Evidence map›Paper›PMID 40987493›Full record

ArticleJournal for immunotherapy of cancer2025

HLA-A*01:01-B*08:01-C*07:01 is linked to early-onset immune checkpoint inhibitor-induced myositis and myocarditis.

Leonie Müller-Jensen, Lukas Flatz, Omar Hasan Ali, Raphael Mohr, Nils Lachmann, Lukas Mödl, Matthias Endres, Wolfgang Boehmerle, Petra Huehnchen

Abstract readMulticenter Study
In one paragraph

Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
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  6. 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

9 authors.

Leonie Müller-JensenDepartment of Neurology with Experimental Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany leonie.mueller-jensen@charite.de.ORCID http://orcid.org/0000-0002-6388-9375
Lukas FlatzDepartment of Dermatology, Eberhard Karls University of Tuebingen, Tuebingen, Germany.ORCID http://orcid.org/0000-0001-9683-8390
Omar Hasan AliInstitute of Immunobiology, Medical Research Center, Kantonsspital St. Gallen, St. Gallen, Switzerland.ORCID http://orcid.org/0000-0001-5185-7520
Raphael MohrDepartment of Hepatology & Gastroenterology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0003-2403-4275
Nils LachmannInstitute of Transfusion Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0002-2081-3098
Lukas MödlInstitute of Biometry and Clinical Epidemiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Matthias Endres *Department of Neurology with Experimental Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0001-6520-3720
Wolfgang Boehmerle *Department of Neurology with Experimental Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0001-7195-3894
Petra Huehnchen *Department of Neurology with Experimental Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0002-6825-7270

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundImmune-related myotoxicity (irM), including irMyocarditis and irMyositis, is a severe complication of immune checkpoint inhibitors (ICIs). Markers to identify patients at risk are missing. In this retrospective multicenter cohort study, we aimed to determine whether specific human leukocyte antigen (HLA) variants are associated with irM.

methodsTwenty patients with irMyocarditis and/or irMyositis (median age (IQR), 67 (60-73) years; 7/20 female) and 60 cancer controls (CC) without immune-related adverse events (median age (IQR), 68 (62-74) years; 26/60 female) presenting to Charité - Universitätsmedizin Berlin, Germany, or Kantonsspital St. Gallen, Switzerland, between September 2017 and June 2024, were included. As a second control cohort, we used HLA data from a historic dataset of 5.1×10⁶ German healthy donors (G-HD). Allele frequencies (AF) of two-field HLA types were compared between patients with irM, CC, and G-HD using logistic regression and two-sided z-tests of odds ratios (OR).

resultsComparison of single HLA AF between patients with irM and G-HD revealed moderate associations for irM with B*07:02 (OR 2.29; 95% CI 1.12 to 4.69; p=0.023), B*40:01 (OR 2.75; 95% CI 1.08 to 7.02; p=0.035), C*03:04 (OR 2.46; 95% CI 1.09 to 5.56; p=0.031), DPB1*04:02 (OR 2.37; 95% CI 1.16 to 4.85; p=0.018), and DQB1*06:02 (OR 2.28; 95% CI 1.12 to 4.67; p=0.024). No statistically significant differences were observed between patients with irM and CC. By contrast, multi-allelic HLA analysis identified a strong association between HLA-A*01:01-B*08:01-C*07:01, a component of the 8.1 ancestral haplotype (8.1 AH), and

conclusionsOur results provide first evidence that early-onset irM with myocardial injury is linked to HLA-A*01:01-B*08:01-C*07:01, a component of the 8.1 AH, which is associated with various autoimmune diseases including idiopathic myopathies. If validated in larger cohorts, pretreatment screening for HLA-A*01:01-B*08:01-C*07:01 may help identify patients at risk of early-onset and severe irM.

Indexed as

HLA-A AntigensImmune Checkpoint InhibitorsMyocarditisMyositisAgedFemaleHumansMaleMiddle AgedRetrospective StudiesHLA-A AntigensImmune Checkpoint InhibitorsHLAimmune checkpoint inhibitorimmune related adverse event - irAEimmunotherapymyositis

Identifiers

PMID40987493
PMCPMC12458757

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Registered trials

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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.