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

Abstract

Background: 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.

Methods: 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.

Findings: 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).

Conclusions: 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).

Funding: 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.

Keywords: CAR-T cell; MDA5+; RPILD; Translation to patients; autoimmunity; cell immunotherapy; dermatomyositis; pediatric rheumatology.