Managing acute hemolysis in PNH with Empaveli can be challenging
Researchers write about woman, 32, in Italy diagnosed with PNH in 2018
Increasing dosing of Empaveli (pegcetacoplan) followed by co-administering Soliris (eculizumab) effectively managed acute red blood cell destruction in a woman with paroxysmal nocturnal hemoglobinuria (PNH), a study shows.
The effort underscores how acute red blood cell destruction “requires prompt diagnosis and treatment to avoid potentially life-threatening events,” the researchers said. The study, “Severe breakthrough hemolysis during compassionate use of Pegcetacoplan in paroxysmal nocturnal hemoglobinuria: managing an emergency,” was published in Blood Transfusion.
PNH occurs when the complement system, a part of the immune system that normally helps fight off infections, becomes activated and mistakenly attacks and destroys blood cells, particularly red blood cells. Empaveli prevents complement activation by targeting C3, a protein that regulates its activation, making it able to help prevent hemolysis, that is, red blood cell destruction, and ease PNH symptoms.
The therapy was approved in the U.S. and then in Europe for PNH in 2022, where it’s sold under the name Aspaveli, for adults with PNH who remain anemic after being treated with C5 inhibitors for at least three months and those who’d never had treatment.
Researchers in Italy write about a 32-year-old woman who had breakthrough hemolysis and saw her PNH symptoms return despite taking Empaveli.
Initial resolution of PNH symptoms
The woman was diagnosed with PNH in October 2018 and started Soliris in January 2019, which led to a complete resolution of her hemolysis.
Iin July 2019, however, she was diagnosed with severe aplastic anemia, which occurs when the bone marrow becomes unable to produce enough new blood cells for the body to work normally.
Since no suitable bone marrow donor was found, she was treated with a medication to increase her low platelet counts, along with other supportive therapies. Platelets are blood cell fragments involved in blood clotting.
In September 2021, she had a hemolysis episode and restarted Soliris, but after this 900 mg every 14 days failed to control her hemolysis. In February 2022, the woman was admitted to another center in search of an alternative treatment. She complained of general physical weakness and abdominal pain.
Blood work revealed abnormalities and Empaveli, which hadn’t yet been approved in Italy, was started under a compassionate use program. The woman started the therapy at 1,080 mg twice a week in May 2022. Soliris was also maintained in the first four weeks.
A month later, lab work showed improvements in several blood-related parameters. The woman was taught to self-administer Empaveli and was able to continue treatment at home. Levels of hemoglobin, the protein responsible for transporting oxygen in red blood cells, markedly increased and there were no signs of hemolysis nor drug-related side effects.
Hemolysis returns
In early September 2022, the woman became nauseous and started vomiting. She was discharged from the emergency department once her symptoms were managed without having any lab work, but returned a day later with abdominal cramps, persistent vomiting, and diarrhea. A CT scan revealed thickening in the first section of her large intestine, called the cecum, and swelling in nearby tissues. Blood work showed signs of severe hemolysis, including low hemoglobin.
She received antibiotics along with heparin, a blood thinner. The dosage of Empaveli was increased to 1,080 mg every three days, with blood transfusions, if needed.
Tests showed signs of kidney damage and two weeks of hemodialysis were needed before the woman’s kidney function spontaneously recovered. Hemolysis also was controlled, as shown by increased hemoglobin.
But four days later, the woman had a sudden breakthrough hemolysis episode. Physicians added Soliris to her treatment plan, which led to a partial response. A second dose of Soliris was administered after 14 days. Cecum inflammation was deemed to be the most likely cause.
The woman was discharged and put on a standard dosing schedule of Empaveli. Hemolysis was kept under control.
The researchers said the case highlights the challenges of managing PNH patients on Empaveli. While no guidelines are available for managing breakthrough hemolysis in the patients, “both shortening the interval between doses or intravenous administration of [Empaveli] and [Soliris] pulses if life-threatening conditions are present should be promptly adopted,” they said, adding recognizing a severe episode is paramount to avoid complications that may be life-threatening.
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