International real-world study of combination immunotherapy sequences in metastatic melanoma.

Guardamagna M, Lochrin SE, Smithy JW, Postow M, Gaudy-Marqueste C, Malissen N, Monestier S, Sullivan RJ, Czapla JA, Lawless AR, Pires da Silva I, Long GV, Menzies AM, Dimitriou F, Dummer R, Marchi C, Chaurand A, Dalle S, Ascierto PA, Paone M, Facchini BA, Warrier G, Lipson EJ, Erdmann M, Berking C, Archambaud B, Roy S, Routier E, Boutros C, Jamme P, Belkadi-Sadou D, Simon-Tillaux N, Robert C (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Journal for ImmunoTherapy of Cancer BioMed Central

Book Volume: 13

Journal Issue: 11

DOI: 10.1136/jitc-2025-012225

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 with CRIS profile

Michael Erdmann Department of Dermatology Carola Berking Lehrstuhl für Haut- und Geschlechtskrankheiten

Involved external institutions

Institut Gustave-Roussy FR France (FR) Memorial Sloan Kettering Cancer Center US United States (USA) (US) Aix-Marseille University / Aix-Marseille Université FR France (FR) Massachusetts General Hospital US United States (USA) (US) Hospices Civils de Lyon (CHU) FR France (FR) Melanoma Institute Australia AU Australia (AU) Universitätsspital Zürich (USZ) CH Switzerland (CH) Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" IT Italy (IT) Sidney Kimmel Comprehensive Cancer Center (SKCCC) US United States (USA) (US)

How to cite

APA:

Guardamagna, M., Lochrin, S.E., Smithy, J.W., Postow, M., Gaudy-Marqueste, C., Malissen, N.,... Robert, C. (2025). International real-world study of combination immunotherapy sequences in metastatic melanoma. Journal for ImmunoTherapy of Cancer, 13(11). https://doi.org/10.1136/jitc-2025-012225

MLA:

Guardamagna, Mora, et al. "International real-world study of combination immunotherapy sequences in metastatic melanoma." Journal for ImmunoTherapy of Cancer 13.11 (2025).

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