Long-term Outcomes among Patients Who Respond within the First Year to Nivolumab plus Ipilimumab or Nivolumab Monotherapy: A Pooled Analysis in 935 Patients.
Abstract Purpose: To investigate the predictive value of RECIST response within 3, 6, or 12 months on long-term survival, and explore differences between nivolumab+ipilimumab and nivolumab monotherapy, we analyzed pooled 5-year data of 935 responder and non-responder patients at various time points after treatment initiation in CheckMate 069, 066, and 067 studies. Patients and methods: Treatment-naive advanced melanoma patients received nivolumab+ipilimumab or nivolumab monotherapy. To decrease immortal time bias, 3-, 6-, or 12-month overall survival (OS) and progression-free survival (PFS) landmark analyses were performed. Association between characteristics and response was evaluated by univariate and multivariate analyses. Results: Response rates at any time [...]
Cutaneous melanoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.
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A comparison of isolated limb infusion/perfusion, immune checkpoint inhibitors, and intralesional therapy as first-line treatment for patients with melanoma in-transit metastases
Abstract Background: Isolated limb infusion and perfusion (ILI/ILP) has been a mainstay treatment for unresectable melanoma in-transit metastases (ITM), but increased use of immune checkpoint inhibitors (ICI) and intralesional therapy (talimogene laherparepvec [TVEC]) introduced several different management options. This study compares first-line ILI/ILP, ICI, and TVEC. Methods: Retrospective review from 12 international institutions included patients treated from 1990 to 2022 with first-line ILI/ILP, ICI, or TVEC for unresectable melanoma ITM. Results: A total of 551 patients were treated, with ILI/ILP (n = 356), ICI (n = 125), and TVEC (n = 70) with median follow-up of 5.5 years. Tumor burden was highest [...]
A comparison of isolated limb infusion/perfusion, immune checkpoint inhibitors, and intralesional therapy as first-line treatment for patients with melanoma in-transit metastases
Abstract Background: Isolated limb infusion and perfusion (ILI/ILP) has been a mainstay treatment for unresectable melanoma in-transit metastases (ITM), but increased use of immune checkpoint inhibitors (ICI) and intralesional therapy (talimogene laherparepvec [TVEC]) introduced several different management options. This study compares first-line ILI/ILP, ICI, and TVEC. Methods: Retrospective review from 12 international institutions included patients treated from 1990 to 2022 with first-line ILI/ILP, ICI, or TVEC for unresectable melanoma ITM. Results: A total of 551 patients were treated, with ILI/ILP (n = 356), ICI (n = 125), and TVEC (n = 70) with median follow-up of 5.5 years. Tumor burden was highest [...]
Pooled Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone in Patients With Advanced Melanoma.
Abstract Purpose: Nivolumab (NIVO) + ipilimumab (IPI) combination and NIVO monotherapy have demonstrated durable clinical benefit in patients with unresectable/metastatic melanoma. This analysis describes long-term overall survival (OS) with the combination or monotherapy pooled across all major company-sponsored trials, as well as clinical factors associated with survival, in patients with immune checkpoint inhibitor (ICI) treatment-naïve unresectable/metastatic melanoma. Methods: Data were pooled from six CheckMate studies in ICI treatment-naïve patients receiving NIVO + IPI (NIVO 1 mg/kg + IPI 3 mg/kg or NIVO 3 mg/kg + IPI 1 mg/kg) or NIVO monotherapy (3 mg/kg). OS was assessed for each treatment, as well [...]
Seven-year analysis of adjuvant pembrolizumab versus placebo in stage III melanoma in the EORTC1325 / KEYNOTE-054 trial.
Abstract In the previously reported primary analyses of this phase 3 trial, 12 months of adjuvant pembrolizumab resulted in significantly longer recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) than placebo in patients with resected high risk stage III melanoma. Stability of these benefits when the median follow-up was 3.5 and 5 years was published. Here we report results with a longer follow-up. Methods: We randomized 1019 patients to receive pembrolizumab 200 mg or placebo, intravenously every 3 weeks for a total of 18 doses. RFS in the overall population and in the subgroup of patients with melanoma positive for [...]
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 [...]
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. [...]
The Prognostic Significance of Tumoral Melanosis
Abstract Background: Tumoral melanosis (TM) is a histological term to describe a nodular aggregation of macrophages containing melanin pigment (melanophages) that is devoid of viable melanocytes. It is most often identified in skin, where it may be appreciated clinically as a pigmented lesion; however, it can also be found in other organs such as lymph nodes. The presence of TM is usually thought to signify the presence of a regressed melanoma or other pigmented tumor. Until recently, it was a relatively uncommon finding; however, with the use of effective systemic therapies against melanoma, its occurrence in histological specimens is more [...]
A brave new framework for glioma drug development.
Abstract Patients with brain tumours are motivated to participate in clinical trials involving repeat tissue sampling. Normalising the use of neoadjuvant and staged surgical trials necessitates collaboration among patients, regulatory agencies, and researchers. Initial and repetitive tissue sampling plays a crucial role in enhancing our understanding of resistance mechanisms and vulnerabilities in brain tumour therapy. Standardising biopsy techniques and ensuring technical uniformity across institutions are vital for effective interinstitutional collaboration. Although liquid biopsy technologies hold promise, they are not yet ready to replace tissue analysis. Clear communication about the risks and benefits of biopsies is essential, particularly regarding potential [...]