SLIDES & TRANSCRIPTS
Monday, May 12, 2003

Allogeneic and autologous SCT

Jacob M. Rowe, M.D.

just an outline of the trial, jointly conducted between MRC and Britain and ECOG.

Patients get standard reduction and then, irrespective of the risk group, if they have a donor under 50 years of age, they get assigned to an allograft. If it is a Ph positive, they can also get a MEC.

Otherwise, they get randomized between an autograft and a conventional consolidation maintenance therapy, done early.

The data I am going to show you are from these early assignments, an intent to treat analysis. All patients then go on to get high dose methotrexate as intensification, following which they get the treatment to which they have been assigned.

TOP

The current update is looking at seven years. This has been done, you can see almost 1,400. The data I show you is 1,389, 37 percent at seven years, which is with respect to the entire study population.

What I want to show you is that there are 250 patients who are out at five years, and most of the data that I am going to show you is based on five years.

TOP

I am going to be splitting this and I am going to be focusing on Ph negative. Tony will focus on the Ph positives.

If you look, out of the 1,441 patients, there are almost 1,000 who are Ph negative. The overall CR is 91 percent, 93 percent for Ph negative, 83 percent for Ph positive.

If you go down -- this is where we get our intent to treat analysis.

We get comparative data. We have 289 patients who were assigned to an allograft, and the total number of patients who were planned and allografts, among the Ph negative, is 214, altogether 313 randomized.

Since we want to make this comparable, we are looking at the less than 50. So, we are really comparing this 214 and 280, because both of these are the same age group.

TOP

This is representing the data. Let's just skip on. We used standard criteria between the high risk and standard risk.

TOP

This is just to show you, the next slide is really the bottom line of the data we have to date, and here I want you to look at it.

TOP

If we look again, these are patients who, this is by intent to treat analysis, patients under 50, the allogeneic group versus the randomized group.

We compare the overall event free survival, overall survival, relapse rate, all highly significant. If we then split it out by standard risk, by definition, standard risk patients are all young ones. You have to be less tan 35. Otherwise, automatically it went quickly into CR and didn't have a high white count.

You look at the event-free survival comparing the allogeneics versus the randomized overall survival and, except for one number here, which is the overall survival -- although there is a difference here, it doesn't quite make statistical significance -- but clearly, very marked benefit for the allogeneic group in an up front comparison.
Just briefly, I will show you one or two curves.

TOP

This is the curve looking at the overall survival, Ph negative, between the allo PMT and the randomized patients.

TOP

This is the event-free survival, even more impressive. Next one. Let's just move through these just because I want to finish.

TOP

Really, the most impressive part, really, has been the vast difference between the relapse rate, what Steve showed earlier.

You will see that in some of the favorable groups, in the standard risk, it is as low as 15 or 17 percent. The graft versus leukemia, for allogeneic transplants in first CR is extraordinarily impressive.

TOP

This one is just to show you, because this is the controversial area, assigning patients with standard risk. These are young patients.

You can see, if you look at the event free survival, Ph negative, standard risk, young patients, and the difference between allogeneic and randomized patients.

TOP

This is just to show you, here we get into tiny little groups. Even when we look -- and these are controversial groups -- but even if we tried to pick up a group that you may say would be the best, standard risk, young ones, T lineage, now the numbers get much smaller. There isn't a hint that, when we tease out any single group that, in fact, allogeneic transplant doesn't maintain its advantage at five years.

Of course, these are randomized. The study is ongoing. So, I can't tell you about autologous transplants, but I have it from the statisticians that they are sufficiently similar that it wouldn't make a difference.

What I am doing, I am taking the randomized group here, but it wouldn't make a difference whether we just pulled out autologous transplants, although the precise studies are remaining open. Now, Tony will continue with the PH positive.

TOP