Fw: Will Targeted Therapies Work for CLL? lymphoma

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Subject: Will Targeted Therapies Work for CLL? lymphoma

Will Targeted Therapies Work for CLL?

BRET SCOTT: I'm Bret in Orlando, Florida, site of this year's meeting of the American Society of Hematology. Monoclonal antibody therapies that directly attack cancer cells are a hot topic in medicine. At this year's meeting, several research presentations focused on the use of these therapies for chronic lymphocytic leukemia, or CLL. I sat down with some of the experts to learn more about this development. Dr. Rai, is Rituxan improving on traditional treatments for CLL? And if so, how? KANTI RAI, MD: Rituxan is indeed improving on traditional treatment, if one considers today in year 2001 that fludarabine is the standard treatment for CLL. We get just so much of what we call "remission rate" with fludarabine. And we find that when we add Rituxan to fludarabine, the remission rate is practically doubled. BRET SCOTT: Dr. Connors, will Rituxan be used differently to treat CLL compared with NHL? I'm thinking schedule and dose here. JOSEPH M. CONNORS, MD, FRCPC: ! I would expect that it will. The schedule that works for a tumor-like lymphoma, where the cells are settled in one place in the body may well be different from the schedule that works best for a leukemia, where the malignant cells circulate around in the bloodstream. So I think we may expect different doses, different schedules and even different lengths or durations of treatment. BRET SCOTT: Dr. Rai, any thoughts? KANTI RAI, MD: Rituxan in lymphoma is given once a week for several weeks. Four weeks, six weeks, eight weeks. And it is quite effective in those patients. But when you give Rituxan in the same manner to a person with CLL, it just does not have much activity. However, when you give Rituxan in combination with other standard chemotherapy drugs and, instead of giving it on a weekly basis, you give it once a month, the combination is a blockbuster. BRET SCOTT: Dr. Rai, several treatment options for CLL using Rituxan were discussed ! at this meeting. Can you briefly explain the main options? KANTI RAI, MD: Well, let me explain to you that the introduction of Rituxan in CLL is relatively recent happening. So we cannot claim that we know everything as to how to use Rituxan in the most effective manner for our patients with CLL. Therefore there are lots of combinations and permutations being tried with an objective of finding out what works best for what group of patients. BRET SCOTT: Dr. Connors, how will Rituxan be used in treating younger patients versus older patients with CLL? JOSEPH M. CONNORS, MD, FRCPC: I'm going to turn that question around a little bit, because one of the real virtues of antibody treatment -- monoclonal antibody treatment is the ability to treat older patients with it, when the toxic effects of other kinds of treatments may prevent you from doing so. So I think that we will find that rituximab is used in older patients that we might not have been able to otherwise treat well. But ! to return to younger patients, I expect it to be combined with other still fairly intensive treatments in attempts to get rid of all of the leukemia completely. But that is moving to an era where we actually attempt to cure the disease, as opposed to control it as we might have in the past. BRET SCOTT: Dr. Connors, Campath is another monoclonal used to treat CLL. How does it differ from Rituxan and how is it used? JOSEPH M. CONNORS, MD, FRCPC: The difference is the target. The monoclonal antibody in question is always directed at a specific surface characteristic or a small bump as I describe it on the surface of the cells. Rituximab is targeted at one that has the technical name of CD20 and is shared across many different kinds of lymphocytes, but closely restricted to lymphocytes. Campath is directed at a different surface characteristic or bump that is shared across not only lymphocytes, but other different types of blood cells. And so, although restricted to a small numb! er of cells, the Campath antibody does have effects on some of the cells we aren't targeting it towards, and we have to allow for that affect and the possible side effects that may come with it. BRET SCOTT: And Dr. Rai, what about side effects? KANTI RAI, MD: Well, side effects with the rituximab are somewhat of a lesser magnitude than side effects with Campath. Campath is an antibody which kills all lymphocytes, whether they are B-cells or T-cells. In CLL, as you perhaps know, that it is the B-cells that we are trying to kill, because those are the malignant cells. But the T-cells we don't have to kill, but Campath does not discriminate between Bs and Ts, so they kill all the cells and thereby renders a person's immune system much more vulnerable to opportunistic infections, such as pneumonias and blood infections. As far as other immediate effects or concerns, both the drugs -- Campath and Rituxan -- do cause some degree of shaking, chills and fever and drop in blood press! ure, when a body, when a patient's body first is exposed to either one of these drugs. But with continued use, the body gets adjusted to this and subsequent use that problem is reduced markedly. BRET SCOTT: Dr. Connors, does adding chemotherapy to these targeted approaches increase the side effects? JOSEPH M. CONNORS, MD, FRCPC: Well, it's an exciting area of research to add these together, because the antibodies and the chemotherapy can interact with each other and boost the effectiveness of each other. As we do this, we monitor patients carefully to see if any new or unexpected side effects or toxicity develops. So far, that hasn't been a problem. In large part because the antibodies have different kinds of side effects than traditional chemotherapy, and patients can actually tolerate the combination of these two side effects without them adding together. BRET SCOTT: Dr. Rai, what is the ultimate goal of these targeted approaches? Can they cure CLL? KANTI RAI, MD: Well, th! at is our aim, and that is our objective, but I would be overstating the case that these combinations will get us to that endpoint. But, in my view, the combination of both of these antibodies along with chemotherapy, in some form or another -- as time goes on, we will find out -- will aid us in significantly better overall treatment for CLL patients than we have been able to deliver to those patients for the last three or four decades. BRET SCOTT: Dr. Connors, your closing thoughts? JOSEPH M. CONNORS, MD, FRCPC: We continue to work, I think, in an increasingly exciting era of the treatment of cancers. Understanding the basic biology, identifying specific targets that cancer cells uniquely express and developing the therapeutic -- the treatment tools to go after these cancer cells with these specifically targeted treatments is a sea change compared to the first twenty years I spent in this field and adds to the excitement and the anticipation that these treatments will be gr! adually turning into effective curative ways of getting rid of the cancer. BRET SCOTT: Dr. Connors, Dr. Rai. gigi http://www.healthology.com/webcast_transcript.asp?f=leukemia & b=abcnews & c=lymphoma_rituxanash3 & transcript=yes