Single dose of CAR T-cell therapy puts 3 autoimmune diseases in remission
Case report: Woman remained off all other therapies more than a year later
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A woman with an extremely rare combination of three autoimmune diseases — immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and antiphospholipid syndrome — has been free of any symptoms since receiving a single dose of zorpocabtagene-autoleucel (zorpo-cel), an experimental CAR T-cell therapy developed by Miltenyi Biomedicine, according to a case report.
Researchers led by Fabian Müller, MD, a specialist in blood diseases at the University Hospital Erlangen in Germany, modified the woman’s own immune T-cells to target and eliminate the B-cells responsible for producing the self-reactive antibodies driving her three autoimmune diseases. She had no side effects from zorpo-cel, and more than one year later, at the time of their report, she remained off all other therapy.
“It was an entirely uncontrolled disease. And now she’s off any therapy. That tells you that, at least for now, we did something very right,” Müller said in a news story from Nature.
While zorpo-cel is still experimental, this case supports further testing beyond CASTLE (NCT06347718), a Phase 1/2 clinical trial sponsored by Miltenyi that includes patients with autoimmune diseases such as lupus and systemic sclerosis.
The case report, “CD19 CAR-T therapy induces remission in refractory autoimmune hemolytic anemia with ITP and antiphospholipid syndrome,” was published in Med.
‘Her disease got completely out of hand’
Autoimmune diseases are caused by self-reactive antibodies that drive a misdirected immune response in the body. In this woman’s case, immune B-cells were producing antibodies that attacked her own red blood cells, causing AIHA. These antibodies also attacked platelets, which normally help blood clot, causing ITP, and some fat-binding proteins, causing antiphospholipid syndrome.
The 47-year-old woman was first diagnosed with severe AIHA that did not respond to nine different lines of therapy, including rituximab, an antibody that depletes B-cells. Over time, she developed antiphospholipid syndrome, which caused repeated blood clots and required her to stay on long-term blood thinners, and ITP. She remained dependent on frequent blood transfusions.
“Her disease got completely out of hand” and became “very life-threatening,” Müller said.
Given the lack of effective options, she was treated under compassionate use with zorpo-cel, a CD19-directed CAR T-cell therapy. Compassionate use refers to access to a therapy that is not yet approved for use outside of a clinical trial.
CAR T-cell therapy involves collecting a patient’s own T-cells and genetically engineering them to recognize a protein called CD19 on B-cells. When these CAR T-cells encounter B-cells, they eliminate them. This is expected to reduce the production of self-reactive antibodies, easing symptoms.
After short-term chemotherapy to temporarily suppress the immune system, the woman received an infusion of 1 million of her genetically engineered CAR T-cells per kg. Following infusion, CAR T-cells rapidly expanded in her body. Circulating B-cells were “rapidly depleted,” the researchers wrote.
Clinical improvement was rapid: Within seven days, she no longer required blood transfusions, and her levels of hemoglobin, the protein that carries oxygen in red blood cells, normalized within less than one month.
Zorpo-cel was well tolerated by patient
Her platelets also increased and remained stable — at about half the lower limit of normal — from around two months after the infusion. About one month before receiving zorpo-cel, her platelets had briefly increased in response to intravenous (into-the-vein) immunoglobulins and corticosteroids. Previously elevated antiphospholipid antibodies gradually declined and eventually became undetectable.
Importantly, zorpo-cel was well tolerated. The patient did not experience cytokine release syndrome, a heightened immune response and body-wide inflammation, or neurotoxicity, damage to the nervous system, two common complications of CAR T-cell therapy. Aside from a transient increase in liver enzymes and a decrease in lymphocytes, a type of white blood cells that include T-cells and B-cells, no other side effects were observed.
At follow-up extending beyond one year, the woman remained in durable remission, meaning she experienced no symptoms. B-cells eventually began to reappear after CAR T-cells cleared, but they showed a “reset” naïve profile rather than the previous self-reactive profile. Clinically, she regained normal daily function, and long-term blood thinners were discontinued without new blood clots appearing.
Consistent with data from the CASTLE clinical study, in which most patients responded well to zorpo-cel by entering remission or experiencing no progression of symptoms, this case shows that CAR T-cell therapy can induce and sustain remission in severe autoimmune diseases that do not respond to standard therapy. However, given the single-patient nature of the report, “more data from controlled clinical trials are needed for final conclusions,” the researchers wrote.
