{
  "abstract": "Background Immune checkpoint inhibitors (ICIs) have revolutionized melanoma treatment, with programmed cell death protein 1 (PD-1) inhibitors—alone or in combination with cytotoxic T-lymphocyte–associated protein 4 or lymphocyte-activation gene 3 inhibitors—demonstrating significant efficacy. However, there is a critical lack of robust data to determine the optimal sequencing of these therapies for individual patients. In particular, the role of relatlimab+nivolumab (rela/nivo) within treatment sequences remains poorly defined. Choosing the right sequence is strategic, as an inappropriate order may compromise the effectiveness of subsequent treatments and limit long-term benefits.Methods This multicenter retrospective and prospective study evaluated 190 patients across three treatment arms: rela/nivo followed by ipilimumab+nivolumab (ipi/nivo) (arm A, N=40), ipi/nivo followed by rela/nivo (arm B, N=71), and anti-PD-1 followed by rela/nivo (arm C, N=79). The study assessed the impact of treatment sequencing on outcomes including response rate, progression-free survival, and overall survival (OS).Results The overall response rate to second treatment was highest in arm C (30.4%), followed by arm B (28.1%) and arm A (17.5%). Patients with secondary resistance to first-treatment ICIs had better responses to second-treatment ICIs than those with primary resistance, particularly in arm B (p=0026). Median OS from date of first ICI treatment was significantly longer in arms B (40.9 months) and C (42.5 months) compared with arm A (16.3 months).Conclusions Our findings indicate that rela/nivo may remain active following anti-PD-1 or ipi/nivo therapy. Additionally, our results suggest that sequencing ipi/nivo before rela/nivo may yield better outcomes than starting with rela/nivo. Patients who respond to the first combination regimen appear to derive greater benefit from the second. Further efforts are needed to optimize sequencing strategies in advanced melanoma, and future studies should consider the impact of prior treatment outcomes.",
  "authors": [
    {
      "affiliations": [
        "Département de médecine oncologique, Gustave Roussy, Villejuif, France"
      ],
      "name": "Mora Guardamagna"
    },
    {
      "affiliations": [
        "Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA"
      ],
      "name": "Sarah E Lochrin"
    },
    {
      "affiliations": [
        "Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "James William Smithy"
    },
    {
      "affiliations": [
        "Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Michael Postow"
    },
    {
      "affiliations": [
        "Dermatology and Skin Cancer, Aix-Marseille University, Marseille, France",
        "INSERM U1068, Marseille, France"
      ],
      "name": "Caroline Gaudy-Marqueste"
    },
    {
      "affiliations": [
        "Dermatology and Skin Cancer, Aix-Marseille University, Marseille, France",
        "INSERM U1068, Marseille, France"
      ],
      "name": "Nausicaa Malissen"
    },
    {
      "affiliations": [
        "Dermatology and Skin Cancer, Aix-Marseille University, Marseille, France",
        "INSERM U1068, Marseille, France"
      ],
      "name": "Sandrine Monestier"
    },
    {
      "affiliations": [
        "Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA"
      ],
      "name": "Ryan J Sullivan"
    },
    {
      "affiliations": [
        "Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA"
      ],
      "name": "Juliane A Czapla"
    },
    {
      "affiliations": [
        "Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA"
      ],
      "name": "Aleigha R Lawless"
    },
    {
      "affiliations": [
        "Melanoma Institute Australia, North Sydney, New South Wales, Australia",
        "The University of Sydney, Sydney, New South Wales, Australia"
      ],
      "name": "Ines Pires da Silva"
    },
    {
      "affiliations": [
        "Melanoma Institute Australia, North Sydney, New South Wales, Australia",
        "The University of Sydney, Sydney, New South Wales, Australia"
      ],
      "name": "Georgina V Long"
    },
    {
      "affiliations": [
        "Melanoma Institute Australia, North Sydney, New South Wales, Australia",
        "The University of Sydney, Sydney, New South Wales, Australia"
      ],
      "name": "Alexander Maxwell Menzies"
    },
    {
      "affiliations": [
        "Dermatology, University Hospital Zurich, Zürich, Switzerland"
      ],
      "name": "Florentia Dimitriou"
    },
    {
      "affiliations": [
        "Dermatology, University Hospital Zurich, Zürich, Switzerland"
      ],
      "name": "Reinhard Dummer"
    },
    {
      "affiliations": [
        "Dermatology, Hospices Civils de Lyon, Lyon, France"
      ],
      "name": "Caroline Marchi"
    },
    {
      "affiliations": [
        "Dermatology, Hospices Civils de Lyon, Lyon, France"
      ],
      "name": "Amandine Chaurand"
    },
    {
      "affiliations": [
        "Dermatology, Hospices Civils de Lyon, Lyon, France"
      ],
      "name": "Stéphane Dalle"
    },
    {
      "affiliations": [
        "Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy"
      ],
      "name": "Paolo A Ascierto"
    },
    {
      "affiliations": [
        "Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy"
      ],
      "name": "Miriam Paone"
    },
    {
      "affiliations": [
        "Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy"
      ],
      "name": "Bianca Arianna Facchini"
    },
    {
      "affiliations": [
        "Oncology, Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA",
        "Johns Hopkins University The Bloomberg~Kimmel Institute for Cancer Immunotherapy, Baltimore, Maryland, USA"
      ],
      "name": "Govind Warrier"
    },
    {
      "affiliations": [
        "Oncology, Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA",
        "Johns Hopkins University The Bloomberg~Kimmel Institute for Cancer Immunotherapy, Baltimore, Maryland, USA"
      ],
      "name": "Evan J Lipson"
    },
    {
      "affiliations": [
        "Dermatology, Uniklinikum Erlangen, Deutsches Zentrum Immuntherapie (DZI), Comprehensive Cancer Center Erlangen, Erlangen, Germany",
        "Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Germany"
      ],
      "name": "Michael Erdmann"
    },
    {
      "affiliations": [
        "Dermatology, Uniklinikum Erlangen, Deutsches Zentrum Immuntherapie (DZI), Comprehensive Cancer Center Erlangen, Erlangen, Germany",
        "Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Germany"
      ],
      "name": "Carola Berking"
    },
    {
      "affiliations": [
        "Département de biostatistiques et d'épidémiologie, Gustave Roussy, Villejuif, France",
        "Oncostat, INSERM U1018, Villejuif, France"
      ],
      "name": "Baptiste Archambaud"
    },
    {
      "affiliations": [
        "Département de médecine oncologique, Gustave Roussy, Villejuif, France"
      ],
      "name": "Severine Roy"
    },
    {
      "affiliations": [
        "Département de médecine oncologique, Gustave Roussy, Villejuif, France"
      ],
      "name": "Emilie Routier"
    },
    {
      "affiliations": [
        "Département de médecine oncologique, Gustave Roussy, Villejuif, France"
      ],
      "name": "Celine Boutros"
    },
    {
      "affiliations": [
        "Département de médecine oncologique, Gustave Roussy, Villejuif, France"
      ],
      "name": "Philippe Jamme"
    },
    {
      "affiliations": [
        "Département de médecine oncologique, Gustave Roussy, Villejuif, France"
      ],
      "name": "Djaouida Belkadi-Sadou"
    },
    {
      "affiliations": [
        "Département de biostatistiques et d'épidémiologie, Gustave Roussy, Villejuif, France",
        "Oncostat, INSERM U1018, Villejuif, France"
      ],
      "name": "Noemie Simon-Tillaux"
    },
    {
      "affiliations": [
        "Département de médecine oncologique, Gustave Roussy, Villejuif, France",
        "Université Paris-Saclay, Gustave Roussy, Inserm Prédicteurs moléculaires et nouvelles cibles en oncologie, Villejuif, France"
      ],
      "name": "Caroline Robert"
    }
  ],
  "title": "International real-world study of combination immunotherapy sequences in metastatic melanoma",
  "uid": "c03e7f75-0af2-5b56-b2d1-9bb5045aaaa3"
}