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Defibrotide for the prevention and treatment of cytokine release syndrome and neurotoxicity associated with immunodepletion

A technology of neurotoxicity and cytokines, applied in receptors/cell surface antigens/cell surface determinants, nervous system diseases, immunoglobulin superfamily, etc.

Pending Publication Date: 2021-01-15
JAZZ PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, while these therapies show promise, treatment with CAR-T cells or bispecific antibodies can lead to massive and rapid release of cytokines into the blood and cause cytokine release syndrome (CRS) or CAR-T cell-associated Encephalopathy syndrome (CRES) [herein also referred to as CAR-T-associated neurotoxicity or ICANS (immune effector cell (IEC) therapy-associated neurotoxicity syndrome)]

Method used

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  • Defibrotide for the prevention and treatment of cytokine release syndrome and neurotoxicity associated with immunodepletion
  • Defibrotide for the prevention and treatment of cytokine release syndrome and neurotoxicity associated with immunodepletion
  • Defibrotide for the prevention and treatment of cytokine release syndrome and neurotoxicity associated with immunodepletion

Examples

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Embodiment 1

[0169] Example 1 - Defibrotide Prevents Chimeric Antigen Receptor (CAR)-T Cell-Associated Neurotoxicity and / or Development of CRS

[0170] The overall goal of management is to maximize the benefits of CAR-T therapy while minimizing the risk of life-threatening complications. Although numerous reports indicate that CRS and CRES (or CAR-T-associated neurotoxicity / ICANS) are mostly reversible, monitoring of these conditions requires high levels of medical care and prolonged hospitalization, and, although rare, is associated with mortality. Simultaneously accurate assessment and timely management of toxicity could mitigate adverse outcomes associated with these potentially curative immunotherapies, leading to the development of a safe and effective approach to preventing CRS and CRES (or CAR-T-associated neurotoxicity / ICANS), without affecting the curative effect.

[0171] CRS and CRES (or CAR-T-associated neurotoxicity / ICANS) are accompanied by endothelial activation and injury ...

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Abstract

The present disclosure provides method of preventing, lessening the effects, or treating cytokine release syndrome (CRS) or related disorders, and / or neurotoxicity associated with immunotherapy comprising administering defibrotide. The defibrotide can be administered after the immunotherapy begins or be administered prophylactically before immunotherapy begins or before the patient develops CRS and / or neurotoxicity.

Description

technical field [0001] The present disclosure relates to methods of administering defibrotide to prevent and / or treat cytokine release syndrome (CRS) and / or neurotoxicity associated, inter alia, with CAR-T or bispecific antibody therapy. Background technique [0002] Immunotherapy, including the use of lymphocyte depletion or monoclonal antibodies, has become an important tool in cancer and tumor treatment. T cells expressing chimeric antigens (CAR-T cells) and bispecific antibodies are becoming options for lymphocyte depletion. However, while these therapies show promise, treatment with CAR-T cells or bispecific antibodies can lead to massive and rapid release of cytokines into the blood and cause cytokine release syndrome (CRS) or CAR-T cell-associated Encephalopathy syndrome (CRES) [also referred to herein as CAR-T-associated neurotoxicity or ICANS (immune effector cell (IEC) therapy-associated neurotoxicity syndrome)]. [0003] CRS is characterized by high fever, hypot...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/711A61P25/00
CPCA61K31/711A61K45/06A61P25/00G01N33/574G01N2800/52C07K2319/03C07K14/7051A61K39/0011A61K2039/5156A61K2039/5158A61K9/0019A61K47/183A61K47/12G01N33/6896
Inventor S.麦克马洪Y.尾木
Owner JAZZ PHARMA
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