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Expanding the Use of Rituxan in NHL Treatment

Posted Aug 24 2008 1:49pm
BRETT SCOTT: I'm Brett Scott in Orlando, Florida, where researchers have converged for the meeting of the American Society of Hematology. In recent years, the drug Rituxan has been a popular topic among attendants. It's a monoclonal antibody approved for several types of non-Hodgkin's lymphoma. But this year, many presentations are addressing its use in other types of NHL. I sat down with some experts to find out more.

Let's start with the basics, Dr. Press. What is Rituxan currently approved for?

OLIVER PRESS, MD: In this country, Rituxan is currently approved for the treatment of patients with relapsed indolent lymphomas including those with bulky disease and those which have recurred after initial therapy.

BRETT SCOTT: Dr. Marcus, there are many types of NHL. Can you briefly describe the main ones and the main stages?

ROBERT MARCUS, MD: Well, that's a complex question which I'll try and simplify as much as I can. The majority of patients will fall into two main categories either diffuse large cell lymphoma which pursues an aggressive course untreated or follicular indolent lymphoma which pursues a comparatively nonaggressive course. In terms of staging, the classic staging supply a single group of glands, more than one group of glands which would be stages I and II. The disease on both sides of the diaphragm would be stage III and disseminated disease would be stage IV. There are other prognostic measures which can be used to assess the outcome of the patient.

BRETT SCOTT: Are these less common types of NHL traditionally more difficult to treat?

ROBERT MARCUS, MD: Not necessarily. Not by definition. But a certain subtype such as mantle cell lymphoma which are often quite resistant to treatment, but other rarer types such as small lymphocytic lymphomas aren't necessarily more difficult.

Lymphomas arising from T cells obviously aren't amenable to antibody therapy but aren't necessarily as a consequence more difficult to treat with chemotherapy.

BRETT SCOTT: Dr. Press, why is Rituxan being used in these different types of NHL?

OLIVER PRESS, MD: It's being used predominantly in lymphomas that express a lot of the CD20 antigen. There is a molecular target on the surface of these lymphomas which the antibody binds to and fortunately, about 85% of lymphomas express this target very well. Those lymphomas which don't -- predominantly T cells lymphomas aren't really amenable to therapy to Rituxan as is mentioned.

And other diseases such as chronic lymphocytic leukemia which express a small amount of CD20 can be treated with Rituxan, but it hasn't been as dramatic a success there as it has been with the lymphomas that express more of the antigen.

BRETT SCOTT: Let's take a couple of specific examples. Dr. Marcus, can you comment on the use of monoclonal antibodies to treat aggressive NHL? What is the recent news being communicated this weekend?

ROBERT MARCUS, MD: Well, the important trial is the French Cooperative trial published by the GELA Group which has compared CHOP chemotherapy (which has been standard treatment for now over 25 years) with the addition of rituximab to CHOP chemotherapy. Response rates have been increased by at least 15% and the event-free survival almost by 20%. So this may -- may represent, if confirmed, the most significant advance in the treatment of diffuse large cell lymphoma for 20 years.

I should add that it probably only applies to the group in which the trial was done -- that is the over 60s. But it may have major implication for the overall therapy for diffuse large cell lymphoma.

BRETT SCOTT: Dr. Press, what about relapsing or refractory lymphoma?

OLIVER PRESS, MD: Well, the initial trials were done predominantly with Rituxan in patients who had relapsed or were refractory to chemotherapy. And so that is a major indication for using Rituxan. Fortunately it doesn't appear that chemotherapy resistance necessarily corresponds to resistance to Rituxan therapy.

BRETT SCOTT: Dr. Marcus, are there any types of lymphoma where you are particularly excited about the potential use of monoclonal antibodies?

ROBERT MARCUS, MD: Yeah, there are some very interesting trials which are now ongoing, especially low-grade non-Hodgkin's lymphoma where Rituxan is being added to conventional chemotherapy to establish whether it has the same kind of benefit in low-grade disease as was seen possible -- or probable rather -- in high-grade disease.

There is a European trial which is comparing conventional chemotherapy plus or minus Rituxan and there are studies in the United States which are also examining Rituxan as adjunctive or maintenance therapy after conventional chemotherapy. If these trials prove positive, that again will be a very important and exciting advance.

BRETT SCOTT: Dr. Press, what about you?

OLIVER PRESS, MD: I would agree with Dr. Marcus on that issue. There is, I think, an important trial which has just begun in the United States that's looking at treatment of newly diagnosed patients with follicular lymphomas and comparing treatment with conventional CHOP chemotherapy alone to CHOP plus Rituxan to CHOP plus a radiolabeled antibody called Bexxar. And I think that trial hopefully will establish the roles of chemo alone vs. chemo plus antibodies vs. chemo plus radiolabeled antibodies.

BRETT SCOTT: Dr. Marcus, you just gave a presentation on front-line therapy using monoclonal antibodies. Can you briefly review your discussion?

ROBERT MARCUS, MD: At the moment, although there is some tantalizing early data, there is no actual proof that monoclonal antibodies make a major contribution in first-line treatment. And the trials that you've just referred to will hope to prove whether or not these agents are, indeed, valuable as adjunctive therapy, or consecutive therapy or maintenance treatment in these diseases.

BRETT SCOTT: Is it fair to say that these are hopeful times if you happen to be diagnosed with any type of lymphoma?

ROBERT MARCUS, MD: Not any kind of lymphoma. I think cure rates have steadily risen over the years although we haven't seen major incremental changes, as we did, for example, with the introduction of anthracyclines 25 years ago. We have seen steady improvements -- certainly in diffuse large cell lymphomas. I think improvements in follicular lymphoma have been much slower. It's quite possible that the addition of monoclonal antibodies to chemotherapy might indeed make that advance.

BRETT SCOTT: Dr. Press, in closing, do you have any particular message for viewers watching this webcast?

OLIVER PRESS, MD: In my opinion, this is a very exciting time both for researchers in the field of lymphomas and also for patients because there are many new exciting treatment options available now which weren't here 10 years ago. Besides Rituxan there is a whole family of other antibodies which is emerging -- Alemtuzumab, Campath, and a host of other antibodies. In addition there are radioactive antibodies which appear to be more potent than the unlabeled antibodies which are currently being reviewed by the Federal Drug Administration. And furthermore, there are antibody chemotherapy conjugates which are being developed. So I think that it's a very optimistic time from my point of view.

BRETT SCOTT: Dr. Marcus, final thoughts?

ROBERT MARCUS, MD: I would concur with that. I think they are exciting times. I think that monoclonal antibodies were first described 25 years ago. It's taken that length of time to bring them into clinical practice. I think they may make a major impact on the treatment of lymphoma.

BRETT SCOTT: Dr. Marcus, Dr. Press, thank you both for you insight. Enjoy the meeting. And thank you for watching. I'm Brett Scott.

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