Zorpocabtagene autoleucel

Researchers at University Hospital Erlangen in Erlangen, Germany report that a single infusion of CD19 CAR-T therapy in autoimmune hemolytic anemia produced sustained remission in a patient with overlapping refractory AIHA, immune thrombocytopenia, and antiphospholipid syndrome, according to a study published April 10, 2026 in Med. The patient had failed nine prior treatment lines, including three courses of rituximab. The case involved a 47-year-old woman with concurrent cold- and warm-agglutinin autoimmune hemolytic anemia, ITP, and antiphospholipid antibody syndrome — a combination of autoantibody-driven disorders sharing a common pathogenic mechanism in dysregulated B cells. Prior therapies including steroids, intravenous immunoglobulin, azathioprine, bortezomib, and repeated rituximab had each failed to produce durable control. The treating team at Erlangen administered zorpocabtagene-autoleucel (Zorpo-cel; MB-CART19.1), an autologous 4-1BB-costimulated CD19-directed CAR-T cell product manufactured on the Miltenyi Prodigy platform, at a dose of 1 × 10⁶ CAR-positive T cells per kilogram following lymphodepletion with fludarabine and cyclophosphamide. Hematologic recovery was rapid. The patient achieved transfusion independence by day 7 and hemoglobin normalization above 12 g/dL by day 25. Hemolysis markers including LDH and haptoglobin normalized, and reticulocyte counts stabilized. Warm-reactive autoantibodies became undetectable, cold agglutinin titers fell, and antiphospholipid antibodies declined. Platelet counts improved without additional ITP-directed therapy. These responses were maintained across the 11-month follow-up period. The direct antiglobulin test showed conversion, and CAR-T cells demonstrated in vivo expansion detectable in peripheral blood following infusion. At approximately day 322, reconstituted B cells were 98% naïve phenotype, indicating that the reconstituting immune compartment lacked the autoreactive memory imprinting present before treatment. The safety profile was consistent with CAR-T cell therapy autoimmune hemolytic anemia experience in oncology settings. The patient developed Grade 1–2 cytokine release syndrome managed with tocilizumab and supportive care. No immune effector cell-associated neurotoxicity syndrome was observed. Hypogammaglobulinemia, an expected consequence of B cell depletion, was managed with immunoglobulin replacement. No treatment-related mortality or life-threatening infections occurred. The biological rationale for CD19-directed CAR-T cells in this setting centers on the shared dependence of AIHA, ITP, and antiphospholipid syndrome on autoreactive B cells producing pathogenic autoantibodies. CD19 is expressed across the B cell lineage, including on subsets and in tissue compartments where the anti-CD20 monoclonal antibody rituximab achieves incomplete penetration. The Erlangen authors note that CAR-T cells achieved remission despite three prior rituximab failures, consistent with the hypothesis that deeper and more anatomically complete B cell depletion — including in lymph nodes and mucosal compartments — underlies the more durable response. The 4-1BB costimulatory domain incorporated into Zorpo-cel is associated with enhanced CAR-T cell persistence and memory differentiation, which may contribute to the duration of response observed. The authors describe the qualitative change in the reconstituted B cell compartment as a key mechanistic finding. The near-complete naïve phenotype of returning B cells at day 322 suggests that pathogenic memory clones were eliminated and that immune reconstitution proceeded from progenitors without the autoimmune programming that had driven disease. The authors characterize this as a B cell reset rather than simple depletion, distinguishing the approach from conventional immunosuppression, which does not eliminate autoreactive memory. The Erlangen group has previously reported CD19 CAR-T outcomes in systemic lupus erythematosus, inflammatory myositis, and systemic sclerosis, establishing the broader concept of CAR-T-mediated immune reset in connective tissue diseases. The current report extends that work to autoimmune cytopenias — a distinct disease category where dedicated CAR-T data remain limited. Refractory AIHA treatment options after rituximab failure are constrained. Fostamatinib, a spleen tyrosine kinase inhibitor, carries regulatory approval for warm AIHA but does not address the underlying autoantibody mechanism. Sutimlimab targets complement component C1s and is approved specifically for cold agglutinin disease but does not eliminate pathogenic B cells. Thrombopoietin receptor agonists for ITP and anticoagulation for antiphospholipid syndrome address downstream consequences without modifying the autoimmune source. In the commercial CAR-T space, Kyverna Therapeutics is advancing KYV-101, a CD19-directed autologous CAR-T product, in Phase II trials across multiple autoimmune indications including multiple sclerosis, myasthenia gravis, and systemic sclerosis. Cabaletta Bio is running Phase I/II RESET trials with CABA-201 in inflammatory myositis and lupus. Neither program is specifically focused on autoimmune cytopenias, and the current report from Erlangen represents one of the few published accounts of antiphospholipid syndrome CAR-T treatment alongside AIHA and ITP in a single patient. Prof. Dr. Fabian Müller of University Hospital Erlangen served as corresponding author. The work was funded by the Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, the Bundesministerium für Bildung und Forschung, the Bayerisches Zentrum für Krebsforschung, the Interdisciplinary Center for Clinical Research Erlangen, and the Staedtler Foundation. Miltenyi Biotechnology provided the manufacturing platform and research support to authors at the institution. Meta description: Erlangen researchers report CD19 CAR-T remission in refractory autoimmune hemolytic anemia with concurrent ITP and antiphospholipid syndrome. Your email address will not be published. Required fields are marked * Comment * Name * Email * Website