Emapalumab for the treatment of hemophagocytic lymphohistiocytosis

Cheloff, Abraham Z.; Al‐Samkari, Hanny

doi:10.1358/dot.2020.56.7.3145359

Cited by 13 publications

(11 citation statements)

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“…So far, there are no descriptions of such clinical cases; thus the aim of this case report is to draw attention to the need to search for new therapeutic options for these patients. Recently, monoclonal antibodies (such as emapalumab, a human IgG1 monoclonal antibody against interferon-gamma) and JAK pathway inhibitors (such as ruxolitinib) have been approved and reported to be effective in the treatment of HLH [65][66][67][68][69]. Further clinical trials are ongoing to confirm the effectiveness and safety of these and other biological and small molecule therapies in different groups of patients suffering from HLH.…”

Section: Peculiarities Of Current Casementioning

confidence: 99%

Multifocal Pyoderma Gangrenosum with an Underlying Hemophagocytic Lymphohistiocytosis: Case Report and the Review of the Literature

Opalińska

Kwiatkowska

Burdacki

et al. 2021

Dermatol Ther (Heidelb)

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Pyoderma gangrenosum (PG) is an uncommon, serious, ulcerating skin disease of uncertain etiology. It manifests as a noninfectious, progressive necrosis of the skin characterized by sterile neutrophilic infiltrates. It seems to be a disorder of the immune system. PG is associated with certain underlying conditions in at least 50% of cases. Therefore, it is important to look carefully for comorbidities in every patient with PG and treat them adequately to improve the prognosis. Here, we demonstrate a 35-year-old man diagnosed with multifocal PG and hemophagocytic lymphohistiocytosis (HLH) with fatal outcome, despite combined, longterm, intensive dermatological and hematological treatment with high doses of steroids, cyclosporin, intravenous immunoglobulins (IVIG), HLH-2004 protocol with intravenously administered etoposide, and anakinra. This case is presented owing to the extremely rare coexistence of PG and HLH and the related diagnostic and therapeutic difficulties. It is also worth underlying that the diagnosis of HLH should perhaps be considered in the presence of a high percentage of double-negative T lymphocytes (DNTs) in flow cytometry, after excluding the diagnosis of lymphoma and leukemia. In this article we have also performed and present the critical literature review of local and systemic options in the management of PG lesions based on a detailed search of the PubMed database.

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Section: Peculiarities Of Current Casementioning

confidence: 99%

Multifocal Pyoderma Gangrenosum with an Underlying Hemophagocytic Lymphohistiocytosis: Case Report and the Review of the Literature

Opalińska

Kwiatkowska

Burdacki

et al. 2021

Dermatol Ther (Heidelb)

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“…More recently, a deeper understanding of the molecular basis of HLH has led to the discovery of newer biological therapies for HLH. The central role of interferon-gamma (IFN-γ) in hyperinflammation in HLH led to the development of emapalumab, a monoclonal antibody against IFN-γ ( 84 ). It was FDA approved in 2018 for relapsed, refractory, or progressive familial HLH ( 85 ).…”

Section: Treatmentmentioning

confidence: 99%

Traffic jam within lymphocytes: A clinician’s perspective

Vasanna

Dalal

2023

Front. Immunol.

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With the discovery of novel diseases and pathways, as well as a new outlook on certain existing diseases, cellular trafficking disorders attract a great deal of interest and focus. Understanding the function of genes and their products in protein and lipid synthesis, cargo sorting, packaging, and delivery has allowed us to appreciate the intricate pathophysiology of these biological processes at the molecular level and the multi-system disease manifestations of these disorders. This article focuses primarily on lymphocyte intracellular trafficking diseases from a clinician’s perspective. Familial hemophagocytic lymphohistiocytosis is the prototypical disease of abnormal vesicular transport in the lymphocytes. In this review, we highlight other mechanisms involved in cellular trafficking, including membrane contact sites, autophagy, and abnormalities of cytoskeletal structures affecting the immune cell function, based on a newer classification system, along with management aspects of these conditions.

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“…Obviously, we and others generated monoclonal antibodies to these cytokines and their receptors ( 9 ). Anti IFNγ mAbs developed by others translated to Emapalumab ® , a drug approved in 2018 for primary hemophagocytic lymphohistiocytosis (HLH) ( 25 ). In the current pandemic these blocking agents are being considered for the treatment of severe cases of COVID 19.…”

Section: The Discovery Of Cytokine Receptors and Binding Proteinsmentioning

confidence: 99%

A natural goldmine of binding proteins and soluble receptors simplified their translation to blockbuster drugs, all in one decade

Novick

2023

Front. Immunol.

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Human urinary proteins are a goldmine of natural proteins a feature that simplifies their translation to biologics. Combining this goldmine together with the ligand-affinity-chromatography (LAC) purification method, proved a winning formula in their isolation. LAC specificity, efficiency, simplicity and inherent indispensability in the search for predictable and unpredictable proteins, is superior to other separation techniques. Unlimited amounts of recombinant cytokines and monoclonal antibodies (mAb) accelerated the “triumph”. My approach concluded 35 years of worldwide pursuit for Type I IFN receptor (IFNAR2) and advanced the understanding of the signal transduction of this Type of IFN. TNF, IFNγ and IL-6 as baits enabled the isolation of their corresponding soluble receptors and N-terminal amino acid sequence of the isolated proteins facilitated the cloning of their cell surface counterparts. IL-18, IL-32, and heparanase as the baits yielded the corresponding unpredictable proteins: the antidote IL-18 Binding Protein (IL-18BP), the enzyme Proteinase 3 (PR3) and the hormone Resistin. IFNβ proved beneficial in Multiple Sclerosis and is a blockbuster drug, Rebif®. TNF mAbs translated into Remicade® to treat Crohn’s disease. Enbrel® based on TBPII is for Rheumatoid Arthritis. Both are blockbusters. Tadekinig alfa™, a recombinant IL-18BP, is in phase III clinical study for inflammatory and autoimmune diseases. Seven years of continuous compassionate use of Tadekinig alfa™ in children born with mutations (NLRC4, XIAP) proved life-saving and is an example of tailored made medicine. IL-18 is a checkpoint biomarker in cancer and IL-18BP is planned recently to target cytokine storms resulting from CAR-T treatment and in COVID 19.

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Emapalumab for the treatment of hemophagocytic lymphohistiocytosis

Cited by 13 publications

References 0 publications

Multifocal Pyoderma Gangrenosum with an Underlying Hemophagocytic Lymphohistiocytosis: Case Report and the Review of the Literature

Multifocal Pyoderma Gangrenosum with an Underlying Hemophagocytic Lymphohistiocytosis: Case Report and the Review of the Literature

Traffic jam within lymphocytes: A clinician’s perspective

A natural goldmine of binding proteins and soluble receptors simplified their translation to blockbuster drugs, all in one decade

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