Linda Liau’s Seattle Science presentation had been taken down - pretty quickly as a matter of fact - which she gave almost two years ago. But it has recently been posted again. Some of the things that she had said at the time didn’t really pop out to me then, but the pop out for me now. I think I was focused on the entire pseudo progression topic that she spent a great deal of time on, and so hadn’t focused on some of her other statements. And then the video was pulled, and I couldn’t revisit it until now.
For instance, she mentions 3 year survival at least three times in this presentation.
At 11:15
But I think the true benefit of immunotherapy is really out here. It’s really the tail end of the curve. Cause what a lot of us are seeing is that there are twenty, to almost even thirty, forty percent of patients that do live significantly longer. Meaning three years or more with immunotherapy.
At 12:50:
But also there is a need for relevant endpoints. You know, median survival, overall survival at one year, or even two years, is really… may not be the meaningful endpoint for these trials. It’s really that long term tail end. The hazard ratio at three years or four years is really what we should be computing for these trials.
At 41:38:
So these patients, because they were off trial, we were able to analyze their data early, and this is essentially what that data shows. Of the 25 patients that were pseudo progressors or possibly pseudo progressors, uh ten of them are, err, still alive over three years. They’ve progressed.. uh… they haven’t had any… not even alive… they actually… you know, most of these haven’t even had progression.
She also made this statement, that reminds me of Dr. Bosch’s 2018 ASCO comment regarding waiting for three years.
Linda Liau, December 2016
11:35
So the problem with the current design for FDA approval is that you submit a trial. The endpoints are difference, for instance, in overall survival, or median survival. You see some difference, and if you’re lucky, they’re statistically significant. But you’re not really capturing this tail end.
But in reality, when you treat patients, if you give them the option, you tell them if you can live three more months with this therapy, versus, you have a twenty to thirty-five percent chance of living five more years, most patients would actually opt for that thirty percent chance of living five more years than okay, I’ll do this and I’ll give you three more months.
Marnix Bosch, 2018 ASCO
So for instance, if you were in the trial and survived for that 24 months or more, your life expectancy is about 38 months. In fact, it’s 38.6 months. If you were operated on 30 months before we did the analysis and you are alive, 67 patients at the point of analysis (MARCH 2017), your life expectancy has increased. But look, you have greater potential here. But if you’re six months longer in that trial, suddenly your survival time, your expected survival time, the [??] term is kaplan meier-derived survival estimate, my translation is expected survival time, or survival expectancy, goes from 46.5 months to 88.2 months.
So you'll note that both statements come down to how DCVax as a treatment option could be presented to a patient.
I was able to transcribe the whole presentation this time (in case it gets pulled again) so I’ll post that tomorrow. In the meantime, I’ll end this with two more quotes that she made that I had want to draw your attention to.
LL makes that point that when they went back and looked at all the patients in their phase one/two trials, they found that those who did best were those that usually do worst… the mesenchymal subgroup.
22:13:
Interestingly, the patients who actually saw the most benefit from immunotherapy was in the mesenchymal subgroup. And that’s actually the poorer [performing] subgroup. Those are the ones that are IDH1 wild type, MGMT not methylated. Well methylated or nonmethylated, it was actually in both populations. But those are the ones who typically have, you know, a median survival of about 14 to 16 months. So in that group, the vaccine actually did seem to show a significant difference. And actually, all our long term survivors were in the mesenchymal subgroup.
So there is something about that particular subgroup that you know, I think is, you know, inducing a perhaps better immune response for these patients. And that’s kind of what we’ve been studying, you know, for the last five or six years now.
But you’ll also notice that when LL discusses MGMT methylated and unmethylated above, she first indicates that the IDH1 wild-type is found in MGMT unmethylated, which is what I think most of us thought.
But then she changes that observation to indicate that IDH1 wild-type is actually present in both populations. I thought that was worth noting - that it was found in both MGMT plus and minus. I do wonder how many of that group of 100 longer living survivors from the interim data with a mOS of 40.5 months will turn out to be IDH1 wild-type.
