Evidence map›Paper›PMID 28495807›Full record

ArticleThe oncologist2017

Neurologic Serious Adverse Events Associated with Nivolumab Plus Ipilimumab or Nivolumab Alone in Advanced Melanoma, Including a Case Series of Encephalitis.

James Larkin, Bartosz Chmielowski, Christopher D Lao, F Stephen Hodi, William Sharfman, Jeffrey Weber, Karijn P M Suijkerbuijk, Sergio Azevedo, Hewei Li, Daniel Reshef and 2 more

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In one paragraph

Article in The oncologist, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
145citing papers in PubMed, 9 pooled it
–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

145 citing papers in PubMed, 9 syntheses or guidelines pooled it.

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  17. Pain spectrum in immune checkpoint inhibitor-related adverse events: evolution, characteristics and management challenges based on bibliometrics.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026
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85 more citing papers are in PubMed but not listed here.

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

12 authors.

James LarkinThe Royal Marsden, London, United Kingdom James.larkin@rmh.nhs.uk.
Bartosz ChmielowskiUniversity of California Los Angeles Medical Center, Santa Monica, California, USA.
Christopher D LaoUniversity of Michigan, Ann Arbor, Michigan, USA.
F Stephen HodiDana-Farber Cancer Institute, Boston, Massachusetts, USA.
William SharfmanSidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, Maryland, USA.
Jeffrey WeberNew York University Langone Medical Center, New York, New York, USA.
Karijn P M SuijkerbuijkUniversity Medical Center Utrecht Cancer Center, Utrecht, Netherlands.
Sergio AzevedoHospital Mae de Deus, Porto Alegre, Brazil.
Hewei LiBristol-Myers Squibb, Princeton, New Jersey, USA.
Daniel ReshefBristol-Myers Squibb, Princeton, New Jersey, USA.
Alexandre AvilaBristol-Myers Squibb, Princeton, New Jersey, USA.
David A ReardonDana-Farber Cancer Institute, Boston, Massachusetts, USA.

Funding

Rational Sequencing of PD-1 and CTLA-4 Antibodies in Metastatic MelanomaR01CA175732 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI WEBER, JEFFREY S · 2013 to 2017
$1.7M
NCI NIH HHS R01 CA175732
6 · The paper itself

Abstract

backgroundDespite unprecedented efficacy across multiple tumor types, immune checkpoint inhibitor therapy is associated with a unique and wide spectrum of immune-related adverse events (irAEs), including neurologic events ranging from mild headache to potentially life-threatening encephalitis. Here, we summarize neurologic irAEs associated with nivolumab and ipilimumab melanoma treatment, present cases of treatment-related encephalitis, and provide practical guidance on diagnosis and management.

methodsWe searched a Global Pharmacovigilance and Epidemiology database for neurologic irAEs reported over an 8-year period in patients with advanced melanoma receiving nivolumab with or without ipilimumab from 12 studies sponsored by Bristol-Myers Squibb. Serious neurologic irAEs were reviewed, and relationship to nivolumab or ipilimumab was assigned.

resultsIn our search of 3,763 patients, 35 patients (0.93%) presented with 43 serious neurologic irAEs, including neuropathy (

conclusionBoth oncologists and neurologists need to be aware of signs and symptoms of serious but uncommon neurologic irAEs associated with checkpoint inhibitors. Prompt diagnosis and management using an established algorithm are critical to minimize serious complications from these neurologic irAEs. IMPLICATIONS FOR PRACTICE: With increasing use of checkpoint inhibitors in cancer, practicing oncologists need to be aware of the potential risk of neurologic immune-related adverse events and be able to provide prompt treatment of this uncommon, but potentially serious, class of adverse events. We summarize neurologic adverse events related to nivolumab alone or in combination with ipilimumab in patients with advanced melanoma from 12 studies and examine in depth 6 cases of encephalitis. We also provide input and guidance on the existing neurologic adverse events management algorithm for nivolumab and ipilimumab.

Indexed as

AgedAntibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsClinical Trials as TopicDrug-Related Side Effects and Adverse ReactionsEncephalitisFemaleHumansIpilimumabMaleMelanomaMiddle AgedNervous System DiseasesNivolumabAntibodies, MonoclonalIpilimumabNivolumabCase seriesEncephalitisImmune checkpoint inhibitorsImmune‐related adverse eventsMelanomaNeurologic adverse events

Identifiers

PMID28495807
PMCPMC5469590

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.