CD19 CAR-T therapy induces remission in refractory autoimmune hemolytic anemia with ITP and antiphospholipid syndrome, 2026, Korte et al

CD19 CAR-T therapy induces remission in refractory autoimmune hemolytic anemia with ITP and antiphospholipid syndrome, 2026, Korte et al

CD19 CAR-T therapy induces remission in refractory autoimmune hemolytic anemia with ITP and antiphospholipid syndrome

Korte, Isabel K.; Kharboutli, Soraya; Völkl, Simon; Heberling, Lisa; Scholz, Julia K.; Pfeiffer, Hella; Strobel, Julian; Harrer, Thomas; Kretschmann, Sascha; Vasova, Ingrid; Gerbitz, Armin; Achenbach, Susanne; Spriewald, Bernd; Krause, Stefan; Gutsche, Kerstin; von Bonin, Malte; Röllig, Christoph; Aigner, Michael; Mackensen, Andreas; Müller, Fabian

Abstract
Background
Autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), and antiphospholipid antibody syndrome (APLAS) are B cell-driven autoimmune diseases defined by pathogenic autoantibodies. CD19-directed chimeric antigen receptor (CAR)-T cells have recently demonstrated the ability to reset dysregulated B cells and induce long-lasting remission in refractory systemic autoimmune diseases. Evidence for efficacy in severe, treatment-refractory AIHA, however, is limited.

Methods
We report the clinical course of a 47-year-old woman with life-threatening cold- and warm-agglutinin AIHA refractory to nine prior treatment lines, accompanied by ITP and APLAS. In an uncontrolled flare, she received a fludarabine/cyclophosphamide-containing lymphodepletion followed by autologous CD19-directed, 4-1BB-costimulated CAR-T cells (zorpocabtagene-autoleucel [Zorpo-cel], 1 × 106/kg) on the basis of compassionate use. Treatment efficacy and safety were assessed over an 11-month follow-up period.

Findings
Zorpo-cel showed a rapid and sustained B cell depletion. Transfusion independence was achieved by day 7, with hemoglobin normalization by day 25, including resolution of hemolysis markers. Cold-agglutinin titers decreased, and previously elevated antiphospholipid antibodies normalized without recurrence throughout 11 months of follow-up. ITP stabilized. No cytokine release syndrome or neurotoxicity occurred. Mild transaminase elevation and thrombocytopenia were observed, most likely correlating with pre-existing severe iron overload due to erythrocyte transfusions.

Conclusion
This case demonstrates that CD19-directed CAR-T cell therapy can induce rapid, durable remission of severe, refractory cold-agglutinin AIHA and simultaneously improve coexisting APLAS and ITP on a favorable toxicity profile. However, more data from controlled clinical trials are needed for final conclusions.

Web | DOI | Med
 
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