Non-infectious cholecystopathy secondary to high-dose IL-2 cancer immunotherapy

Kuppler, Kevin; Jeong, Daniel; Choi, Jung Woo

doi:10.1177/2058460115579458

Cited by 2 publications

(1 citation statement)

References 8 publications

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“…Additionally, the production of pro-inflammatory cytokines such as interleukin-2 has been shown to be increased in dogs with IMHA compared to healthy control dogs (Swann et al 2016). In humans, gall bladder wall thickening secondary to interleukin-2 immunotherapy has been reported (Powell et al 1994, Premkumar et al 1998, Kuppler et al 2015. The cholecystopathy is rapidly reversible with discontinuation of interleukin-2 therapy.…”

Section: Discussionmentioning

confidence: 99%

Investigation of the association between gall bladder wall thickness and hypoalbuminaemia in dogs

Sparago

Rademacher

Dehghanpir

et al. 2021

J of Small Animal Practice

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To assess the correlation between gallbladder wall thickness and serum/plasma albumin concentrations in dogs.Materials and MethOds: Retrospective searches of digital medical record databases were conducted to identify dogs that had either severely low serum/plasma albumin concentration (<1.5 g/dL) or ultrasonographic evidence of gallbladder wall thickening (>2 mm). Analysis of covariance models were used to analyze gallbladder wall thickness with sample type (serum vs plasma), age, etiology, albumin, and albumin ´ etiology as the covariates.results: A total of 216 dogs met inclusion criteria. One-hundred and forty-six dogs had a thickened gallbladder wall (Group 1). Median serum/plasma albumin concentration for dogs in this group was 2.2 g/dL (1 to 5 g/dL), and 84 dogs (57.5%) had hypoalbuminemia (<2.5 g/dL). The search for dogs with severe hypoalbuminemia (< 1.5 g/dL) identified 70 dogs (Group 2). In this group, median gallbladder wall thickness was 1.3 mm (0.2 to 6.1 mm) and 17 dogs (24.3%) had a thickened gallbladder wall. Serum/plasma albumin concentration and gallbladder wall thickness were not significantly correlated for Group 1 (r = 0.0044, p = 0.9580) or Group 2 (r = -0.1137, p = 0.3487).A moderate negative correlation (-0.64) was identified between gallbladder wall thickness and albumin concentration in dogs with immune-mediated diseases (p = 0.03). clinical significance: Gallbladder wall thickness and serum/plasma albumin concentration are independent variables in dogs.

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Section: Discussionmentioning

confidence: 99%

Investigation of the association between gall bladder wall thickness and hypoalbuminaemia in dogs

Sparago

Rademacher

Dehghanpir

et al. 2021

J of Small Animal Practice

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High-dose interleukin-2 therapy related adverse events and implications on imaging

Shah

Declouette

Ansari-Gilani

et al. 2021

Diagn Interv Radiol

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High-dose interleukin-2 (HDIL-2) was initially approved for the treatment of metastatic renal cell carcinoma (mRCC) and metastatic melanoma in 1992 and 1998, respectively. IL-2 was discovered as a cytokine, known as T cell growth factor. The majority of IL-2 is produced by CD4+ T cells, CD8+ T cells, natural killer (NK) cells, and activated dendritic cells. IL-2 has numerous functions which include differentiation of CD4+ T cells, promoting CD8+ T cell cytotoxicity, and promoting NK cell cytotoxicity (1). When given intravenously at high doses, IL-2 therapy gained success in a subset of patients with metastatic melanoma or mRCC who achieved complete and durable responses (1). However, the high toxicity profile of HDIL-2 restricted this therapy to a minority of patients in highly specialized centers.Currently HDIL-2 has been relegated to a limited role in systemic therapy of mRCC and metastatic melanoma patients. Based on National Comprehensive Cancer Network (NCCN) guidelines, HDIL-2 has been useful for patients with favorable, intermediate, and poor risk clear cell mRCC patients who have excellent performance and normal organ function (2). Additionally, HDIL-2 is recommended as a second line regimen for metastatic or unresectable melanoma. HDIL-2 is contraindicated in patients with inadequate organ reserve, poor performance status, or with untreated/active brain metastases (3).Although HDIL-2 was more commonly used in 1990s, with the innovation in immune checkpoint inhibitors (ICIs), there has been a reemergence of HDIL-2 treatment as a combination therapy. The leading theory with including ICIs is the fact that these agents work downstream during the effector phase in a tumor. With IL-2 secretion activating tumor-specific T cells, HDIL-2 therapy could potentially work synergistically with ICIs (4). One study found that there was durable antitumor activity in metastatic melanoma and mRCC patients with HDIL-2 therapy after the patient had received programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor compared to patients who had just received IL-2. Thus, HDIL-2 remains an option for patients who have progressed on ICIs (5). With additional data, combination therapy may be the new norm for metastatic melanoma and mRCC treatment.New innovations to make HDIL-2 therapy safer has also surfaced with the creation of IL-2 conjugated with 6 releasable polyethylene glycol (PEG) chains (4). The mechanism behind PEGylated IL-2 revolves around the idea that the drug selectively binds to the IL-2Rabg isoform which preferentially activates effector T cells, which limits the side effect profile. Unfortu-ABSTRACT High-dose interleukin-2 (HDIL-2) therapy was initially approved by the U.S. Food and Drug Administration for metastatic renal cell carcinoma (mRCC) and metastatic melanoma. IL-2 is able to promote CD8+ T cell and natural killer (NK) cell cytotoxicity to increase tumoricidal activity of the innate immune system. HDIL-2 therapy is associated with a wide spectrum of immune-related adverse events (irAEs) t...

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Non-infectious cholecystopathy secondary to high-dose IL-2 cancer immunotherapy

Cited by 2 publications

References 8 publications

Investigation of the association between gall bladder wall thickness and hypoalbuminaemia in dogs

Investigation of the association between gall bladder wall thickness and hypoalbuminaemia in dogs

High-dose interleukin-2 therapy related adverse events and implications on imaging

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