Woman with CAD develops B-cell cancer during treatment
She was being treated with Enjaymo, the only approved CAD therapy
A woman with cold agglutinin disease (CAD) developed an aggressive B-cell lymphoma after having only a brief response to Enjaymo (sutimlimab), according to a case report.
Researchers said the “case highlights the importance of reassessing underlying conditions through [a bone marrow biopsy] in cases where [Enjaymo] treatment is ineffective,” given that an abnormal growth of immune B-cells in bone marrow drives most CAD cases and that, in some cases, it may progress to an aggressive B-cell cancer. The study, “A Case of Cold Agglutinin Disease With Transformation to High-Grade Lymphoma During Sutimlimab Treatment,” was published in Cureus.
CAD is caused by self-reactive antibodies called cold agglutinins. The antibodies bind to red blood cells at low temperatures, setting off the complement system, an immune cascade where one protein activates the next, ultimately leading to the destruction of red blood cells, called hemolysis. This leads to anemia, low red blood cell counts, and symptoms such as fatigue. The disease is typically driven by an abnormal, but slow growth of B-cells in the bone marrow, where blood cells are made.
Recordati’s Enjaymo, which suppresses the complement system, is the only approved therapy for CAD. It’s cleared in the U.S., European Union, and Japan to reduce hemolysis in adults.
“CAD typically follows an indolent course and has a generally favorable prognosis,” but transformation into an aggressive B-cell lymphoma “has been reported in approximately 3.5% of patients during a 10-year follow-up period,” the researchers wrote.
Temporary improvement with Enjaymo
In this case, a 67-year-old Japanese woman with CAD developed a rapidly growing B-cell lymphoma during treatment with Enjaymo.
She visited a local clinic after having upper abdominal pain and fatigue with physical activity. Blood tests showed macrocytic anemia, a condition where red blood cells are larger than normal and fewer in number, and low hemoglobin, the protein responsible for carrying oxygen in red blood cells.
Follow-up tests revealed several signs of hemolysis-related anemia, including high levels of two hemolysis markers, lactate dehydrogenase (LDH) and bilirubin. A direct Coombs test, which detects antibodies and complement proteins attached to red blood cells, was positive. The woman also had very high levels of cold agglutinins. A bone marrow biopsy revealed an abnormal growth of B-cells, although there were no signs of B-cell lymphoma.
The woman was diagnosed with CAD associated with abnormal, but slow B-cell growth in the bone marrow.
She was started on Enjaymo, first weekly and then every two weeks. Her hemoglobin increased, reaching near-normal levels after the third dose. After the fourth dose, however, her hemoglobin levels dropped again and LDH levels increased.
The woman was found to have high blood levels of IgM, an antibody that drives CAD, and soluble IL-2 receptor, a molecule typically found at high levels in lymphomas.
An imaging test showed an increased use of energy in the bone marrow, consistent with a second biopsy that revealed large, abnormal B-cells that multiplied rapidly, therefore requiring more energy. These lab, imaging, and tissue findings suggested a transformation into aggressive, high-grade B-cell lymphoma.
Enjaymo was stopped after five doses and the woman began a chemotherapy regimen known as Pola-R-CHP. Her anemia soon declined and, after six cycles of chemotherapy, imaging confirmed complete remission, no signs of the B-cell lymphoma. The woman “has remained stable without recurrence of either lymphoma or anemia,” the researchers wrote.
“In our case, [Enjaymo] temporarily improved anemia; however, it subsequently worsened,” the researchers wrote, noting a repeat bone marrow biopsy may be needed when treatment for CAD is not effective. They said that, while “transformation is rare, careful monitoring for disease progression during [Enjaymo] treatment remains crucial.”
About the Author
