Cell therapy helps woman with rare combination of 3 diseases
Single dose of experimental treatment eased CAD symptoms
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A single dose of the cell therapy candidate zorpocabtagene-autoleucel (zorpo-cel) led to rapid, durable symptom relief in a woman with severe, hard-to-treat cold agglutinin disease (CAD) in a rare combination with two other autoimmune disorders, a case study reported.
The woman had been dependent on blood transfusions for her CAD and had tried multiple therapies, but none effectively managed her condition. Within a week after receiving one-time treatment with zorpo-cel, she was able to stop receiving blood transfusions. More than a year later, her condition has remained stable without symptoms or the need for any additional treatment.
“Her disease got completely out of hand” and became “very life-threatening,” Fabian Müller, MD, a blood disease specialist at University Hospital Erlangen in Germany and the study’s senior author, said in a news story from Nature. “Now she’s off any therapy. That tells you that, at least for now, we did something very right.”
The case study, “CD19 CAR-T therapy induces remission in refractory autoimmune hemolytic anemia with ITP and antiphospholipid syndrome,” was published in Med.
Cell deregulation
Most autoimmune diseases are marked by problems with B cells, the immune cells that produce antibodies, including those that mistakenly target the body’s healthy cells. The B-cell dysregulation that drives the development of one autoimmune disease can also increase the chances of a second.
In people with CAD, these self-reactive antibodies stick to red blood cells at low temperatures, causing the cells to clump and be destroyed. This leads to CAD symptoms such as anemia (low red blood cell levels) and impaired oxygen transport throughout the body, which can become life-threatening.
The 47-year-old woman at the center of the report had been diagnosed with CAD in 2014. She tried nine different immunosuppressive treatments, including multiple rounds of rituximab, a B-cell-depleting therapy sold as Rituxan and others, with biosimilars available.
None of these therapies worked, and she required regular blood transfusions. She would go through a whole bag of red blood cells on an average day, and on some days, she needed as many as three.
A year after her initial diagnosis, she was diagnosed with antiphospholipid antibody syndrome (APLAS), an autoimmune disease marked by antibodies that target fat-binding proteins, making blood more likely to clot.
A few years after that, in 2019, she was diagnosed with immune thrombocytopenia (ITP), an autoimmune bleeding disorder characterized by antibodies that attack platelets (the cell fragments that help blood clot), increasing the risk of bleeding.
By the time she was referred for zorpo-cel under a compassionate use program in 2025, she was no longer able to work. Pain and fatigue often left her unable to get out of bed for days or weeks at a time.
Compassionate use programs allow experimental therapies to be given to patients with certain serious or life-threatening conditions outside clinical trials.
“It was her last chance,” Müller said, “for controlling the disease.”
Doctors try a Hail Mary
Zorpo-cel, also called MB-CART19.1, is a CAR T-cell therapy developed by Miltenyi Biomedicine for a range of autoimmune diseases and blood cancers.
The treatment involves harvesting T-cells, a type of immune cell that can kill other cells, from a patient. The cells are then engineered in the lab to carry a chimeric antigen receptor, or CAR, that targets CD19, a protein present in B-cells. This CAR works like a human-made molecular weapon, directing T-cells to attack B-cells. The engineered cells are then infused back into the patient.
The hope was that the CAR T-cells could wipe out the woman’s B-cells, in a last-chance attempt to control her autoimmune diseases. Before receiving a one-time infusion of zorpo-cel, the woman received chemotherapy aimed at depleting her existing immune cells to make room for the therapeutic T-cells.
Overall, she tolerated the therapy well, without any of the harmful side effects sometimes seen with CAR T-cell therapy. Counts of certain immune cells (a common side effect of CAR T-cell and chemotherapy) were very low, but this condition was less severe at the last follow-up.
Her condition rapidly improved. In addition to becoming independent from transfusions after a week, blood levels of hemoglobin (the protein that red blood cells use to carry oxygen) normalized after less than a month.
The researchers noted that CAR T-cell therapies have been successfully deployed to treat CAD, APLAS, or ITP individually, but this is the first documented case where this type of treatment resolved all three diseases co-occurring in the same person.
“We are the first to achieve treatment-free remission in a complex case of three distinct [autoimmune diseases] by a single infusion of … CAR-T cells,” the scientists wrote.
Miltenyi was not directly involved in the study, though some of the co-authors have received funding from the company in the past.
