CD19 CAR-T therapy yields long-term benefits in lupus, myositis, systemic sclerosis
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WASHINGTON — CD19 chimeric antigen receptor T-cell therapy led to remission, or ceased disease progression, over a period of up to 15 months in 35 patients with lupus, myositis and systemic sclerosis, according to data.
“In March 2021, Georg Schett, MD, and Andreas Mackensen, MD, were brave enough in the middle of the pandemic to treat ... the first lupus patient treated with CD19 CAR T, and the results were very impressive,” Melanie Hagen, MD, of the University of Erlangen-Nuremberg, in Germany, told attendees at ACR Convergence 2024. “Afterward, we could see consistent results with the next patients.”
To assess the performance of this newly emerging treatment over a longer timeline, Hagen and colleagues tracked the status of 35 patients who received autologous CD19 CAR T-cell therapy between 2021 and 2024, either under a compassionate use program or the phase 1 CASTLE study. Tracked participants had refractory, progressive systemic lupus erythematosus (n = 19), SSc (n = 11) or idiopathic inflammatory myositis (IIM) (n = 5), and were observed for a median follow-up period of 15 months, with 28 reaching the 6-month follow-up mark.
The patients received fludarabine and cyclophosphamide lymphodepletion prior to therapy, and all immunosuppressives were stopped 2 weeks prior.
Overall, the treatments brought long-term remission or halted disease progression, with minimal disease recurrence, according to the researchers. At 6 months and beyond, “the vast majority” of patients with SLE demonstrated a SLEDAI score of zero and fulfilled DORIS remission criteria, while one had “minimal stable disease activity,” Hagen said.
For IIM, muscle weakness — measured via the MMT8 score — improved over long-term follow-up, although one patient flared.
In SSc, modified Rodnan skin scores showed “significant improvement” across the follow-up timeframe, Hagen said.
According to the researchers, the sole relapse was of mild myositis in a patient with IIM who had been in drug-free remission for 15 months.
Regarding safety, the researchers stated that tolerability was high with no higher-grade toxicities. Approximately 60% of patients experienced grade 1 cytokine release syndrome, while three participants demonstrated grade 2. The most common adverse effect of CAR-T therapy, immune-cell associated hematotoxicity, occurred in 80% of patients within 30 days.
“We performed two bone marrow biopsies, and it’s very important that we haven’t seen blasts or dysplasia,” Hagen said. “It’s important that the hematotoxicity responds well to granulocyte-colony stimulating factor treatment, if needed, or recovers without treatment.”
In addition, seven patients had infections requiring hospitalization, mainly pneumonia, and there was one reactivation of cytomegalovirus, according to Hagen.
“After 35 patients, I think it’s absolutely clear that CD19 CAR T-cell is a safe and efficient approach,” she said. “Low-grade CRS and hepatotoxicity are the most common adverse events, which are very well manageable, and CD19 CAR-T cells can prevent from ongoing immunosuppressants.”
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Hagen M. Abstract #1749. Presented at: ACR Convergence 2024; Nov. 14-19, 2024; Washington, D.C.
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