristics, recurrence patterns, management and outcomes were collected. Results: 711 patients from 17 sites were included. Median age was 60 [range 16-92], 64 % were male, 2 % stage II, 91 % were stage III, 7 % stage IV. Median [...]
1090P High concurrent interferon gamma signature expression in the primary tumor and lymph node metastasis is associated with superior outcome upon neoadjuvant ipilimumab + nivolumab in stage III melanoma
Background The interferon gamma gene signature (IFNg) has been shown to be predictive and prognostic in patients (pts) with macroscopic stage III or IV melanoma. In macroscopic stage III melanoma, IFNg from lymph node biopsies (LN-IFNg) might be used in the future for neoadjuvant treatment decisions (combination vs monotherapy). To address the question of whether the IFNg can be analyzed using primary tumor material (P-IFNg) instead of LN-IFNg or, in the case of incongruencies, has a higher predictive value when combined with LN-IFNg, we analyzed the IFNg signature in paired samples (P and LN) from stage III melanoma pts. [...]
1082O KEYMAKER-U02 substudy 02C: Neoadjuvant pembrolizumab (pembro) and investigational agents followed by adjuvant pembro for stage IIIB-D melanoma
Background Substudy 02C of the phase 1/2 KEYMAKER-U02 trial (NCT04303169) is evaluating neoadjuvant pembro with or without investigational agents followed by adjuvant pembro for stage IIIB-D melanoma. We present initial results from arm 4 (pembro + MK-4830 [anti-ILT4]) and arm 5 (favezelimab [anti-LAG-3] coformulated with pembro [fave/pembro]) and updated results from arm 1 (pembro + vibostolimab [vibo; anti-TIGIT]), arm 2 (pembro + gebasaxturev [geba; coxsackievirus A21]), and arm 3 (pembro alone). Methods Adults with resectable stage IIIB-D melanoma were randomly assigned to open arms. Patients (pts) received 2 doses of pembro 200 mg Q3W + vibo 200 mg Q3W [...]
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 [...]
72MO Concurrent BRAF targeted therapy (TT) with dabrafenib and trametinib and anti-PD-1 agent pembrolizumab (PD1) increased B cell signalling and inflammatory pathways more effectively than when given sequentially or with anti-PD-1 alone
Background Long duration TT prior to immunotherapy(IO) is inferior to IO upfront for patients with advanced BRAFV600 mutant melanoma while short duration TT continues to be investigated. The previously presented results of the neoadjuvant(NA) NeoTrio clinical trial (NCT02858921) demonstrated concurrent TT with PD1 yielded the highest pathologic response rates compared to 1 week of TT followed by PD1 or PD1 alone, although durability of pathological response was better with PD1 alone. We sought to characterise longitudinal changes to the tumour microenvironment induced by treatment. Methods In NeoTrio, 60 patients with BRAFV600 mutant stage IIIB/C/D melanoma were randomised to 6 weeks of [...]
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 [...]