Rituximab and Bendamustine Combination Therapy

The combination of rituximab and bendamustine is an investigational approach for the treatment of cold-agglutinin disease (CAD).

In CAD, the immune system produces harmful autoantibodies called cold agglutinins. When the body experiences cold temperature, these antibodies attach to the surface of red blood cells, clumping them together and triggering their premature breakdown by the immune system. The clumping of red blood cells can clog the blood vessels, and their lysis, or breakdown, causes the symptoms of CAD.

How rituximab plus bendamustine work

Rituximab is a first-line therapy for CAD. It has proven effective in alleviating symptoms as a stand-alone treatment.

A monoclonal (or single) antibody, Rituximab is designed to target B-cells, the immune cells that produce autoantibodies such as cold-agglutinins. Treatment with rituximab depletes the B-cells and prevents the excessive production of these harmful autoantibodies.

Bendamustine is a chemotherapeutic agent that interferes with DNA synthesis and prevents the proliferation of cells, including immune cells.

For patients who do not respond to management methods like warming, the combination of these two therapies to slow down the immune system may be useful.

Rituximab plus bendamustine in clinical trials

A prospective Phase 2 study (NCT02689986) assessed the safety and efficacy of rituximab plus bendamustine combination therapy in 45 eligible patients (20 men and 25 women) with CAD. Some participants (14) previously received rituximab or a combination of rituximab plus fludarabine.

The results showed that 32 patients responded to the treatment.  Of these, 19 achieved complete response while 14 had some level of partial response. Among those who were previously treated, 50% showed complete clearance.

Other information

Rituximab is a therapy approved by the U.S. Food and Drug Administration for non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus vulgaris. It is marketed under the brand name Rituxan in the U.S. and as MabThera in Europe.


Last Updated: Aug. 15, 2019.


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