Rituximab-fludarabine combination therapy has been recommended as a first-line treatment for cold agglutinin disease (CAD). Rituximab and fludarabine are both approved for the treatment of certain types of cancer, including chronic lymphocytic leukemia.
How rituximab-fludarabine combination therapy works
CAD is a rare disease in which the immune system mistakenly attacks the red blood cells in cold temperatures, causing them to lyse, or burst. As is the case with many autoimmune diseases, it is not clear what causes the immune system to attack the red blood cells in CAD.
Rituximab is an antibody that recognizes specific immune cells that produce antibodies and binds to them, targeting them for destruction. That reduces their number. Rituximab may be able to reduce the immune attack on red blood cells in CAD by reducing the amounts of antibodies produced that target red blood cells.
Fludarabine is a small molecule that is metabolized by the body into a molecule that inhibits DNA synthesis. Blocking DNA synthesis strongly affects those cells that rely on rapid cell division — like immune cells. In this way, fludarabine suppresses the immune system and may be able to reduce the attack on red blood cells in CAD.
Rituximab-fludarabine combination therapy in clinical trials
The results of a previous Phase 2 clinical trial (NCT00373594) were published in the journal Blood. A total 29 CAD patients received rituximab on day 1, 29, 57, and 85 of the trial. These individuals also took fludarabine orally on days 1 through to 5, 29 through 34, 57 through 61, and 85 through 89. A total 22 patients (76%) responded to treatment. Among them, six showed no signs of CAD at the end of treatment, and 16 showed a significant partial response to the therapy.
Patient response was measured by the level of hemoglobin in the blood, a measure of red blood cell number. Researchers note that hemoglobin is the protein in red blood cells that carries oxygen.
The investigators concluded that rituximab-fludarabine combination therapy is very effective. However, they noted that several patients experienced toxicity as a result of treatment, which should be taken into account when choosing this combination therapy.
Last updated: August 15, 2019
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