Evidence map›Paper›PMID 42082273›Full record

ArticleJournal for immunotherapy of cancer2026

Discontinuation of combo immunotherapy and outcome of patients with melanoma brain metastases.

Mario Mandalà, Monica F Chen, Ryan J Sullivan, Maria Chiara Sergi, Michael Postow, Aleigha R Lawless, Derek Effiom, Tobias Peres, Paul C Lorigan, Patricio Serra-Bellver and 35 more

Abstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

45 authors.

Mario Mandalà *Unit of Medical Oncology, University of Perugia, Perugia, Italy mario.mandala@unipg.it.ORCID http://orcid.org/0000-0001-8846-8959
Monica F Chen *Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Ryan J Sullivan *Mass General Brigham, Boston, Massachusetts, USA.ORCID http://orcid.org/0000-0001-5344-6645
Maria Chiara SergiSan Paolo Hospital, Bari, Apulia, Italy.
Michael PostowDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.ORCID http://orcid.org/0000-0002-3367-7961
Aleigha R LawlessMass General Brigham, Boston, Massachusetts, USA.
Derek EffiomMass General Brigham, Boston, Massachusetts, USA.
Tobias PeresThe Royal Marsden NHS Foundation Trust, London, UK.
Paul C LoriganThe University of Manchester, Manchester, England, UK.
Patricio Serra-BellverThe University of Manchester, Manchester, England, UK.
Reinhard DummerDepartment of Dermatology, University Hospital Zurich, Zürich, Switzerland.ORCID http://orcid.org/0000-0002-2279-6906
Teresa AmaralDermato-Oncology, Eberhard Karls Universitat Tubingen, Tubingen, Germany.
Marie-Lena RaschDepartment of Dermatology, Eberhard Karls Universitat Tubingen, Tübingen, Germany.ORCID http://orcid.org/0000-0003-0173-9985
Diana GiannarelliEpidemiology and Biostatistics, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy.ORCID http://orcid.org/0000-0002-6085-1195
Maria Grazia VitaleNational Cancer Institute IRCCS Pascale Foundation, Naples, Campania, Italy.
Hildur HelgadottirDepartment of Oncology, Karolinska University Hospital, Stockholm, Sweden.
Caroline RobertGustave Roussy, Villejuif, France.ORCID http://orcid.org/0000-0002-9493-0238
Martina UbaldiUnit of Medical Oncology, University of Perugia, Perugia, Italy.
Douglas B JohnsonVanderbilt University Medical Center, Nashville, Tennessee, USA.
Michele Del VecchioDepartment of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Alice IndiniDepartment of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.ORCID http://orcid.org/0000-0001-8686-4106
Karijn P M SuijkerbuijkDepartment of Medical Oncology, Utrecht University, Utrecht, Utrecht, Netherlands.ORCID http://orcid.org/0000-0003-3604-5430
Paul NathanMount Vernon Cancer Centre, Northwood, UK.
Thomas CarterMount Vernon Cancer Centre, Northwood, UK.
Bart NeynsMedische Oncologie, Vrije Universiteit Brussel, Brussels, Brussels, Belgium.ORCID http://orcid.org/0000-0003-0658-5903
Iris DirvenDepartment of Medical Oncology, Universitair Ziekenhuis Brussel, Brussels, Brussels, Belgium.
Ines Pires da SilvaMelanoma Institute Australia, North Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0003-3540-8906
Alexander Maxwell MenziesMelanoma Institute Australia, North Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0001-5183-7562
Lisa ZimmerDermatology, University of Duisburg-Essen, Essen, Germany.ORCID http://orcid.org/0000-0002-3680-3521
Elisabeth LivingstoneDermatology, University of Duisburg-Essen, Essen, Germany.
Roberta DepenniDepartment of Oncology, Hematology, University of Modena and Reggio Emilia, Modena, Italy.
Katharina KählerDepartment of Dermatology, University Hospital Schleswig Holstein, Kiel, Germany.
Axel HauschildDepartment of Dermatology, University Hospital Schleswig Holstein, Kiel, Germany.
Francesco SpagnoloGenoa National Institute for Cancer Research, Genoa, Liguria, Italy.
Anna Maria Di GiacomoUniversity of Siena, Siena, Italy.
Ana AranceMedical Oncology, Hospital Clínic Barcelona, Barcelona, Spain.ORCID http://orcid.org/0000-0003-2896-1957
Barbara MerelliUnit of Medical Oncology, Department of Oncology and Hematology, ASST Papa Giovanni XXIII, Bergamo, Lombardia, Italy.
Pietro QuaglinoDermatologic Clinic, Department of Medical Sciences, University of Turin, Torino, Piemonte, Italy.
Ernesto RossiFondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Lazio, Italy.
Marco TucciMedical Oncology Unit, University of Bari, Policlinico Hospital of Bari, Bari, Puglia, Italy.
Michele GuidaOncology Department, Giovanni Paolo II Cancer Institute IRCCS, Bari, Apulia, Italy.ORCID http://orcid.org/0000-0001-8411-0319
Eva Muñoz-CouseloOncology Department, Vall d'Hebron University Hospital, Barcelona, Spain.
Georgina V Long *Melanoma Institute Australia, Wollstonecraft, New South Wales, Australia.
James Larkin *The Royal Marsden NHS Foundation Trust, London, UK.
Paolo A Ascierto *Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy.ORCID http://orcid.org/0000-0002-8322-475X

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

backgroundNivolumab plus ipilimumab (COMBO) is the standard treatment for asymptomatic melanoma brain metastases (MBM), but current guidelines do not provide specific recommendations for treatment discontinuation in responding patients. This study aimed to evaluate outcomes after COMBO discontinuation within 24 months and the role of continuing treatment beyond 24 months.

methodsPatients with MBM treated with COMBO who discontinued treatment within 24 months for reasons other than disease progression or continued beyond this time point were retrieved. Overall survival (OS), objective response, progression-free survival (PFS) and toxicities were analyzed.

results465 patients were included: 392 discontinued COMBO within 24 months, while 73 continued beyond 24 months. Treatment was discontinued due to complete response (CR, n=47), partial response (PR, n=45), stable disease (SD, n=12), toxicity after SD (n=59), toxicity after CR (n=99), or toxicity after PR (n=130). At multivariable analysis, the line of treatment (>first vs first: HR 2.65 (1.62-4.32)), the immune-related adverse events (irrespective of anti-tumor necrosis factor-alpha) (HR 0.18 (0.07-0.42)); COMBO discontinuation after CR (HR 0.15 (0.05-0.40)), or PR (HR 0.08 (0.03-0.26)), as well as stopping due to toxicity after CR (HR 0.14 (0.07-0.27)) or PR (HR 0.51 (0.32-0.82)), were associated with OS. Notably, at a median follow-up of 51 months (IQR 31-70), patients with CR/PR who discontinued COMBO within 24 months had PFS and OS comparable to those who continued treatment beyond this time point. 4-year OS exceeded 83% in patients discontinuing COMBO after CR, PR, or toxicity following CR, compared with 66.4% in those discontinuing due to toxicity after PR; median PFS was not reached in the former groups but was 18.6 months in the toxicity after PR group.

conclusionDiscontinuation of COMBO within 24 months appears safe in patients with CR and in selected cases of PR, with no survival disadvantage versus prolonged therapy.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBrain NeoplasmsImmunotherapyIpilimumabMelanomaNivolumabAdultAgedFemaleHumansMaleMiddle AgedTreatment InterruptionTreatment OutcomeIpilimumabNivolumabImmunotherapySkin Cancer

Identifiers

PMID42082273
PMCPMC13141176

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.