CD19-targeted chimeric antigen receptor T cell therapy in two patients with multiple sclerosis

TY - JOUR

T1 - CD19-targeted chimeric antigen receptor T cell therapy in two patients with multiple sclerosis

AU - Fischbach, Felix

AU - Richter, Johanna

AU - Pfeffer, Lena Kristina

AU - Fehse, Boris

AU - Berger, Susanna Carolina

AU - Reinhardt, Stefanie

AU - Kuhle, Jens

AU - Badbaran, Anita

AU - Rathje, Kristin

AU - Gagelmann, Nico

AU - Borie, Dominic

AU - Seibel, Johan

AU - Ayuk, Francis

AU - Friese, Manuel A

AU - Heesen, Christoph

AU - Kröger, Nicolaus

N1 - Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2024/6/14

Y1 - 2024/6/14

N2 - BACKGROUND: Progressive multiple sclerosis (MS) is characterized by compartmentalized smoldering neuroinflammation caused by the proliferation of immune cells residing in the central nervous system (CNS), including B cells. Although inflammatory activity can be prevented by immunomodulatory therapies during early disease, such therapies typically fail to halt disease progression. CD19 chimeric antigen receptor (CAR)-T cell therapies have revolutionized the field of hematologic malignancies. Although generally considered efficacious, serious adverse events associated with CAR-T cell therapies such as immune effector cell-associated neurotoxicity syndrome (ICANS) have been observed. Successful use of CD19 CAR-T cells in rheumatic diseases like systemic lupus erythematosus and neuroimmunological diseases like myasthenia gravis have recently been observed, suggesting possible application in other autoimmune diseases.METHODS: Here, we report the first individual treatment with a fully human CD19 CAR-T cell therapy (KYV-101) in two patients with progressive MS.FINDINGS: CD19 CAR-T cell administration resulted in acceptable safety profiles for both patients. No ICANS was observed despite detection of CD19 CAR-T cells in the cerebrospinal fluid. In case 1, intrathecal antibody production in the cerebrospinal fluid decreased notably after CAR-T cell infusion and was sustained through day 64.CONCLUSIONS: CD19 CAR-T cell administration in progressive MS resulted in an acceptable safety profile. CAR-T cell presence and expansion were observed in the cerebrospinal fluid without clinical signs of neurotoxicity, which, along with intrathecal antibody reduction, indicates expansion-dependent effects of CAR-T cells on CD19+ target cells in the CNS. Larger clinical studies assessing CD19 CAR-T cells in MS are warranted.FUNDING: Both individual treatments as well the generated data were not based on external funding.

AB - BACKGROUND: Progressive multiple sclerosis (MS) is characterized by compartmentalized smoldering neuroinflammation caused by the proliferation of immune cells residing in the central nervous system (CNS), including B cells. Although inflammatory activity can be prevented by immunomodulatory therapies during early disease, such therapies typically fail to halt disease progression. CD19 chimeric antigen receptor (CAR)-T cell therapies have revolutionized the field of hematologic malignancies. Although generally considered efficacious, serious adverse events associated with CAR-T cell therapies such as immune effector cell-associated neurotoxicity syndrome (ICANS) have been observed. Successful use of CD19 CAR-T cells in rheumatic diseases like systemic lupus erythematosus and neuroimmunological diseases like myasthenia gravis have recently been observed, suggesting possible application in other autoimmune diseases.METHODS: Here, we report the first individual treatment with a fully human CD19 CAR-T cell therapy (KYV-101) in two patients with progressive MS.FINDINGS: CD19 CAR-T cell administration resulted in acceptable safety profiles for both patients. No ICANS was observed despite detection of CD19 CAR-T cells in the cerebrospinal fluid. In case 1, intrathecal antibody production in the cerebrospinal fluid decreased notably after CAR-T cell infusion and was sustained through day 64.CONCLUSIONS: CD19 CAR-T cell administration in progressive MS resulted in an acceptable safety profile. CAR-T cell presence and expansion were observed in the cerebrospinal fluid without clinical signs of neurotoxicity, which, along with intrathecal antibody reduction, indicates expansion-dependent effects of CAR-T cells on CD19+ target cells in the CNS. Larger clinical studies assessing CD19 CAR-T cells in MS are warranted.FUNDING: Both individual treatments as well the generated data were not based on external funding.

U2 - 10.1016/j.medj.2024.03.002

DO - 10.1016/j.medj.2024.03.002

M3 - Case report

C2 - 38554710

VL - 5

SP - 550-558.e2

JO - MED-CAMBRIDGE

JF - MED-CAMBRIDGE

SN - 2666-6340

IS - 6

ER -