Hepatic Injury Induced by a Single Dose of Nivolumab – a Case Report and Literature Review

Kopecký, J; Kubeček, Ondřej; Geryk, Tomáš; Podhola, Miroslav; Žiaran, Miroslav; Priester, Peter; Hanisova, M; Borilova, Simona

doi:10.14735/amko2019133

Cited by 17 publications

(10 citation statements)

References 13 publications

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“…Our meta-analysis showed that, compared with standard chemotherapy, PD-1/PD-L1 inhibitor monotherapy and PD-1/PD-L1 inhibitor plus chemotherapy significantly increased the risk of all-grade and high-grade hepatitis. We found no descriptions of hepatitis in any of the trials that examined nivolumab, but some case reports indicated immune-related hepatitis after nivolumab treatment [35,40].…”

Section: Discussionmentioning

confidence: 86%

“…Corticosteroid therapy is the mainstay of irAE management, although the response of immune-related liver injury to corticosteroid therapy can be variable. Kopecky et al [40] demonstrated a poor response to corticosteroid therapy when cholestatic hepatitis occurred in immune-mediated liver injury, and suggested use of a more potent immunosuppressive treatment.…”

Section: Discussionmentioning

confidence: 99%

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Hepatotoxicity in patients with solid tumors treated with PD-1/PD-L1 inhibitors alone, PD-1/PD-L1 inhibitors plus chemotherapy, or chemotherapy alone: systematic review and meta-analysis

Guo

et al. 2020

Eur J Clin Pharmacol

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Background This meta-analysis examined the risk of hepatotoxicity in patients with solid tumors who received a PD-1/PD-L1 inhibitor alone, a PD-1/PD-L1 inhibitor plus chemotherapy, or chemotherapy alone. Methods Potentially eligible studies were identified by searches of Embase and PubMed. All included studies were randomized controlled trials (RCTs) that examined patients with solid tumors who received a PD-1/PD-L1 inhibitor and/or chemotherapy. Results We included 20 clinical trials (11,634 patients). Thirteen trials compared PD-1/PD-L1 inhibitor monotherapy with chemotherapy. These two groups had similar risk for elevated markers of hepatotoxicity (based on analysis of all marker grades and high marker grades), although the PD-1/PD-L1 inhibitor group had an elevated relative risk (RR) of elevated aspartate aminotransferase (AST; RR = 2.13, 95% CI = 1.04 to 4.36, P = 0.04) when considering high grades alone; however, this disparity was not significant for comparisons of the pembrolizumab and nivolumab subgroups with the chemotherapy group. Compared with chemotherapy, PD-1/PD-L1 inhibitors increased the risk of all-grade hepatitis (RR = 5.85, 95% CI = 1.85 to 18.46, P < 0.01), and high-grade hepatitis (RR = 5.66, 95% CI = 1.58 to 20.27, P < 0.01). Seven other studies compared PD-1/PD-L1 inhibitor plus chemotherapy with chemotherapy alone. The combined treatment led to a higher risk for all-grade hepatitis (RR = 2.14, 95% CI = 1.29 to 3.55, P < 0.01) and high-grade hepatitis (RR = 5.24, 95%CI = 1.89 to 14.52, P < 0.01), but these groups had similar risk for all-grade and high-grade elevated markers of hepatotoxicity. Conclusions Relative to chemotherapy alone, PD-1/PD-L1 inhibitors with or without chemotherapy increased the risk of all-grade and high-grade hepatitis, but generally did not increase the risk of elevated blood markers of hepatotoxicity.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Hepatotoxicity in patients with solid tumors treated with PD-1/PD-L1 inhibitors alone, PD-1/PD-L1 inhibitors plus chemotherapy, or chemotherapy alone: systematic review and meta-analysis

Guo

et al. 2020

Eur J Clin Pharmacol

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“…In these cases, a second immunosuppressive drug can be added, the most widely used being mycophenolate mofetil (MMF). 66,74,105,107,108,110,111 Azathioprine has also been used with success. 68,106 In a few clinical observations, the use of calcineurin inhibitors (cyclosporine and tacrolimus) has also been described as effective.…”

Section: Patients With Hepatitis Refractory To Corticosteroidsmentioning

confidence: 99%

Liver toxicity as a limiting factor to the increasing use of immune checkpoint inhibitors

et al. 2020

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Immune checkpoint inhibitors (ICIs) improve clinical outcomes in patients suffering from different types of cancer. Liver toxicity is one of the immune-related adverse events associated with immunotherapy; although not common, its management is challenging as it is extremely heterogeneous in terms of presentation and severity. Differences in the development and evolution of ICI-related toxicity in healthy or cirrhotic livers have not yet been elucidated. Assessing causality is key to diagnosing ICI-induced liver toxicity; liver biopsies can assist not only in the differential diagnosis but also in assessing the severity of histological liver damage. The current classification of severity overestimates the grade of liver injury and needs to be revised to reflect the views of hepatologists. Spontaneous improvements in ICI-related liver toxicity have been reported, so corticosteroid therapy should probably be individualised not systematic. The reintroduction of ICIs in a patient with previous immune-mediated hepatitis may be possible, but the risk/benefit ratio should be considered, as the risk factors for hepatitis recurrence are currently unclear. The management of these patients, requiring a balance between efficacy, toxicity and specific treatments, necessitates multidisciplinary collaboration. The incidence of immune-related liver toxicity will continue to rise based on the increasing use of ICIs for most cancers, mandating improved understanding and management of this complication.

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“…Low-risk HPV types include types 6, 11, 42, 43, and 44. High-risk HPV types include types 16,18,31,33,34,35,39,45,51,52,56,58,59,66,68, and 70 [25,26]. Vaccines against HPV are essential to prevent the development of CC and other gynecologic cancers and to protect against HPV types 16 and 18.…”

Section: Risk Factors and Clinical Featuresmentioning

confidence: 99%

“…Currently, several clinical trials are assessing the clinical activity and safety of PD-L1 inhibitor monotherapy or in combination with chemotherapeutic agents such as bevacizumab, paclitaxel or carboplatin, cobimetinib (the mitogen-activated protein kinase enzymes inhibitor) [65], and platinum-based chemotherapy in OC (Table 4) [66,67]. The KGOG 3045 study aims to investigate durvalumab therapy in platinum-resistant recurrent OC patients [65,68]. In total, 68 patients have been randomized into four groups: group 1 will receive olaparib and cediranib, group 2 will receive olaparib and durvalumab, group 3 will receive durvalumab plus chemotherapy, and group 4 will receive durvalumab and tremelimumab plus chemotherapy.…”

Section: Monotherapy or Combination Therapy With Pd-l1 Inhibitors In mentioning

confidence: 99%

The Latest Findings of PD-1/PD-L1 Inhibitor Application in Gynecologic Cancers

Kooshkaki

Derakhshani

Safarpour

et al. 2020

IJMS

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Gynecologic cancers account for approximately 11% of the newly diagnosed cancers in women in the United States and for 18% globally. The presence of tumor-infiltrating lymphocytes (TILs) influences the clinical outcome of cancer patients and immune checkpoint inhibitors (ICIs), including anti programmed cell death protein-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), and anticytotoxic T-lymphocyte antigen 4 (anti-CTLA-4), which have been approved for treating different types of malignancies. Antibodies targeting the PD-1/PD-L1 checkpoint have shown dynamic and durable tumor regressions, suggesting a rebalancing of the host–tumor interaction. There are several the US food and drug administration (FDA)-approved ICIs targeting PD-1, including pembrolizumab and nivolumab, as well as those targeting PD-L1, including avelumab, atezolizumab, and durvalumab for melanoma, renal cell cancer, colorectal cancer, head and neck cancer, cervix cancer, urothelial cancer, and lung cancer. Current pre-clinical and clinical studies assessing PD-1/PD-L1 inhibitors in several gynecologic cancers have reported significant antitumor activity. In this review, we investigate pre-clinical and clinical studies that describe the safety and efficacy of anti-PD-1/PD-L1 antibodies, with a particular focus on ongoing clinical trials, analyzing the oncological outcome and adverse effects of ICIs in gynecologic cancers.

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Hepatic Injury Induced by a Single Dose of Nivolumab – a Case Report and Literature Review

Cited by 17 publications

References 13 publications

Hepatotoxicity in patients with solid tumors treated with PD-1/PD-L1 inhibitors alone, PD-1/PD-L1 inhibitors plus chemotherapy, or chemotherapy alone: systematic review and meta-analysis

Hepatotoxicity in patients with solid tumors treated with PD-1/PD-L1 inhibitors alone, PD-1/PD-L1 inhibitors plus chemotherapy, or chemotherapy alone: systematic review and meta-analysis

Liver toxicity as a limiting factor to the increasing use of immune checkpoint inhibitors

The Latest Findings of PD-1/PD-L1 Inhibitor Application in Gynecologic Cancers

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