Kidney injuries related to ipilimumab

Izzedine, Hassane; Gueutin, Victor; Gharbi, Chems; Mateus, Christine; Robert, Caroline; Routier, Émilie; Thomas, Marina; Baumelou, A; Rouvier, Philippe

doi:10.1007/s10637-014-0092-7

Cited by 155 publications

(119 citation statements)

References 19 publications

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“…irAEs can affect any organ system, but typically include the skin, the gastrointestinal (GI) tract, and the hepatic, endocrine and respiratory systems [35]. Other rare events such as uveitis, pancreatitis, hematological events, neurologic adverse events, and nephritis have also been reported [36,37,38,39,40]. In general, irAEs are manageable by the use of immunosuppressive therapy (e.g.…”

Section: Managing Toxicity and Side-effects Of Pd-1- And Pd-l1-directmentioning

confidence: 99%

PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer

et al. 2016

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Immune checkpoint inhibition represents a major recent breakthrough in the treatment of malignant diseases including breast cancer. Blocking the programmed death receptor-1 (PD-1) and its ligand, PD-L1, has shown impressive antitumor activity and may lead to durable long-term disease control, especially in the triple-negative subtypes of breast cancer (TNBC). Although immune checkpoint blockade is generally well tolerated, specific immune-related adverse events (irAEs) may occur. This review summarizes the clinical efficacy, perspectives, and future challenges of using PD-1/PD-L1-directed antibodies in the treatment of breast cancer.

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Section: Managing Toxicity and Side-effects Of Pd-1- And Pd-l1-directmentioning

confidence: 99%

PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer

et al. 2016

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“…Cell-mediated immune response leading to inflammatory cell infiltrates with and without granulomas has been reported [15,16]. Cases of acute interstitial nephritis (AIN) in the initial trials, arising 2-12 weeks post drug administration have been reported and one of them demonstrated granulomas [12,17,18,19,20,21,22]. The largest series of biopsy-proven cases of AKI was reported by Cortazar et al [12].…”

Section: Introductionmentioning

confidence: 99%

Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review

Wanchoo

Karam²,

Uppal³

et al. 2017

Am J Nephrol

11,142

256

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Background: Cancer immunotherapy, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death 1 (PD-1), has revolutionized the treatment of malignancies by engaging the patient's own immune system against the tumor rather than targeting the cancer directly. These therapies have demonstrated a significant benefit in the treatment of melanomas and other cancers. Summary: In order to provide an extensive overview of the renal toxicities induced by these agents, a Medline search was conducted of published literature related to ipilimumab-, pembrolizumab-, and nivolumab-induced kidney toxicity. In addition, primary data from the initial clinical trials of these agents and the FDA adverse reporting system database were also reviewed to determine renal adverse events. Acute interstitial nephritis (AIN), podocytopathy, and hyponatremia were toxicities caused by ipilimumab. The main adverse effect associated with both the PD-1 inhibitors was AIN. The onset of kidney injury seen with PD-1 inhibitors is usually late (3-10 months) compared to CTLA-4 antagonists related renal injury, which happens earlier (2-3 months). PD-1 as opposed to CTLA-4 inhibitors has been associated with kidney rejection in transplantation. Steroids appear to be effective in treating the immune-related adverse effects noted with these agents. Key Message: Although initially thought to be rare, the incidence rates of renal toxicities might be higher (9.9-29%) as identified by recent studies. As a result, obtaining knowledge about renal toxicities of immune checkpoint inhibitors is extremely important.

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“…Other rare irAEs related to checkpoint blockade include episcleritis, conjunctivitis, uveitis (51), neurologic adverse effects (52), increase of amylase and lipase, diabetes, pancreatitis (21,41), hematologic adverse effects (i.e., cytopenia, red cell aplasia, autoimmune neutropenia, acquired haemophilia A) (36,53,54), nephritis, glomerular lupus-like nephropathy and renal dysfunction (<1%, presenting after 10 months) (41,55) and pneumonitis. Pneumonitis is notable, because rare treatment-related deaths have been experienced in early clinical studies of PD-1 blockade (4).…”

Section: Delayed Treatment Effectmentioning

confidence: 99%

The European Organization for Research and Treatment of Cancer perspective on designing clinical trials with immune therapeutics

et al. 2016

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Cancer immunotherapy has had a major impact on the established paradigms of drug development and clinical trial research. The innovative mechanism of action of these compounds has resulted in new patterns of response and safety profiles, which pose challenges for the classical trial methodology. In this review we report on the search for the maximum tolerated dose, the recommended phase II dose and the appropriate target population in phase I trials. We provide some statistical considerations on the choice of endpoints for phase II and III trials and the limitations of frequently used trial designs in the presence of a delayed treatment effect, which may be induced by the immune modulating effect of the checkpoint inhibitors. We summarize the currently available data on the safety profile of these new compounds, which can guide protocol safety recommendations. Finally, we report on the current evidence of biomarker development.

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Kidney injuries related to ipilimumab

Cited by 155 publications

References 19 publications

PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer

PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer

Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review

The European Organization for Research and Treatment of Cancer perspective on designing clinical trials with immune therapeutics

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