EHA 2019 | MRD and CR impact survival in gilteritinib-treated FLT3+ R/R AML

So those are updated results from the CHRYSALIS study, where we looked at measurable…. And the CHRYSALIS study was the dose-finding study for gilteritinib with FLT3 mutant patients. That showed that

So those are updated results from the CHRYSALIS study, where we looked at measurable…. And the CHRYSALIS study was the dose-finding study for gilteritinib with FLT3 mutant patients. That showed that gilteritinib induces a very nice response rate in these patients, 50%.

We used a novel assay in which the DNA sample is first amplified by PCR and then chopped up and put on an Illumina platform, analyzed by next generation sequencing. And that is what we call our FLT3-ITD MRD assay. And it’s highly sensitive, provided you feed enough DNA into it, to represent enough cells. And it actually gets down to one cell in better than 10,000 so below 10 to the minus four.

And so we found that patients who had a response… First of all, any patient, if you just stratified them by MRD level, survival was linked to the amount of tumor in this assay. So low levels of MRD versus higher levels of MRD did better.

But we looked specifically at the patients who had achieved a response, a CRC, call it a CRI, CR whatever, with gilteritinib and asked, okay, now take the patients in that group and ask how did the ones who were below, we’ll just say 10 to the minus four as a sort of an arbitrary level. If they’re below 10 to the minus four we’re going to call them MRD negative. They aren’t really, we can actually detect something, but they’re below that threshold.

And again, the survival curves split very nicely. If you had lower MRD, you did better. So the gilteritinib responses are acting like a proper response, A. B, we can use MRD, it’s moving the field forward to using MRD as our response marker, not survival or whatever this CR thing is. And that’s really what we’re trying to do with this.