Short-term treatment may rapidly control hemolysis in secondary CAD
Enjaymo served as a bridge while cancer therapy targeted underlying CLL
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Enjaymo (sutimlimab) rapidly stopped hemolysis — destruction of red blood cells — while anti-cancer treatment targeted the underlying blood cancer believed to be driving secondary cold agglutinin disease (CAD) in a 61-year-old woman.
This case “adds to the growing evidence that using short-term [Enjaymo] for [secondary CAD] as a bridge to more durable treatment for underlying disorders like CLL [chronic lymphocytic leukemia] can be a highly effective and safe strategy,” the researchers wrote. CLL is a type of blood cancer.
Case report examines Enjaymo as bridge therapy
The woman’s case was described in the study “Treatment of Cold Agglutinin Syndrome Secondary to Chronic Lymphocytic Leukemia With Sutimlimab and Obinutuzumab–Venetoclax,” which was published in Case Reports in Hematology by two researchers at MedStar Georgetown University Hospital in Washington.
CAD is caused by self-reactive antibodies called cold agglutinins that bind to red blood cells at lower temperatures, triggering immune-system reactions that can destroy the cells.
While it can occur on its own — known as primary CAD — cold agglutinin-related disease can also occur secondary to another condition, such as an infection or blood cancer. In such cases, it’s called secondary CAD, or cold agglutinin syndrome (CAS).
Treating secondary CAD focuses on treating the underlying disease. However, treatment for an underlying blood cancer may take “weeks to months” to produce a response, the researchers wrote.
Here, the scientists reported on the use of Enjaymo as a temporary bridge treatment to control hemolysis, which contributes to symptoms of CAD, while waiting for more definitive treatment of the underlying blood cancer to take effect.
Enjaymo is an approved treatment for CAD that is indicated for the treatment of hemolysis in adults with the disease. It works by blocking C1s, a protein needed to activate the complement cascade, part of the immune system that contributes to red blood cell destruction in CAD. By blocking C1s, Enjaymo interrupts this chain of immune reactions.
Woman’s secondary CAD develops alongside CLL
In this 61-year-old woman, secondary CAD was associated with CLL, a blood cancer that develops in B cells, the immune cells that produce antibodies.
About eight years before she was evaluated in 2018, she developed bluish discoloration of her fingers and toes when exposed to cold. She also had livedo reticularis, a net-like purplish pattern on the skin caused by changes in small blood vessels.
Testing showed a high level of cold agglutinins. Her direct Coombs test, which detects antibodies or complement proteins attached to red blood cells, was strongly positive for C3d, a component of the complement system.
Her bone marrow — the spongy tissue that fills the center of most bones, where blood cells are produced — contained a small population of abnormal B cells with features seen in CLL.
“A diagnosis of CAS in the setting of [a CLL-related B-cell condition] was made,” the researchers wrote. They added that because of limited symptoms and patient preference, a “watch-and-wait” strategy was pursued, meaning that close monitoring was preferred over immediate treatment.
Over the following years, her symptoms worsened. Her cold agglutinin levels increased, her hemoglobin — the oxygen-carrying protein in red blood cells — fell below the normal range, and markers of hemolysis increased. More than half of her bone marrow contained CLL cells.
Because her anemia — a condition marked by too few red blood cells or too little hemoglobin — had become severe and symptomatic, doctors started her on Enjaymo to rapidly control hemolysis so she could tolerate treatment for the underlying CLL. At the same time, she received Calquence (acalabrutinib), an anti-cancer treatment. Within about two weeks, however, her anemia worsened, markers of hemolysis remained elevated, and she developed debilitating weakness.
Calquence was stopped, after which her anemia began improving and her weakness gradually resolved.
Doctors switch cancer therapy while continuing Enjaymo
The doctors then decided to continue Enjaymo but switch her CLL treatment to a combination of Gazyva (obinutuzumab), which targets B cells, and Venclexta (venetoclax), which helps cause cancer cells to die.
About four weeks after starting Enjaymo, markers of hemolysis began to improve and her hemoglobin increased. After six months, her hemoglobin had returned to the normal range, and her fatigue and cold-related skin discoloration had returned to baseline.
By May 2025, treatment with Gazyva had been completed, and Enjaymo had also been stopped after serving as short-term bridge therapy. After Enjaymo was stopped, her hemoglobin remained within the normal range. The researchers noted that complement inhibition with Enjaymo does not address the underlying production of self-reactive antibodies, but in this case the drug was used as a bridge while treatment targeted the underlying CLL.
“For patients with CAS secondary to CLL requiring rapid control of hemolysis, using short-term [Enjaymo] as a bridge toward more durable treatment for CLL with [Gazyva-Venclexta] is a highly effective and safe treatment strategy,” the researchers wrote.
One of the study authors reported receiving research support and honoraria from Sanofi and Recordati; the other reported no conflicts of interest.
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