CD19 CAR-T cell therapy in a pediatric patient with MDA5+ dermatomyositis and rapidly progressive interstitial lung disease

• Published in: Med (New York, N.Y. : Online) Vol. 6; no. 8; p. 100676
• Main Authors: París-Muñoz, Andrés, Alcobendas-Rueda, Rosa M., Verdú-Sánchez, Cristina, Udaondo, Clara, Galán-Gómez, Víctor, González-Martínez, Berta, Menéndez, Juan J., Martínez-Romera, Isabel, Minguillón, Jordi, Pertíñez, Lidia, de Manuel-Gómez, Cristina, de la Cruz-Benito, Ana, Sanz-Rupérez, Alejandro, Remesal, Agustín, Cámara, Carmen, Sánchez-Zapardiel, Elena, del Pino-Molina, Lucía, Gómez-Zamora, Ana, Serrano-Olmedo, María G., Español-Rego, Marta, Ruiz de Valbuena, Marta, Climent, Francisco, Dorao, Paloma, Ríos-Blanco, Juan J., Andrade, José D., Ruiz-Zurita, Gonzalo, Fernández-García, Miguel A., Pérez-Martínez, Antonio
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.08.2025
• Subjects: Antigens, CD19 - immunology; autoimmunity; CAR-T cell; cell immunotherapy; Child; dermatomyositis; Dermatomyositis - complications; Dermatomyositis - immunology; Dermatomyositis - therapy; Disease Progression; Humans; Immunotherapy, Adoptive - methods; Interferon-Induced Helicase, IFIH1 - immunology; Lung Diseases, Interstitial - immunology; Lung Diseases, Interstitial - therapy; MDA5; pediatric rheumatology; Receptors, Chimeric Antigen; RPILD; cell immunotherapy; autoimmunity; pediatric rheumatology; dermatomyositis; RPILD; Translation to patients; CAR-T cell; MDA5
• ISSN: 2666-6340; 2666-6340
• DOI: 10.1016/j.medj.2025.100676

Anti-melanoma differentiation-associated protein 5 dermatomyositis (MDA5+DM) is a potentially fatal subtype of dermatomyositis. The most severe cases are characterized by rapidly progressive interstitial lung disease (RPILD), the leading cause of death in these patients. There is currently no curative treatment for these patients, and indeed, MDA5+DM-RPILD is considered one of the most challenging pathologies in medicine. Nevertheless, the recent introduction of CD19 chimeric antigen receptor (CAR)-T cell therapies appears to offer a serious opportunity to develop solutions for complex autoimmune diseases refractory to multiple immunosuppressant treatments, mainly rheumatic diseases such as rheumatoid arthritis, dermatomyositis, and systemic lupus erythematosus. In this report, we describe the first use of a second-generation CD19 CAR-T cell therapy (ARI-0001) in a pediatric patient with severe MDA5+DM-RPILD. Conventional treatments stabilized MDA5+DM-RPILD before CAR-T cell inoculation (−34 days). The presence of CD19+ B lymphocytes that might serve as target cells in deeper tissues was suspected due to CAR-T cell expansion in a context of B cell aplasia. No fever or cytokine release syndrome/cell-associated neurotoxicity syndrome was evident. In global terms, B cell reconstitution and cutaneous, motor, respiratory, and neurological improvements were observed gradually in the patient in an immunosuppressant-free context (−7 to +325 days). A pediatric patient with aggressive MDA5+DM-RPILD achieved progressive long-term improvement and immunosuppressant-free remission over 11 months after compassionate use of a CD19 CAR-T cell therapy (ARI-0001). This work was supported by the Programa Investigo (PI_SEPE_APM) and grants from the ISC-III (PI22/01226) from the Comunidad de Madrid (S2022/BMD-7225) and from the CRIS Cancer Foundation. [Display omitted] •CD19 CAR-T cell therapy showed efficacy and safety in a pediatric case of MDA5+DM-RPILD•CAR+ T cell expansion indicates that other non-peripheral B cells acted as CD19+ targets•Lung function improved in an immunosuppressant-free context for 11 months•B cell compartment reconstitution occurred in absence of new autoimmune episodes MDA5+ dermatomyositis with interstitial lung disease (MDA5+DM-RPILD) is a rare autoimmune disease that lacks a well-defined treatment. Because B cells are key players in autoimmunity, CD19 CAR-T cell therapies have been proposed as a strategy to deeply deplete this cell population. In this report, researchers from Hospital Universitario La Paz describe the use of CD19 CAR-T cell therapy in a pediatric patient with MDA5+DM-RPILD after a complex immunosuppressive regimen. For 11 months in an immunosuppressant-free context, the subject progressively exhibited motor and lung improvements and restoration of the B cell compartment in the absence of autoimmune episodes. This work joins the list of autoimmune cases successfully treated with CAR-T cell therapies and demonstrates their efficacy and safety even in dire clinical conditions. Researchers and clinicians from Hospital Universitario La Paz report the use of CD19 CAR-T cell therapy in a pediatric case of MDA5+ dermatomyositis with interstitial lung disease, one of the most challenging autoimmune diseases in medicine. B cell compartment restoration and lung improvement were observed during 11 months without immunosuppressants.