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Rituxan: Not Just for Cancer?

Posted Aug 24 2008 1:49pm
BRETT SCOTT: I'm Brett Scott in Orlando, Florida, site of this year's meeting of the American Society of Hematology. Rituxan is well known to oncologists here as a treatment for non-Hodgkin's lymphoma. But this year several presenters discussed how it's being used to treat blood disorders other than cancer. During the conference I sat down with one expert to discuss this exciting area of research.

Dr. Kessler, we know that monoclonal antibody therapy, particularly Rituxan, has been successful in treating several kinds of blood cancers. Can you explain why?

CRAIG M. KESSLER, MD: I think the basic principle over here for the use of Rituximab is that it is an antibody which is directed against other types of antigens or proteins on the surface of lymphocytes, a type of white cell in the circulation. These particular white cells are the white cells that are responsible for producing certain types of blood cell malignancies called lymphomas and chronic lymphocytic leukemias. The characteristic protein on their surface with the target of the antibody directed against that surface, will allow that cell to be bound by the antibody and then the antibody will destroy that malignant cell.

BRETT SCOTT: At this meeting there are several presentations on the use of Rituxan for ITP or TTP. Can you comment on the rationale behind this and the success?

CRAIG M. KESSLER, MD: ITP is immune thrombocytopenic purpura. TTP is thrombotic cytopenic purpura. These are diseases of the immune system which both result in a very dramatic decrease in the platelet count in the bloodstream. And when these platelet counts decrease then the patient is at increased risk for bleeding into organs, brain, GI tract, bladder, etc., and it can cause very severe disease. Knowing that the immune system is altered in these individuals and that it's the proliferation of these abnormal lymphocytes that are associated with the development of the disease, then the use of Rituximab again can be used to target those specific abnormal lymphocytes in the bloodstream and in the bone marrow and thereby eradicate this population of cells responsible for producing the disease.

BRETT SCOTT: There are also presentations this weekend on the use of Rituxan for certain forms of anemia and Factor 8 deficiency. Is the rationale for use in these conditions the same as ITP or TTP?

CRAIG M. KESSLER, MD: Similar. But let me explain to you what these diseases are so that you can understand why there's a similar rationale. Individuals who have a specific type of anemia which is called autoimmune hemolytic anemia are anemic by virtue of the fact that their immune system produces an abnormal antibody which coats those red cells. And then the red cells are taken up into the immune system and destroyed, very similar to the way that the platelets in ITP are taken up into the immune system after they're coated by antibody. This is the rationale, again, for eliminating the clone of lymphocytes that are responsible for producing that antibody.

From the hemophiliac aspect, this is a very special type of hemophilia that we're talking about. This is called acquired hemophilia. These are individuals who have never had any bleeding problems in their past histories and all of a sudden present with sever life-threatening types of bleeding episodes. Again, the ideology of that bleeding disorder is that antibodies form against their blood clotting factor, and when these antibodies form against the blood clotting factor it eliminates that clotting factor from the circulation and consequently these individuals essentially look like severe hemophilia patients.

BRETT SCOTT: You just gave a presentation on the role of monoclonal antibody therapy for autoimmune blood disorders. Can you briefly review the main points?

CRAIG M. KESSLER, MD: My talk today essentially reviewed the anecdotal results of a significantly rising number of patients who have received Rituximab for treatment of their autoimmune hematologic diseases. All of these diseases in some way are produced by the production of abnormal antibodies by the immune system. And the ability to use Rituximab in a way to modulate the production of those abnormal cells and to eradicate those cells, I think, has dramatic promise for the future treatment of these disorders. It's too early, however, to state that all patients and all of these abnormalities will be universally treated successfully with Rituximab.

BRETT SCOTT: Is there a difference in how you prescribe Rituxan in benign versus malignant disease?

CRAIG M. KESSLER, MD: In the small number of individuals who have received Rituximab for these benign hematologic abnormalities, the traditional dosing schedule which has also been used for indolent lymphomas has been used. The side effects appear to be equal. The question is whether or not a modification of the dosing regimens is going to be necessary to make these diseases more amenable to treatment with Rituximab and only time will tell on that.

BRETT SCOTT: Apart from Rituxan, are there other monoclonals in use or in development for these blood disorders?

CRAIG M. KESSLER, MD: There are other monoclonal antibodies that are evolving in their use in both benign and indolent lymphoma diseases. And I think that it's, again, too early to say whether or not those other antibodies, such as Campath, for instance, would be able to work as well or less well than Rituximab. Again, we're very early into the exploration of the usefulness of these monoclonal antibodies in benign hematologic disorders.

BRETT SCOTT: Doctor, any final thoughts for viewers watching this webcast?

CRAIG M. KESSLER, MD: I believe that the take-home message for this webcast related to the use of Rituximab is that this is a very powerful tool that we are now learning how to use properly, and if it has half of the success rate in benign diseases as it has in the malignant lymphomas, then I think that all of us, as physicians and the patients themselves, will certainly have something new to be able to use as a new promise for the treatment of these very difficult diseases.

BRETT SCOTT: Dr. Kessler, thank you for your time. Enjoy the meeting.

CRAIG M. KESSLER, MD: Thank you.

BRETT SCOTT: And thank you for watching. I'm Brett Scott.

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