Evidence map›Paper›PMID 40001294›Full record

ArticleThe Journal of clinical endocrinology and metabolism2025

The Risk of Adrenal Insufficiency After Treatment With Relatlimab in Combination With Nivolumab is Higher Than Expected.

Natalia Chamorro-Pareja, Alexander T Faje, Karen K Miller

Abstract read
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. 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

3 authors.

Natalia Chamorro-ParejaNeuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.ORCID 0000-0003-1354-1730
Alexander T FajeNeuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Karen K MillerNeuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.ORCID 0000-0001-9438-2449

Funding

TRAINING PROGRAM IN ENDOCRINOLOGY AND DIABETEST32DK007028 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Karen K Miller · 1986 to 2026
$18.5M
NIDDK NIH HHS T32 DK007028
6 · The paper itself

Abstract

contextAdrenal insufficiency from hypophysitis is a complication of immune checkpoint inhibitor (ICI) therapy. However, the risk associated with relatlimab, a lymphocyte-activation gene 3 inhibitor, is unknown. Relatlimab was approved in 2022 in combination with nivolumab for the treatment of unresectable or metastatic melanoma.

objectiveTo determine the prevalence, identify risk factors, and characterize the clinical presentation of central adrenal insufficiency in patients receiving relatlimab-nivolumab compared to nivolumab alone.

methodsRetrospective analysis of Mass General Brigham healthcare system patients who received relatlimab-nivolumab from 2015 to 2023 matched by age, sex, and race to individuals receiving monotherapy with nivolumab, an ICI with a risk of hypophysitis of <1%.

resultsAdrenal insufficiency was diagnosed in 10 patients (8%) after relatlimab-nivolumab administration and in 1 patient (<1%) after nivolumab monotherapy (P = .00056). Within the relatlimab-nivolumab group, median age and sex were comparable in patients who developed adrenal insufficiency compared to those who did not. The median number of doses received by subjects who developed adrenal insufficiency was 7 (4-10) compared to 3 (2-6) in those who did not (P = .03). The most common presenting symptoms were fatigue, anorexia, nausea, and vomiting. No patients were diagnosed with additional anterior pituitary hormone deficiencies or arginine vasopressin deficiency, though not all patients were evaluated for these diagnoses.

conclusionThis study is the first cohort analysis of hypophysitis in patients treated with relatlimab-nivolumab compared to nivolumab monotherapy. Combination treatment with relatlimab-nivolumab confers a significantly higher risk of developing adrenal insufficiency, likely secondary to hypophysitis, compared to nivolumab alone.

Indexed as

Adrenal InsufficiencyAntineoplastic Combined Chemotherapy ProtocolsMelanomaNivolumabAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedFemaleHumansHypophysitisImmune Checkpoint InhibitorsMaleMiddle AgedPrevalenceRetrospective StudiesAntibodies, Monoclonal, HumanizedImmune Checkpoint InhibitorsNivolumabrelatlimabcentral adrenal insufficiencyhypophysitishypopituitarismimmune checkpoint inhibitorsnivolumabrelatlimab

Identifiers

PMID40001294
PMCPMC13123525

What OpenQuestion holds

Textmetadata
LicenceTDM
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.