myelodysplastic syndrome

You know, I've now treated hundreds of patients with PROT.

And I've seen a rate of MDS and even AML of about 1% to 2%.

And those cases are so memorable, right? Because they're exactly what you and I fear the most.

You don't want to take someone who has a more indolent disease biology and give them a more aggressive one.

In my practice, PRRT, I think, is a very commonly used tool, usually in a second-line state, for most of our midguts and gap nets in general.

But there are always times where I feel in a younger patient, in a very low-volume disease, where I'm worried about all these long-term problems.

You know, myelotoxic disease, MDS risk, and for that matter, even long-term renal safeties.

Should I expose somebody with systemic radiation if we can have other tools, especially with new age targeted therapies and even some chemotherapies that can stabilize the disease for a bit? But at the same time, if I have a patient with a lot of extrahepatic disease, which is lighting up very brightly on dotatate pad, has high SSTR uptake, PRRT is a very relatively low toxicity, at least for acute toxicity, well tolerated and low burden.

when and how and making yourself available.

Yeah, and I have a brother right now that has had MDS, which is a similar type of blood cancer.

And we had been a little bit at odds up until his diagnosis, and now we're very close.

And About

In separate lines, we were looking at other dependencies in BPDCN cells, and it turns out that BPDCN is also uniformly and very sensitive to BCL2 inhibition with a drug like venetoclax more so than aml sort of across the board more like it is in cll where it's quite sensitive to levels of venetoclax that are achieved in patients that was the genesis of combining these three drugs into a triplet regimen it also helps of course that we are leukemia doctors who mostly take care of these patients and we're very familiar with giving venetoclax and azacytidine as we do for patients now as an approved regimen for aml That was the reason that we brought these together into a triplet.

Finally, I'll say that we did a phase 1b study that preceded this paper published in 2024, where we did dose escalation first of the Tegraxifus azacitidine doublet combination, and then adding in the triplet Tegraxifus azacitidine venetoclax in patients with AML and high-risk MDS.

That allowed us to come up with the recommended phase 2 dose that was used in this paper.

Can you summarize this phase two study design along with your major findings?

We have been studying the genomics of BPD-CN, and maybe as we get larger numbers of patients, we will be able to break down prognostic and predictive subgroups.

But in this, we really weren't able to.

But I do think it is worth pointing out what you mentioned is that 20 to 30% of patients, and that's exactly what we saw in this study with BPD-CN, have either a pre-existing or a concomitant other heme malignancy, most frequently myeloid disorders like MDS or CMML.

And it's important that we don't exclude those patients from trials.

Well, on Scott's show, we briefly interacted, and you said my angels were going to take care of me.

I have MDS.

It's a bone cancer.

And in between then and now, I applied at UCSF bone marrow, got turned down because of my age, 82.

Well, on Scott's show, we briefly interacted, and you said my angels were going to take care of me.

I have MDS.

It's a bone cancer.

And in between then and now, I applied at UCSF bone marrow, got turned down because of my age, 82.