Real-world data show Enjaymo reduces blood cell loss in CAD
Study finds rapid, sustained action, lower need for blood transfusions
Written by |
Enjaymo (sutimlimab-jome) rapidly and sustainably reduces red blood cell destruction and the need for blood transfusions in most adults with hard-to-treat cold agglutinin disease (CAD) in real-world clinical settings, a study showed.
“[Enjaymo] demonstrated rapid, durable effectiveness and a favorable safety profile in heavily pretreated real-world CAD patients,” the researchers wrote.
Still, cold-induced symptoms in the extremities, such as bluish discoloration of the skin (acrocyanosis), persisted and were associated with lower response rates.
The study, “Safety and Effectiveness of Sutimlimab in Cold Agglutinin Disease: A Real-World International Experience,” was published in the American Journal of Hematology.
In CAD, self-reactive antibodies called cold agglutinins mistakenly attack red blood cells at cold temperatures. Such attacks activate the complement cascade, a part of the immune system, leading to red blood cell destruction (hemolysis) and disease symptoms.
Studies show effectiveness, but real-world studies have been few
Enjaymo, given via intravenous (into-the-vein) infusion every two weeks, is a complement-suppressor therapy approved to reduce hemolysis in adults with CAD, aiming to ease symptoms and improve quality of life.
While clinical trials have demonstrated Enjaymo’s effectiveness in reducing hemolysis and the need for CAD patients to undergo blood transfusions, real-world evidence remains sparse.
To fill this gap, the team conducted a study to assess the real-world safety and effectiveness of Enjaymo in CAD patients living in several European countries, Australia, and Japan. They retrospectively analyzed data from 57 adults with CAD (56% women), with a median age of 73.5 at the start of Enjaymo treatment.
At diagnosis, 54% had cold-induced peripheral symptoms, or symptoms affecting the extremities, including acrocyanosis, uneven facial skin tone, and tissue death in the fingers or toes.
Before starting Enjaymo, participants had taken a median of two prior therapies, most commonly corticosteroids and rituximab (sold as Rituxan and others, with biosimilars available). In the six months before starting Enjaymo, patients received a median of two red blood cell transfusion units.
These therapeutic approaches had limited success, as indicated by signs of active hemolysis and low levels of hemoglobin, the protein in red blood cells that carries oxygen, before Enjaymo initiation.
After two weeks of Enjaymo, median hemoglobin levels rose from 8.9 to 10.9 g/dL. By four weeks, these reached a median of 12 g/dL, approaching the normal adult range of 12 g/dL to 17.5 g/dL. From week eight through 24 months (two years), hemoglobin remained relatively stable, with median values between 11.4 g/dL and 12.2 g/dL.
Blood levels of hemolysis markers also fell rapidly, as early as two weeks.
Enjaymo treatment “was associated with a rapid and sustained increase in hemoglobin levels, paralleled by an early and durable normalization of biochemical markers of hemolysis,” the team wrote.
Within the first two weeks of treatment, about 30% had achieved a complete response, defined as hemoglobin levels above 12 g/dL and normalization of all hemolysis markers. Nearly half (45%) reached a partial response, while 15% showed an increase in hemoglobin of at least 1.5 g/dL.
At 12, 18, and 24 months, 55% to 60% of participants experienced a complete response, 25% to 30% showed partial responses, and 10% of patients saw their hemoglobin rise by about 10%.
Eight patients (14%) required blood transfusions. Most of those had not responded to Enjaymo or had experienced hemolysis exacerbations.
Enjaymo had no effect on cold-induced peripheral symptoms, and statistical analyses suggested that these symptoms were significantly associated with a lower response rate to Enjaymo.
Also, more non-responders than responders (63% vs. 26%) showed a limited decrease in the production of immature red blood cells (reticulocytes) in the bone marrow, which is typically high when red blood cell counts are low, as in CAD. Recombinant (lab-made) erythropoietin, a hormone that stimulates red blood cell production, was given to manage inadequate reticulocyte response.
“Inadequate bone marrow emerged as a predictor of suboptimal response, supporting the consideration of adjunctive recombinant erythropoietin in selected patients,” the team wrote.
More non-responders had also required blood transfusions in the six months before Enjaymo (87% vs. 54%) or had previously failed to respond to rituximab (50% vs. 26%), indicating more severe disease.
The estimated event-free survival, the length of time patients remained free of major disease events, was 88.1% at 12 months, 79.1% at 18 months, and 67% at 24 months.
After a median follow-up of 26 months, most patients (79%) remained on treatment. Reasons for discontinuation were a non-response, patient preference, disease progression, or adverse events.
Moderate to severe adverse events occurred in 12% of participants. Infectious complications were the most notable safety concern, affecting 23% of patients. Breakthrough hemolysis occurred in nine patients (16%), six of whom required blood transfusion, with a median hemoglobin recovery time of two months.
“[Enjaymo] demonstrated sustained real-world effectiveness in more than 70% of patients, leading to meaningful control of hemolysis and a reduction in transfusion requirements,” the researchers wrote.
