Autoimmune hemolytic anemia (AIHA) is a rare but serious immune-mediated disorder characterized by the destruction of red blood cells due to persistent autoreactive B-cell activity. Although many patients initially respond to corticosteroids or immunosuppressive therapies, relapse is common. Outcomes are particularly poor in multirefractory AIHA, a severe form of the disease defined by failure to respond to at least three lines of treatment. For these patients, therapeutic options are limited and often associated with long-term toxicity.
Building on the success of CD19-directed chimeric antigen receptor (CAR) T-cell therapy in hematologic malignancies and selected autoimmune conditions, Ruonan Li, MD, from the Institute of Hematology and Blood Diseases Hospital in Tianjin, China, and colleagues explored its role in multirefractory AIHA. Their findings were published in The New England Journal of Medicine.
The investigators enrolled patients through a compassionate-use program and an early-phase clinical trial. All participants had primary multirefractory AIHA and received a single infusion of autologous CD19 CAR T cells. The primary aim was to evaluate safety, with close monitoring for known CAR T-cell–related adverse events such as cytokine-release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). Secondary objectives included treatment efficacy, durability of remission, and biological mechanisms underlying response and relapse.
Key Findings:
• Eleven patients with multirefractory autoimmune hemolytic anemia were treated, including five through compassionate use and six in a phase 1 study.
• All patients achieved a complete response during a median follow-up of just over 12 months.
• The median time to complete response was 45 days, indicating rapid clinical improvement.
• Drug-free remissions were durable, with a median duration of 11.5 months and some patients remaining in remission for nearly two years.
• Most patients experienced mild to moderate cytokine-release syndrome, with grade 1 or 2 events reported in nine individuals.
• Low-grade neurotoxicity occurred in one patient, with no cases of severe (grade 4 or higher) cytokine-release syndrome or immune effector cell–associated neurotoxicity syndrome.
• Infections were observed in several patients but were manageable, and one case of grade 3 hematologic toxicity was reported.
• Multi-omics analyses showed that patients in sustained remission had B-cell reconstitution dominated by naïve B cells.
• Relapse was associated with a distinct immune niche involving interactions between specific B-cell and T-cell populations and long-lived plasma cells.
Overall, the study demonstrates that CD19 CAR T-cell therapy can induce sustained, drug-free remission in patients with multirefractory AIHA, with an acceptable safety profile. While larger studies are needed, these results suggest that CAR T-cell therapy may represent a transformative treatment option for severe autoimmune diseases beyond oncology.
Reference:
Li R, et al "CD19 CAR T-cell therapy for autoimmune hemolytic anemia" N Engl J Med 2026; DOI: 10.1056/NEJMoa2509820.
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