Clinical markers of immunotherapy outcomes in advanced sarcoma.


Journal

BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800

Informations de publication

Date de publication:
07 Apr 2023
Historique:
received: 18 10 2022
accepted: 21 03 2023
medline: 11 4 2023
entrez: 7 4 2023
pubmed: 8 4 2023
Statut: epublish

Résumé

Despite immunotherapy's promise in oncology, its use for sarcoma remains challenging. There are no sarcoma-specific biomarkers for immune checkpoint inhibitors (ICI). Previously, we reported our institutional experience highlighting ICI activity in 29 patients with sarcoma. In this study, we explore responses to ICI based on ICI regimen and other covariates to identify significant clinical factors in advanced sarcoma outcomes. Patients in The Ohio State University Sarcoma Clinics were enrolled in the Sarcoma Retrospective ICI database from January 1, 2015 through November 1, 2021. Data included treatment regimen (single-agent ICI or ICI + combination) along with clinical covariates. ICI + combination was further categorized into ICI + medication, ICI + radiation, ICI + surgery, or ICI + multiple (more than 2 modalities). Statistical analysis included log-rank tests and proportional hazard regression. The primary objective was to evaluate overall survival (OS) and progression-free survival (PFS). Of the patients in the database, 135 met inclusion criteria. We demonstrated improved OS in patients treated with ICI + combination (p = 0.014, median 64 weeks), but no effect on PFS (p = 0.471, median 31 weeks). Patients with a documented immune-related adverse event (irAE) of dermatitis had improved OS, but only in the ICI + combination cohort (p = 0.021). Patients who received single-agent ICI and whose change in the neutrophil-to-lymphocyte ratio (NLR) was less than 5 had an improved OS (p = 0.002); this was not seen in patients who received ICI + combination therapy (p = 0.441). There were no differences in OS based on age, gender, histology, or subcategories of ICI + combination. This was not the case for PFS; patients who received any ICI regimen and were younger than 70 had a worse PFS (p = 0.036) compared with their older counterparts in this dataset. Patients who developed an irAE, specifically colitis (p = 0.009), hepatitis (p = 0.048), or dermatitis (p = 0.003), had an improved PFS. There were no differences in PFS based on ICI regimen (or subcategories of ICI + combination), gender, histology, change in NLR, or grade of irAE. This retrospective study demonstrates that ICI + combination therapy can improve OS in some patients with advanced sarcoma. This is consistent with our prior results of ICI in sarcoma.

Sections du résumé

BACKGROUND BACKGROUND
Despite immunotherapy's promise in oncology, its use for sarcoma remains challenging. There are no sarcoma-specific biomarkers for immune checkpoint inhibitors (ICI). Previously, we reported our institutional experience highlighting ICI activity in 29 patients with sarcoma. In this study, we explore responses to ICI based on ICI regimen and other covariates to identify significant clinical factors in advanced sarcoma outcomes.
METHODS METHODS
Patients in The Ohio State University Sarcoma Clinics were enrolled in the Sarcoma Retrospective ICI database from January 1, 2015 through November 1, 2021. Data included treatment regimen (single-agent ICI or ICI + combination) along with clinical covariates. ICI + combination was further categorized into ICI + medication, ICI + radiation, ICI + surgery, or ICI + multiple (more than 2 modalities). Statistical analysis included log-rank tests and proportional hazard regression. The primary objective was to evaluate overall survival (OS) and progression-free survival (PFS).
RESULTS RESULTS
Of the patients in the database, 135 met inclusion criteria. We demonstrated improved OS in patients treated with ICI + combination (p = 0.014, median 64 weeks), but no effect on PFS (p = 0.471, median 31 weeks). Patients with a documented immune-related adverse event (irAE) of dermatitis had improved OS, but only in the ICI + combination cohort (p = 0.021). Patients who received single-agent ICI and whose change in the neutrophil-to-lymphocyte ratio (NLR) was less than 5 had an improved OS (p = 0.002); this was not seen in patients who received ICI + combination therapy (p = 0.441). There were no differences in OS based on age, gender, histology, or subcategories of ICI + combination. This was not the case for PFS; patients who received any ICI regimen and were younger than 70 had a worse PFS (p = 0.036) compared with their older counterparts in this dataset. Patients who developed an irAE, specifically colitis (p = 0.009), hepatitis (p = 0.048), or dermatitis (p = 0.003), had an improved PFS. There were no differences in PFS based on ICI regimen (or subcategories of ICI + combination), gender, histology, change in NLR, or grade of irAE.
CONCLUSIONS CONCLUSIONS
This retrospective study demonstrates that ICI + combination therapy can improve OS in some patients with advanced sarcoma. This is consistent with our prior results of ICI in sarcoma.

Identifiants

pubmed: 37029351
doi: 10.1186/s12885-023-10758-w
pii: 10.1186/s12885-023-10758-w
pmc: PMC10080913
doi:

Substances chimiques

Antineoplastic Agents, Immunological 0
Biomarkers 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

326

Subventions

Organisme : NIH HHS
ID : P30CA016058, K12 CA133250
Pays : United States

Informations de copyright

© 2023. The Author(s).

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Auteurs

Marium Husain (M)

Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, 1800 Cannon Drive, Suite 1240C, 43210, Columbus, OH, USA.

Dionisia Quiroga (D)

Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, 1800 Cannon Drive, Suite 1240C, 43210, Columbus, OH, USA.

Han Gil Kim (HG)

Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, 1800 Cannon Drive, Suite 1240C, 43210, Columbus, OH, USA.

Scott Lenobel (S)

Department of Radiology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.

Menglin Xu (M)

Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, 1800 Cannon Drive, Suite 1240C, 43210, Columbus, OH, USA.

Hans Iwenofu (H)

Department of Pathology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.

James L Chen (JL)

Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, 1800 Cannon Drive, Suite 1240C, 43210, Columbus, OH, USA.

Claire Verschraegen (C)

Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, 1800 Cannon Drive, Suite 1240C, 43210, Columbus, OH, USA.

David Liebner (D)

Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, 1800 Cannon Drive, Suite 1240C, 43210, Columbus, OH, USA.

Gabriel Tinoco (G)

Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, 1800 Cannon Drive, Suite 1240C, 43210, Columbus, OH, USA. Gabriel.Tinoco@osumc.edu.

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Classifications MeSH