Steroid-refractory immune mediated hepatitis managed with budesonide in patients with metastatic melanoma: proof of concept and literature review

The Oncologist, Journal Year: 2025, Volume and Issue: 30(1)

Published: Jan. 1, 2025

Abstract Immune checkpoint inhibitors (ICIs) have advanced the treatment of metastatic melanoma. However, some patients develop ICI-associated toxicities like hepatitis (ie, immune-mediated hepatitis; IMH). Although these usually resolve with steroids, steroid-refractory events may occur, which be a major source morbidity and mortality without obviously defined algorithms. Herein, we present 2 melanoma who had IMH that was only partially mycophenolate-responsive, but fully resolved budesonide. The case suggests budesonide is potential option to treat refractory standard treatments, further investigation in larger series needed identify most optimal setting for use.

Language: Английский

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Immune‐Mediated Liver Injury From Checkpoint Inhibitor: An Evolving Frontier With Emerging Challenges

Liver International, Journal Year: 2025, Volume and Issue: 45(2)

Published: Jan. 27, 2025

ABSTRACT Over the past decade, immune checkpoint inhibitors (ICIs) have transformed treatment of cancer, though they come with risk immune‐related adverse (irAEs) events such as hepatotoxicity or Immune‐mediated Liver Injury from Checkpoint Inhibitors (ILICI). ILICI is a serious irAE that, when severe, requires cessation ICI and initiation immunosuppression. Cytotoxic T Lymphocytes (CTLs) play central role in ILICI; however, are just part picture immunotherapy broadly impacts all aspects microenvironment can directly indirectly activate innate adaptive cells. Clinically, our understanding this entity grows, we encounter new challenges. The presentation heterogeneous respect to latency, pattern injury (hepatitis vs. cholangitis) severity. This review focuses on knowledge regarding factors, including refractory steroids. An emerging topic, possibility rechallenge while accepting some risk, patients who experience but require immunotherapy, also discussed. provides an update current knowns unknowns highlights several gaps where studies needed.

Language: Английский

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Toxicity in the era of immune checkpoint inhibitor therapy

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 23, 2024

Immune checkpoint inhibitors (ICIs) reinvigorate anti-tumor immune responses by disrupting co-inhibitory molecules such as programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4). Although ICIs have had unprecedented success become the standard of care for many cancers, they are often accompanied off-target inflammation that can occur in any organ system. These related adverse events (irAEs) require steroid use and/or cessation ICI therapy, which both lead to cancer progression. irAEs common, detailed molecular mechanisms underlying their development still elusive. To further our understanding develop effective treatment options, there is pressing need preclinical models recapitulating clinical settings. In this review, we describe current implications ICI-induced skin toxicities, colitis, neurological endocrine pneumonitis, arthritis, myocarditis along with management.

Language: Английский

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Granulomatous liver diseases

Hepatology Communications, Journal Year: 2024, Volume and Issue: 8(4)

Published: March 18, 2024

A granuloma is a discrete collection of activated macrophages and other inflammatory cells. Hepatic granulomas can be manifestation localized liver disease or part systemic process, usually infectious autoimmune. biopsy required for the detection evaluation granulomatous diseases. The prevalence on varies from 1% to 15%. They may an incidental finding in asymptomatic individual, they represent hepatitis with potential progress failure, chronic disease, cirrhosis. This review focuses pathogenesis, histological features diseases, most common etiologies, knowledge that essential timely diagnosis intervention.

Language: Английский

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A Real-World Comparison of the Safety Profile for Immune Checkpoint Inhibitors in Oncology Patients

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(2), P. 388 - 388

Published: Jan. 9, 2025

Background/Objectives: Owing to the growing use of immune checkpoint inhibitors (ICIs) in treatment cancer, a wide spectrum toxicity has arisen among cancer patients. Yet, limited ICI toxicity-related research is currently conducted our region. Methods: This retrospective observational study on adult patients who received at least one cycle single therapy. Toxicity profiles different monotherapies were described and compared, their association with risk factors was assessed. SPSS version 28 used for statistical analyses, p < 0.05 considered statistically significant. Results: A total 428 treated anti-PD1 (nivolumab [n = 221, 51.6%] pembrolizumab 126, 29.5%]) or anti-PD-L1 (atezolizumab 78, 18.2%] durvalumab 3, 0.7%]). Pneumonia most common complication (10%), followed by acute kidney injury (AKI; 8.2%) hepatitis (7.9%). The proportion cases significantly higher atezolizumab compared nivolumab-, pembrolizumab-, durvalumab-treated (17.95% vs. 7.7% 2.4% 0.0%, respectively; 0.001). Gastrointestinal (colitis) detected 3.3% significant difference between groups (4.5%, 1.6%, 1.3%, 33.3% nivolumab, pembrolizumab, atezolizumab, durvalumab, 0.008). Cardiac complications occurred 1.2% (0.5% 3.8% none (p 0.001)). Musculoskeletal side effects, including both arthralgia fatigue, most-reported effects 39.5% patients, complainers only nivolumab (7.7%) other (0%, 2.6%, 0% respectively, 0.007). Hepatic, cardiovascular, hematological, respiratory, renal, gastrointestinal complications, thyroid dermatological found occur weeks 6, 7.5, 8, 10, 10.5, 12 after initiation, no groups. Despite that, AKI tended earlier (week 2, 0.084) 0.062), comparators. female gender history increase odds hepatic [OR 2.71; 95% CI 1.07-6.85, OR 11.14; 3.46-35.88, respectively]. Previous exposure therapy developing pneumonia 3.08; 1.12-8.85]. Having hematological malignancy influenced positively (either neutropenia thrombocytopenia) solid malignancies when 17.18; 4.06-72.71]. Finally, associate nausea/vomiting fatigue secondary administration 2.08; 1.34-3.21, 1.65; 1.09-2.51, On hand, previous reduce having 0.344; 0.121-0.974]. Conclusions: Treatment associated effects. Several have been identified impact occurrence. toxicities influencing should be recognized clinical practice, as this could help individualizing therapeutics regimens avoiding interruption.

Language: Английский

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Case report: Multi-organ injuries induced by tislelizumab

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

Published: Feb. 4, 2025

The use of immune checkpoint inhibitors (ICIs) often develops immune-related adverse events (irAEs). However, irAEs-induced multi-organ injuries remain a rare event. We herein report case induced by tislelizumab in lung squamous cell carcinoma (LUSC) patient. A 68-year-old man had undergone neoadjuvant chemotherapy with paclitaxel, carboplatin, and tislelizumab. He presented 1-month history nausea poor appetite after the second dose therapy. During investigations, rhabdomyolysis, liver, kidney, thyroid damage were detected. After multi-disciplinary consultation, related to ICIs (striated muscle, thyroid) considered result from cumulated irAEs patient was treated levothyroxine, methylprednisolone, intravenous immunoglobulins, continuous renal replacement treatment, recovered discharged hospital. multiple organ damage, not single immunity treatment reactions, relatively rare. In clinical work, are likely single-system disorder many kinds attention need be combined risk multi-system damage.

Language: Английский

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Incidence and management of hepatic immune‑related adverse events in advanced urologic cancers treated with immune checkpoint inhibitors: A multicenter retrospective study

Oncology Letters, Journal Year: 2025, Volume and Issue: 29(4), P. 1 - 11

Published: March 4, 2025

The present study aimed to evaluate the incidence, characteristics and management of hepatic immune‑related adverse events (irAEs) in patients with advanced or metastatic urothelial carcinoma (UC) renal cell (RCC) receiving immune checkpoint inhibitors (ICIs). Data regarding demographics, ICI regimens irAEs from 213 UC RCC ICIs between February 2018 September 2023 at three tertiary medical centers (Inje University Busan Paik Hospital, Busan, South Korea; Dongnam Institute Radiological Medical Sciences Cancer Center, Pusan National Korea) Korea were collected retrospectively analyzed. Hepatic graded using Common Terminology Criteria for Adverse Events version 5.0 classified based on R value patterns. Among evaluated, 76 (35.6%) experienced least one irAE, whereas 48 (22.5%) developed irAEs. median onset time was 6.5 weeks, incidence rates being higher combination therapies than monotherapies (31.8 vs. 18.3%; P=0.014). Furthermore, 72.9 27.1% had grade 1‑2 3‑4 irAEs, respectively. patterns liver toxicity included cholestatic (35.4%), mixed (35.4%) hepatocellular (29.2%). All irAE recovered supportive treatment without discontinuation corticosteroids use. 13 ≥3 12 high‑dose corticosteroids, while 1 died due fulminant hepatitis. are common urologic cancers who treated ICIs, particularly therapies. Most cases have low‑grade that manageable discontinuation; however, severe require prompt recognition corticosteroids. These findings emphasize importance regular function monitoring appropriate strategies cancer therapy.

Language: Английский

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4-Methylumbelliferone, an Inhibitor of Hyaluronan Synthase, Prevents the Development of Oncological, Inflammatory, Degenerative, and Autoimmune Diseases

Biochemistry (Moscow), Journal Year: 2025, Volume and Issue: 90(1), P. 1 - 18

Published: Jan. 1, 2025

Language: Английский

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PD-1/PD-L1 immune checkpoint therapy demonstrates favorable safety profile in patients with autoimmune and cholestatic liver disease

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 10, 2024

Introduction Immune checkpoint inhibitors (ICI) have revolutionized the treatment of many malignancies in recent years. However, immune−related adverse events (irAE) are a frequent concern clinical practice. The safety profile ICI for patients diagnosed with autoimmune and cholestatic liver disease (AILD) remains unclear. Due to this uncertainty, these were excluded from trials withheld patient group. In retrospective multicenter study, we assessed AILD. Methods We contacted tertiary referral hospitals identification AILD under Europe via European Reference Network on Hepatological Diseases (ERN RARE-LIVER). Fourteen centers contributed data being treated ICI, another three did not treat due fear irAEs. Results 22 could be identified. Among patients, 12 had primary biliary cholangitis (PBC), five sclerosing (PSC), four hepatitis (AIH), one an AIH-PSC variant syndrome. Eleven hepatobiliary cancers other 11 presented non-hepatic tumors. applied ICIs atezolizumab (n=7), durvalumab (n=5), pembrolizumab (n=4), nivolumab spartalizumab (n=1), case combined immunotherapy plus ipilimumab. eight who grade 1 or 2 irAEs, demonstrated Cases grades ≥ 3 irAEs reported. No significant changes tests observed during first year after start ICI. Discussion This study demonstrates that PD-1/PD-L1 appear safe Further studies more potent dual immune therapy needed. conclude should categorically

Language: Английский

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Rechallenge in idiosyncratic drug-induced liver injury: An analysis of cases in two large prospective registries according to existing definitions

Pharmacological Research, Journal Year: 2024, Volume and Issue: 203, P. 107183 - 107183

Published: April 15, 2024

Data on positive rechallenge in idiosyncratic drug-induced liver injury (DILI) are scarce. We aim to analyse the clinical presentation, outcome and drugs associated with two DILI registries. Cases from Spanish Latin American registries were included. Demographics, characteristics of cases according CIOMS/RUCAM current definitions analysed. Of 1,418 patients DILI, 58 had (4.1%). Patients shorter duration therapy (p=0.001) latency (p=0.003). In rechallenge, aspartate transaminase levels increased (p=0.026) showed a prolonged time recovery (p=0.020), albeit no differences seen terms fatal outcomes. The main drug implicated was amoxicillin-clavulanate (17%). majority re-exposure events unintentional (71%). Using both existing there four which exclusively fulfilled criteria five only meet historical definition. All irrespective pattern damage, either alanine (ALT) ≥3 times upper limit normal (ULN) and/or alkaline phosphatase (ALP) ≥2 ULN. Episodes characterised by latency, longer resolution, but did not show an incidence outcome. Based our findings, ALT ULN ALP ULN, regardless is proposed as new definition DILI.

Language: Английский

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