Patient and Staff Experiences of Embedding Electronic Patient Reported Outcome Measures for Distress Screening and Quality of Life Assessment, Into Routine Melanoma Care: A Mixed-Methods Study.
Abstract Objective: Patient reported outcome measures (PROMs) are commonly collected in melanoma research. However, they are not used to guide immediate clinical care in Australia. This study explored the views and experiences of patients with Stage III melanoma and clinic staff during implementation of an electronic Patient-Reported Outcome Measures in melanoma (ePROMs-MEL) pilot to assess distress and quality of life. Methods: A prospective mixed-methods study in specialist melanoma clinics in Sydney, Australia between May 2021 and February 2023. Forty-two post-ePROMs implementation surveys and 17 semi-structured interviews were undertaken among patients and staff (including oncologists, melanoma nurses and clinic managers). Survey responses [...]
Impact of personalized response-directed surgery and adjuvant therapy on survival after neoadjuvant immunotherapy in stage III melanoma: Comparison of 3-year data from PRADO and OpACIN-neo.
Abstract Background: Pathologic response following neoadjuvant immune checkpoint blockade (ICB) in stage III melanoma serves as a surrogate marker for long-term outcomes. This may support more personalized, response-directed treatment strategies. Methods: The OpACIN-neo and PRADO trials were phase 2 studies evaluating neoadjuvant treatment with ipilimumab and nivolumab in stage III melanoma. In OpACIN-neo, all patients underwent therapeutic lymph node dissection (TLND) without subsequent adjuvant therapy. In contrast, PRADO explored a response- directed strategy, where patients achieving a major pathologic response (MPR) omitted TLND and adjuvant therapy, while those without a pathologic response (pNR) received TLND and adjuvant therapy. Here, we provide [...]
Relapse-free survival with adjuvant dabrafenib/trametinib therapy after relapse on a prior adjuvant CPI in BRAF V600-mutated stage III/IV melanoma.
Abstract Background: In BRAF-mutated high-risk melanoma, targeted therapy (BRAF/MEK inhibitors) and checkpoint inhibitor (CPI) immunotherapy have durable benefits as first-line (1L) adjuvant therapy. Based on differing action mechanisms of BRAF/MEK inhibitors and CPI immunotherapies, there is interest in evaluating the activity of 2L adjuvant targeted therapy in decreasing the risk of subsequent recurrence after repeat resection following relapse on/after 1L adjuvant CPI. Patients and methods: This was a retrospective review of BRAF V600-mutated resected stage III/IV melanoma patients in the United States, Australia, and The Netherlands who received 1L adjuvant CPI immunotherapy, relapsed locoregionally/distantly, were again resected to no evidence of [...]
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 [...]