Cancer drug triggers 2-year recovery for woman with rare blood disorder
Patient with resistant iTTP saw crucial enzyme activity restore after treatment
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Four weekly injections of the antibody therapy daratumumab restored a key enzyme’s activity and triggered a two-year recovery for a woman with hard-to-treat immune-mediated thrombotic thrombocytopenic purpura (iTTP), according to a case report.
In iTTP, the immune system produces antibodies that target the ADAMTS13 enzyme, preventing it from working properly. Initially lower than 5%, the 60-year-old patient’s ADAMTS13 activity increased to 86.8% after receiving daratumumab. Two years later, she remained well, with normal blood tests.
“Daratumumab [Darzalex] showed to be a safe, efficient and long lasting option for additional immunosuppressive therapy for early relapsed iTPP in this case,” researchers wrote.
“An attentive follow up of iTTP patients is needed in order to predict early relapses and provide appropriate early treatment,” they added.
The report, “Relapsed thrombotic thrombocytopenic purpura and daratumumab utility,” was published in the journal Transfusion and Apheresis Science.
How iTTP impacts the body
TTP is a blood disorder in which tiny clots form throughout the body, potentially damaging organs such as the brain, heart, and kidneys. Treatment typically begins with therapeutic plasma exchange, which removes harmful antibodies and restores the ADAMTS13 enzyme’s activity. Other treatments include corticosteroids, Cablivi (caplacizumab), and rituximab.
Early relapses in iTTP occur in about 30%–50% of patients, underscoring the importance of long-term monitoring. Daratumumab, an antibody therapy that targets antibody-producing plasma cells, has recently emerged as a possible treatment option. The antibody is sold as Darzalex by Johnson & Johnson and is an approved treatment for multiple myeloma.
In the report, investigators in Ireland described the use of daratumumab in a patient with relapsed and treatment-resistant iTTP.
The woman had a history of ulcerative colitis (UC) and was admitted to the hospital after three days of right-sided chest pain and general discomfort. UC is a form of inflammatory bowel disease that causes inflammation and ulcers in the lining of the large intestine. She had recently reduced her daily dose of prednisolone to control inflammation and started budesonide, another corticosteroid, the day before admission.
On examination, she had bruising that increased during the first hours after admission and a mildly elevated heart rate. Blood tests showed anemia with low hemoglobin (the protein that carries oxygen in red blood cells), a low platelet count, and signs of red blood cell destruction. A blood smear revealed the presence of schistocytes, or fragmented red blood cells, supporting a diagnosis of microangiopathic hemolytic anemia, in which red blood cells are damaged and destroyed as they pass through small blood vessels blocked by clots or vessel injury.
She also had elevated troponin, a marker of heart injury, but her kidney and liver function were normal.
The woman was transferred immediately to an intensive care unit and started on daily therapeutic plasma exchange, along with high-dose methylprednisolone and other therapies. Within the first 12 hours, she experienced confusion and asystole (when the heart’s electrical system fails entirely and stops pumping), but she recovered fully after resuscitation measures.
Lab tests showed that her ADAMTS13 enzyme activity was lower than 5%, along with high levels of an antibody inhibitor against the enzyme, confirming iTTP. Cablivi, a therapy approved for iTTP, was not available, so treatment continued with plasma exchange and corticosteroids. Rituximab was added on the second day and given once weekly thereafter.
Imaging showed multiple blood clots in the lungs, known as pulmonary emboli. However, blood-thinning treatment could not be started immediately because the woman’s low platelet count increased the risk of bleeding.
By the third day, her platelet count had risen, allowing aspirin to be started. Anticoagulation with enoxaparin was added the following day to treat the lung clots.
Her platelet counts continued to increase by day five. She remained clinically stable, received plasma exchange for a total of eight days, and was discharged two weeks after admission. At discharge, she was taking the blood thinner apixaban, along with prednisolone, rituximab, and her other long-term medications.
Despite four weekly rituximab doses and normal blood cell counts, laboratory tests continued to show signs of red blood cell destruction. ADAMTS13 activity remained lower than 5%, suggesting a risk of relapse.
With the goal of using a different immunosuppressive treatment, the clinicians obtained approval to use daratumumab as an off-label medication, meaning the therapy is being used for an indication not on the prescribing label. The woman received four weekly injections under the skin.
After the second dose, ADAMTS13 activity improved to 62.9%. After the fourth dose, it increased further to 86.8%.
Two years later, the woman remained clinically well, with normal blood work.
“Regular monitoring of haemolysis [red blood cell destruction] markers as well the ADAMTS13 enzyme levels were the most important parameters in the follow-up of this case,” the investigators wrote.
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