MINNEAPOLIS — Chimeric antigen receptor (CAR) T-cell therapy in children with certain rheumatologic conditions appears to be safe and effective in inducing drug-free remission at least in the short-term, according to research presented at the American College of Rheumatology’s Pediatric Rheumatology Symposium (PRSYM) 2026.

CAR T-cell therapy is a form of immunotherapy that has been successfully used for years in oncology, but it has only recently been explored for potentially treating autoimmune and autoinflammatory conditions. It has shown significant promise in drug-free remission in adults with rheumatologic conditions in recent years, but evidence is more sparse in pediatric patients.

This technology is “new and exciting” but is also “relatively unchartered territory for pediatric rheumatology,” Randy Cron, MD, PhD, a professor of medicine and director of pediatric rheumatology at Heersink School of Medicine, The University of Alabama at Birmingham, told Medscape Medical News. “The possibility of a cure for our severe diseases, even if only anecdotal, is captivating,” he said, but the technology is also expensive and not available to all patients.

The research presented was a case series of eight pediatric patients, ranging in age from 3 to 16 years, who underwent CAR T-cell therapy for various rheumatologic conditions. Four patients had systemic lupus erythematosus (SLE), three had juvenile dermatomyositis (JDM), and one had juvenile systemic sclerosis. The first patient was treated starting in 2023.

“These data provide evidence of the short- and medium-term efficacy and safety of CD19 CAR T-cell therapy [zorpocabtagene autoleucel] in pediatric patients with refractory autoimmune disease,” Claudia Bracaglia, MD, a pediatric rheumatologist at IRCCS Ospedale Pediatrico Bambino Gesù in Rome, Italy, told attendees in presenting the findings. “This is a potentially curative option in patients with aggressive autoimmune disease,” she said, but prospective studies are necessary to validate these preliminary findings in larger patient cohorts.

All eight patients had previously received at least four and up to eight therapies. All had received glucocorticoids and mycophenolate mofetil, and other previous therapies among the patients included plasmapheresis, rituximab, cyclophosphamide, belimumab, azathioprine, cyclosporine A, hydroxychloroquine, intravenous immunoglobulin (IVIG), JAK inhibitors, adalimumab, methotrexate, and obinutuzumab.

The patients received lymphodepletion with cyclophosphamide and fludarabine during the 3-5 days leading up to the collection of T cells. The CD19 CAR T cells were produced using an automated fresh-to-fresh process in a Good Manufacturing Practice-certified academic cell factory and infused on day 12 after collection.

At the time of presentation, four of the six patients with follow-up from 6 months to 33 months had achieved drug-free remission while the other two were drug-free and showing improvement but not yet in remission. It was too early to determine efficacy for the two patients with SLE who had 7 weeks and 2 months follow-up.

All three patients with JDM, one of whom was still improving, achieved and maintained major clinical response based on the Total Improvement Score. The two patients with SLE in drug-free remission had normalization of their SLE Disease Activity Index-2K score at the third month, a score of 0 from a baseline of 22 for one and from a baseline of 38 for the other. The patient with juvenile systemic sclerosis was the one with 6 months of follow-up showing improvement, and they had maintained stable lung and cardiac involvement at their last follow-up.

Four patients — two with SLE and two with JDM — had grade 1 cytokine release syndrome (CRS), and one patient with JDM had a grade 1 case of immune effector cell-associated neurotoxicity syndrome (ICANS). All the patients experienced grade 2-3 transient anemia and grade 3-4 range neutropenia, but cytopenia was limited to the first few weeks after infusion. None of the patients experienced hypogammaglobulinemia requiring IVIG replacement, and no severe infections occurred.

Potential Sparing of a Lifetime of Illness, but a Long Horizon for Potential Recurrence

In a separate presentation at the meeting, Holly Wobma, MD, PhD, a pediatric rheumatologist and instructor at Boston Children’s Hospital, Harvard Medical School in Boston, reviewed where the field is currently with CAR T-cell therapy. She noted the theoretical short-term risks — local inflammatory reactions, CRS, ICANS, infection, and, rarely, immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome — as well as the theoretical long-term risks for hypogammaglobulinemia, long-term cytopenias, and genotoxicity, particularly for malignancy and infertility, though the latter has been extremely uncommon in the oncology literature, she said.

Wobma noted that several case studies and case series similar to the one presented at the meeting have been published by researchers from Italy, China, Germany, and Spain, most often with patients who have refractory lupus or refractory JDM.

“I want to highlight that some of them have been quite sick, including being either on a ventilator or on dialysis,” Wobma said. “They all received CD19-targeting products with variable follow-up and achieved drug-free remission, and the safety profile so far is generally encouraging.”

These early, encouraging studies show proof-of-concept, she said, but they are often emergency use scenarios, which means the patient population differs from a typical clinical trial population. Systematic data collection with longer term follow-up is necessary, she said.

“What’s really exciting for us as pediatric rheumatologists is that we have the potential to maybe cure our patients and spare them a lifetime of illness, but that also means that they have the longest horizon for potential disease recurrence,” especially with conditions such as pediatric-onset SLE, where greater genetic risk may exist, she said.

The challenge with enrolling patients in clinical trials, she said, is identifying patients with what is essentially a Goldilocks level of disease severity. Patients who are clinically stable are not sick enough to justify the risk-benefit ratio, whereas patients who are too sick are outside the feasibility window. The ideal patients are those who have partially, but not fully, managed SLE, JDM, systemic sclerosis, or antineutrophil cytoplasmic antibody-associated vasculitis. She also discussed possible strategies for clinically unstable patients.

“One wonders if less expensive, potentially less toxic approaches to severe disease should be explored simultaneously, such as combination rituximab and IV cyclophosphamide,” Cron told Medscape Medical News. “It is unclear if it is the deeper and more complete elimination of B cells that is the difference between CAR T and B cell-depleting monoclonal antibody approaches in terms of effectiveness.” New B cell-depleting antibodies, such as obinutuzumab, appear more effective than prior reagents, he said, so they may become treatments for pediatric SLE, JDM, and/or systemic sclerosis.

“The conditioning regimen involved in CAR T approaches may also play a role in their effectiveness and potential toxicity,” Cron also noted. “For now, anecdotal approaches using CAR T to treat severe pediatric rheumatic illnesses are accumulating, but ultimately prospective clinical trials will be needed for broader utilization.”

The research was funded by grants from the Italian government in the Ministry of Education, University and Research and Ministry of Business and Made in Italy; the European Union; the ‘Hub Life Science-Terapia Avanzata’ (from the Italian Ministry of Health); the IRCCS Ospedale Pediatrico Bambino Gesù; and the German Research Foundation. Miltenyi Biomedicine provided the viral supernatant used in the manufacture of zorpocabtagene autoleucel.

Bracaglia reported being a consultant for Sobi and Novartis and being a speaker for GSK. Two other coauthors reported disclosures with a variety of different industry companies for grants, speaking, or advisory board participation. Wobma reported holding equity in Regatta Bio. Cron reported receiving speaker, advising, committee work, and/or consulting fees and grant support from Sobi, Sironax, CareerPhysician, Neurogene, AS2 Biotherapeutics, Novartis, Lilly, AbbVie, and Pfizer.

Tara Haelle is a science/health journalist based in Dallas.