Development of a Predictive Model for Classifying Immune Checkpoint Inhibitor‐Induced Liver Injury Types

JGH Open, Journal Year: 2025, Volume and Issue: 9(4)

Published: April 1, 2025

ABSTRACT Aims Immune checkpoint inhibitors (ICIs) have transformed cancer therapy; however, they are associated with ICI‐induced liver injury (ICI‐LI), which manifests as hepatocellular, mixed, or cholestatic patterns variable treatment responses. This study aimed to develop and validate a predictive model identify ICI‐LI type using clinical data available at ICI initiation. Methods A retrospective analysis of 297 patients was conducted. Baseline were analyzed univariate multivariate logistic regression predict types in the training validation cohorts. developed validated receiver operating characteristic (ROC) curve analysis. Results Multivariate cohort identified male sex (odds ratio [OR]: 3.33, 95% confidence interval [CI]: 1.57–7.06, p = 0.002), serum albumin levels (OR: 0.42, CI: 0.19–0.91, 0.027), alanine aminotransferase (ALT) 0.97, 0.94–0.99, 0.015) significant predictors, along regimen selected Akaike information criterion. The model, expressed 1/{1 + (−(5.02 1.20 × (sex [F:0, M:1])) − 0.87 [g/dL] 0.03 ALT [U/L] 0.9 (drug [non‐anti‐cytotoxic T lymphocyte antigen 4 (CTLA‐4) related regimen:0, anti‐CTLA‐4 regimen:1]))}, achieved an area under ROC (AUROC) 0.73 (95% 0.63–0.82) cohort. At cut‐off 0.86, sensitivity 60.3%, specificity 74.4%, positive value 92.3%, negative 26.9%. In cohort, AUROC 0.752 0.476–1.00). Conclusion demonstrates its utility classifying types.

Language: Английский

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Ursodeoxycholic Acid Alone Is Effective and Safe to Treat Cholestatic Checkpoint Inhibitor‐Induced Liver Injury

Liver International, Journal Year: 2025, Volume and Issue: 45(5)

Published: April 8, 2025

ABSTRACT Introduction Checkpoint Inhibitor‐induced Liver Injury (CHILI) is a frequent complication of immune checkpoint inhibitors (ICIs). Corticosteroids are the standard treatment but have many limitations. Ursodeoxycholic acid (UDCA) offers an alternative for managing cholestatic CHILI, its efficacy remains underexplored. Methods A multicenter retrospective study included 27 patients treated with first‐line UDCA monotherapy. Data were collected from diagnosis to week 52, assessing liver enzyme improvement, recurrence, and outcomes. Results alone achieved improvement in 81.5% patients, average response time 39.3 days. Among 77.8% had severe CHILI (CTCAE grade ≥ 3). Macroscopic bile duct injury was observed 37%, associated higher recurrence rates (75%, p < 0.001). Recurrent led chronic all cases. ICI rechallenge conducted 52% only 23% experiencing relapse. Conclusion monotherapy appears effective presenting viable corticosteroids. Further prospective studies warranted.

Language: Английский

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Immunotherapy in gestational trophoblastic neoplasia: advances and future directions

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 11, 2025

Gestational trophoblastic neoplasia (GTN) is a rare but aggressive malignancy that follows normal or aberrant pregnancies. Until the advent of immunotherapy in 2017, surgery and chemotherapy were standard treatment modalities, with remaining cornerstone. However, chemoresistance high-risk disease present significant challenges managing GTN. Recent advancements immunotherapy, particularly immune checkpoint inhibitors (ICIs), have offered new hope for these difficult cases. This review provides comprehensive overview mechanisms underlying ICIs GTN, explores potential synergy combining targeted therapies, such as vascular endothelial growth factor epidermal receptor inhibitors. We also provide an latest evidence on use treating focusing their effectiveness both low- cases, well chemorefractory settings. In addition, we discuss ongoing clinical trials, immune-related adverse events associated ICIs, biomarker-driven approaches, immunosuppressive tumor microenvironments, posed resistance. The future directions, including integration into regimens, personalized based biology, importance fertility preservation young patients conclusion, while remain, represents promising frontier GTN treatment, to improve outcomes more approach care

Language: Английский

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First-in-human phase I study of EMB-02, a bispecific antibody targeting PD-1 and LAG-3 in patients with advanced solid tumors

British Journal of Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

Abstract Background EMB-02 is a symmetric bispecific antibody targeting programmed cell death protein-1 and lymphocyte-activation gene 3 simultaneously. Here, we present the first-in-human study results of in patients with advanced solid tumors. Methods Patients were treated intravenous infusions at doses 6–900 mg. The primary objective was to evaluate safety tolerability determine maximum tolerated dose and/or recommended phase II dose(s). Secondary objectives included characterizing pharmacokinetic (PK) profile, assessing preliminary antitumor activity immunogenicity. Results A total 47 enrolled. All grade 3/4 treatment-emergent treatment related adverse events occurred 97.9%, 48.9%, 68.1% 12.8% patients, respectively. response rate (ORR) 6.4% clinical benefit 24 weeks (CBR-24) 25.5% overall population. CBR-24 33.3% checkpoint inhibitor (CPI)-naïve 15% CPI-treated. No clear relationship observed between efficacy PD-L1, LAG-3, or MHC expression level. Doses 360 mg higher resulted sustained saturation PD-1 receptors on circulating CD3 + T cells. Conclusions demonstrated favorable profile early signals multiple tumors, warranting further development. (NCT04618393).

Language: Английский

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Immune checkpoint inhibitors: From friend to foe

Toxicology Reports, Journal Year: 2025, Volume and Issue: 14, P. 102033 - 102033

Published: April 24, 2025

Language: Английский

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