Evidence map›Paper›PMID 40973222›Full record

ArticleJournal for immunotherapy of cancer2025

Clonal hematopoiesis is associated with reduced response to atezolizumab in non-small cell lung cancer.

Vylyny Chat, Kipper Fletez-Brant, Minu Srivastava, Barzin Nabet, Ira Mellman, Mark I McCarthy, Christian Hammer

Abstract read
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 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Trial
  2. 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

7 authors.

Vylyny ChatGenentech Inc, South San Francisco, California, USA chatv@gene.com.ORCID http://orcid.org/0009-0006-6810-6612
Kipper Fletez-BrantGenentech Inc, South San Francisco, California, USA.
Minu SrivastavaGenentech Inc, South San Francisco, California, USA.ORCID http://orcid.org/0009-0000-3827-9180
Barzin NabetGenentech Inc, South San Francisco, California, USA.ORCID http://orcid.org/0000-0002-4824-3533
Ira MellmanGenentech Inc, South San Francisco, California, USA.
Mark I McCarthyGenentech Inc, South San Francisco, California, USA.
Christian HammerGenentech Inc, South San Francisco, California, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe acquisition of somatic mutations associated with the expansion of certain hematopoietic stem cells is known as clonal hematopoiesis (CH). Despite evidence of CH association with age-related pro-inflammatory diseases, little is known about its role in the response to antitumor immune modulatory therapies such as immune-checkpoint inhibition (ICI). In this report, we characterize the effect of CH on ICI objective response in non-small cell lung cancer (NSCLC).

methodsWe performed baseline blood-derived whole-exome sequencing of 1,281 patients with NSCLC from five anti-programmed death ligand-1 (PD-L1) trials (FIR, POPLAR, IMpower110, IMpower150, and IMpower131). Multivariable logistic regression adjusting for age, sex, and smoking history was used to model the odds of being a non-responder in each trial, and random effects meta-analyses were performed in anti-PD-L1 and comparator arms.

resultsCH carriage, defined as the presence of CH with variant allele fraction≥2%, was associated with adverse objective response across the anti-PD-L1 treatment arms (OR=1.69 (95% CI 1.08 to 2.63); p=0.02). No association was observed in the comparator arms (OR=0.61 (95% CI 0.31 to 1.21); p=0.16). CH carriers had lower absolute leukocyte counts (p

conclusionsIn this report, we provide evidence of the adverse impact of CH on ICI treatment objective response in NSCLC, highlighting CH as a potential predictive biomarker for patient stratification in ICI. Further experimental validation is needed to better understand the mechanism of action behind this reduction in ICI efficacy.

Indexed as

Antibodies, Monoclonal, HumanizedCarcinoma, Non-Small-Cell LungClonal HematopoiesisImmune Checkpoint InhibitorsLung NeoplasmsAgedFemaleHumansMaleMiddle AgedAntibodies, Monoclonal, HumanizedatezolizumabImmune Checkpoint InhibitorsImmune Checkpoint InhibitorLung Cancer

Identifiers

PMID40973222
PMCPMC12458721

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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.