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Published on: December 17, 2019
CD19 CAR-T cell therapy in a pediatric patient with MDA5+ dermatomyositis and rapidly progressive interstitial lung
Andrés París-Muñoz1, Rosa M Alcobendas-Rueda2, Cristina Verdú-Sánchez3
1CIBERER-ISCIII, IdiPAZ-CNIO Translational Research Unit in Pediatric Hemato-Oncology, La Paz University Hospital Research Institute, Spanish National Cancer Center, 28029 Madrid, Spain.
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.
Insights
CD19 CAR-T cell therapy offers a promising new treatment for severe Anti-melanoma differentiation-associated protein 5 dermatomyositis with rapidly progressive interstitial lung disease. A pediatric patient achieved long-term remission and became immunosuppressant-free.
Area of Science:
- Immunology
- Cell Therapy
- Rheumatology
Background:
- Anti-melanoma differentiation-associated protein 5 dermatomyositis (MDA5+DM) is a severe, potentially fatal autoimmune disease.
- Rapidly progressive interstitial lung disease (RPILD) is the primary cause of mortality in MDA5+DM patients.
- Existing treatments for MDA5+DM-RPILD are limited, presenting a significant clinical challenge.
Purpose of the Study:
- To evaluate the efficacy and safety of CD19 chimeric antigen receptor (CAR)-T cell therapy in a pediatric patient with severe MDA5+DM-RPILD.
- To assess the potential of CAR-T cell therapy as a treatment for refractory autoimmune diseases.
Main Methods:
- The study involved the first use of a second-generation CD19 CAR-T cell therapy (ARI-0001) in a pediatric case.
- Conventional treatments were administered to stabilize the patient before CAR-T cell therapy.
- Patient monitoring included assessment of B cell aplasia, CAR-T cell expansion, and clinical outcomes.
Main Results:
- The patient experienced stabilization of MDA5+DM-RPILD prior to CAR-T cell infusion.
- CAR-T cell expansion was observed, suggesting targeting of CD19+ B lymphocytes.
- No adverse events such as fever or cytokine release syndrome were noted.
- The patient showed gradual B cell reconstitution and significant improvements in cutaneous, motor, respiratory, and neurological functions.
- These improvements were sustained in an immunosuppressant-free state.
Conclusions:
- Compassionate use of CD19 CAR-T cell therapy (ARI-0001) led to long-term improvement in a pediatric patient with aggressive MDA5+DM-RPILD.
- The patient achieved an 11-month immunosuppressant-free remission, demonstrating the therapeutic potential of CAR-T cell therapy for refractory autoimmune conditions.
