Characterization of risk factors and efficacy of medical management of immune-related hepatotoxicity in real-world patients with metastatic melanoma treated with immune checkpoint inhibitors

Romanski, Nicole A.; Holmstroem, Rikke Boedker; Ellebæk, Eva; Svane, Inge Marie

doi:10.1016/j.ejca.2020.02.041

Cited by 30 publications

(16 citation statements)

References 25 publications

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“…Immune-related hepatitis (IRH) is usually asymptomatic, with elevated serum transaminase or bilirubin levels. Most patients developing IRH tended to receive corticosteroid treatment ( 55 ). For patients with grade ≥3 irAEs, which are usually life-threatening, ICIs should be permanently discontinued and treatment with immunosuppressive drugs such as glucocorticoids should be commenced.…”

Section: Discussionmentioning

confidence: 99%

Immune-Related Adverse Events Predict the Efficacy of Immune Checkpoint Inhibitors in Lung Cancer Patients: A Meta-Analysis

Wang

Chen

et al. 2021

Front. Oncol.

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BackgroundImmune-related adverse events (irAEs) have been reported to be associated with the efficacy of immunotherapy. Herein, we conducted a meta-analysis to demonstrate that irAEs could predict the efficacy of immune checkpoint inhibitors (ICIs) in lung cancer patients.MethodsLiterature on the correlation between irAEs and the efficacy of immunotherapy in lung cancer patients were searched to collect the data on objective response rate (ORR), overall survival (OS), or progression-free survival (PFS) of the patients. These data were incorporated into the meta-analysis.ResultsA total of 34 records encompassing 8,115 patients were examined in this study. The irAEs occurrence was significantly associated with higher ORR {risk ratio (RR): 2.43, 95% confidence interval (CI) [2.06–2.88], p < 0.00001} and improved OS {hazard ratio (HR): 0.51, 95% CI [0.43–0.61], p < 0.00001}, and PFS (HR: 0.50, 95% CI [0.44–0.57], p < 0.00001) in lung cancer patients undergoing ICIs. Subgroup analysis revealed that OS was significantly longer in patients who developed dermatological (OS: HR: 0.53, 95%CI [0.42–0.65], p < 0.00001), endocrine (OS: HR: 0.55, 95%CI [0.45–0.67], p < 0.00001), and gastrointestinal irAEs (OS: HR: 0.58, 95%CI [0.42–0.80], p = 0.0009) than in those who did not. However, hepatobiliary, pulmonary, and high-grade (≥3) irAEs were not correlated with increased OS and PFS.ConclusionThe occurrence of irAEs in lung cancer patients, particularly dermatological, endocrine, and gastrointestinal irAEs, is a predictor of enhanced ICIs efficacy.

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Section: Discussionmentioning

confidence: 99%

Immune-Related Adverse Events Predict the Efficacy of Immune Checkpoint Inhibitors in Lung Cancer Patients: A Meta-Analysis

Wang

Chen

et al. 2021

Front. Oncol.

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“…When investigating the safety of the new therapies on real-world patients it enables clinicians and patients to understand the full measure of the treatments' potential harms. Recently, we reported potential risk factors and efficacy of clinical management on patients developing immune-related hepatitis after treatment with ICI [31]. We found that infection or antibiotic therapy could be a possible risk factor for developing immune-related hepatitis.…”

Section: Publications Based On Data From Dammedmentioning

confidence: 92%

The Danish metastatic melanoma database (DAMMED): A nation-wide platform for quality assurance and research in real-world data on medical therapy in Danish melanoma patients

Ellebæk

Svane

Haslund

et al. 2021

Cancer Epidemiology

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“…These therapies can be classified into two groups, namely, immune checkpoint inhibitors (ICIs) targeting programmed death-1 and its ligand (PD-1/PD-L1) (nivolumab and pembrolizumab) or cytotoxic T lymphocyte antigen 4 (CTLA-4) (ipilimumab); and tyrosine kinase inhibitors targeting the MAPK pathway, namely, BRAF or MEK, which are applicable for patients with tumours harbouring a BRAF V600 mutation [10e13]. The most potent combination immunotherapy of anti-PD-1 (nivolumab) and anti-CTLA-4 (ipilimumab) antibodies has achieved a 5-year-survival rate of 52%, accompanied by a high rate of toxicity [14,15]. Besides these therapeutic regimens, treatment options for patients with advanced melanoma remain limited, and targeted therapies for specific mutations in NRAS and NF1 genes are not available.…”

Section: Introductionmentioning

confidence: 99%

NF1-mutated melanomas reveal distinct clinical characteristics depending on tumour origin and respond favourably to immune checkpoint inhibitors

Thielmann

Chorti

Matull

et al. 2021

European Journal of Cancer

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Background: NF1-mutated tumours represent a small subset (10e15%) of melanomas, not sufficiently analysed in large clinical cohorts. This study investigated the largest multicentre collection of NF1-mutated melanomas to date. Methods: This study analysed a multicentre tumour tissue sample cohort from 266 patients with NF1-mutated melanoma. Targeted next-generation sequencing of the TERT promoter and 29 relevant melanoma genes was performed. Survival was compared with NF1 wildtype cohorts from the Tissue Registry in Melanoma project (n Z 432). Results: Most NF1-mutated melanoma arose in the head-and-neck region of patients >60 years. NF1 alterations were frequently inactivating, primarily non-sense, less frequently truncating mutations. Non-inactivating NF1 mutations more frequently co-occurred with activating BRAF and RAS mutations. NF1-mutated tumours had higher numbers of gene mutations and UV signature C>T and CC>TT transitions than BRAF, RAS and triple wild-type melanomas. NF1-mutated acral and mucosal melanomas harboured a different mutation signature and were frequent in women (69% and 83%, respectively), differing from nonacral cutaneous NF1-mutated melanomas (men 73%, women 27%). Overall survival in stage IV disease was comparable for patients with NF1-mutated or wild-type melanoma. However, in patients receiving first-line immune checkpoint inhibitor treatment, better median overall survival (mOS) was observed for NF1-mutated than wild-type tumours (mOS Z not reached vs mOS Z 25.82, p Z 0.0154, n Z 80 and 432, respectively). Conclusions: Cutaneous, acral and mucosal NF1-mutated melanomas vary in clinical and genetic characteristics and demonstrate a favourable outcome on immune checkpoint inhibition therapy.

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Characterization of risk factors and efficacy of medical management of immune-related hepatotoxicity in real-world patients with metastatic melanoma treated with immune checkpoint inhibitors

Cited by 30 publications

References 25 publications

Immune-Related Adverse Events Predict the Efficacy of Immune Checkpoint Inhibitors in Lung Cancer Patients: A Meta-Analysis

Immune-Related Adverse Events Predict the Efficacy of Immune Checkpoint Inhibitors in Lung Cancer Patients: A Meta-Analysis

The Danish metastatic melanoma database (DAMMED): A nation-wide platform for quality assurance and research in real-world data on medical therapy in Danish melanoma patients

NF1-mutated melanomas reveal distinct clinical characteristics depending on tumour origin and respond favourably to immune checkpoint inhibitors

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