ASCO 2010: Treating CML

Dr. Sonali Smith discusses the newest developments in the treatment of CML.

Selma R. Schimmel, Founder & CEO, Vital Options International: I’m very excited to be able to talk about some of the fantastic data supporting our CML patients.

Sonali Smith, MD, Assoc. Professor of Med., University of Chicago Med. Center: Chronic myelogenous leukemia, I think, is really the paradigm or prototype disease where we have this concept of bench to bedside. So in other words, about forty years ago we understood that there was a molecular switch that turned on an abnormal protein and we call that protein a tyrosine kinase.

Fast forward to about a decade ago, a very unique compound called imatinib, which has the trade name, Gleevec, was developed for CML. And the way that Gleevec worked was very unique compared to chemotherapy. As opposed to chemotherapy, which tends to be very non-specific and kills normal and abnormal cells, the imatinib really hones in on that defect in that cancer cell. And this really changed how patients with CML do. It went from being a disease where everyone got chemotherapy and if they were lucky enough they would go through an allogeneic transplant, to now taking a tablet everyday and really changed it into really a chronic disease.

Selma R. Schimmel: And it was at another ASCO, I don’t know exactly how many years ago, but I remember it was in San Francisco, and the buzz at that ASCO, because of Gleevec, it was the talk at that year’s ASCO.

Sonali Smith: And really, rightly so, I mean the life for patients pre-Gleevec and post-Gleevec or post-targeted therapy is a big difference; it really helped. The reason, I think, the study that’s been presented at this meeting is important, though, is that although Gleevec helps the vast majority of patients with CML, we have some remaining issues.

One is that not everybody responds to Gleevec or they stop responding and there are other patients who can’t tolerate Gleevec. And so there have been what we call second-generation tyrosine kinase inhibitors developed to help fill that gap. And for patients who progress or their disease stops responding to the gleevec, they have options, which is very important.

The study presented at this year’s ASCO looked at those second generation inhibitors, these newer drugs that target the same protein as the Gleevec, but seem to be more potent, and tested it in patients who had never been treated. So now there are 500+ patients that were enrolled in this study, they have never been treated, they all have CML, they all have this abnormality, this Philadelphia chromosome, and then half got the Gleevec and half got dasatinib, which has a trade name Sprycel. And this is early data, I want to really caution that and…

Selma R. Schimmel: What phase is this trial?

Sonali Smith: This is a phase three trial and they, the investigators looked at how many patients were able to have their Philadelphia chromosome eliminated with either the imatinib or the gleevec arm or the dasatinib/Sprycel arm. And with their twelve-month data, there was a doubling of the percentage of patients who had their chromosomes turned to normal, and the name for that is complete cytogenetic response. They also looked to see if the actual protein product disappeared and the name for that is major molecular response. And again they found that the patients who received the dasatinib were twice as likely to have their protein disappear.

Selma R. Schimmel: When you talked about some of the issues with patients having difficulty coping with perhaps the side effects… what were some of the side effects of the gleevec that were difficult as compared to the side effects with the current compound?

Sonali Smith: So the side effects are not generally life threatening, they’re more annoying and irritating and tend to affect quality of life. So there is some nausea, there is some swelling that can occur either around the eyes or around the legs, and there is fatigue. You know, these are not things that would land somebody in the hospital, but certainly for a tablet you have to take every day to stay alive, they were bothersome to enough patients. And it’s not that dasatinib doesn’t cause these side effects, but it caused it less often.

Selma R. Schimmel: It’s also an oral therapy.

Sonali Smith: It is also an oral therapy, correct.

Selma R. Schimmel: Do you have to deal with issues of patients adhering to their therapy?

Sonali Smith: Yes, I think you know, adherence is always an issue. There are patient diaries that help people remember what they’re supposed to take and when they’re supposed to take it. I do think that within the CML community, within patients who have to take these tablets, it’s made such a difference that I do think that adherence is probably better than let’s say with an anti-blood pressure medication, you know, I do think that people take it. But that’s always a valid concern.

Selma R. Schimmel: And what is the course of the therapy?

Sonali Smith: So it’s just one tablet a day, it’s 100mg per day if you’re on the dasatinib and 400mg per day if you’re on the imatinib.

Selma R. Schimmel: And for how long?

Sonali Smith: Well, now here is the challenge- it’s really for the remainder of that person’s life. We have no data with any of these tyrosine kinase inhibitors that you can stop therapy. You know, most people who stop will have their disease come back.

The other issue is that there is also a risk that, you know chronic myelogenous leukemia actually has three phases and most patients have… so it’s chronic phase, then there is an acute phase and then there is a blast-crisis phase. And these oral agents all are indicated right now, or imatinib is FDA-approved for patients in the chronic phase. There is a small risk that patients who aren’t responding will transform into one of the more aggressive phases and that’s something to keep in mind, you know, with some of the new drugs that are coming out. It seems very, very early that dasatinib may be a little bit better than the Gleevec at the risk of transformation, but it is very early follow up, it’s only twelve months so far. So we have a long ways to go before we really know the place of some of the newer agents.

[End of video]