So walk us through that and, and let's start with residency.

Fantastic question.

Yeah.

I mean...

You can start with a residency.

You can also even go back to med school.

I mean, I think the first thing you wanna do when you are interested in clinical research is do clinical research.

Getting a little bit into more of the nitty-gritty, what does your day-to-day look like compared to someone who maybe has more of a purely clinical practice?

So walk us through that and, and let's start with residency.

Fantastic question.

Yeah, I mean You can start with a residency.

You can also even go back to med school.

I mean, I think the first thing you wanna do when you are interested in clinical research is do clinical research.

And one of the great things about clinical research is any med student can do it, any resident can do it.

You just express interest to a mentor that you know is doing clinical research, and by the way, that mentor can be a fellow in the field that you're interested in.

Getting a little bit into more of the nitty-gritty, what does your day-to-day look like compared to someone who maybe has more of a purely clinical practice?

I'd be curious how often the investigators see patients with not just ecchymosis or mucosal bleed or nosebleeds, but really true gastrointestinal CNS bleeding in ITP.

So this is obviously a harrowing case, right, of this patient with platelet count of one, with GI bleeding, with brain bleeding.

You want to do everything you can, and I totally agree with giving him dexamethasone to try to increase the count as quickly as possible.

Presumably IVIG would be used as well, right, in a circumstance like this because that will give us our fastest response typically within 24 to 48 hours.

This guy's ITP was not easy in his early 30s, which is a little atypical.

But nevertheless, escalating doses of vermiplestim, gave rituximab, also gave cyclophosphamide and vincristine.

Vincristine is – a, uh, it's not a bad rescue medication, right? We don't reach for it very often because we don't want to give people neuropathy and, you know, uh, uh, long-term complications, but it does work in about 70% of patients and it raises the platelet count relatively quickly.

I would love to know where that data stands and if there's still any concern for long-term toxicity with these medications, particularly concerns for either myelofibrosis or myeloproliferative neoplasms.

You want to talk about that?

Absolutely.

FAHIT-3 was a phase two study that looked at enolumab in patients that had received many prior treatments and using enolumab as a single agent treatment.

Patients who were on stable doses of corticosteroids or thrombopoietin receptor agonists could continue those at a stable dose throughout the study, but the intervention was just enolumab and no placebo arm as a single arm study.

And so this The patients in the study were heavily relapsed refractory, among the most relapsed refractory of any ITP study that's ever been done.

So a difficult population.

And they received four infusions of unalimab at 9 milligram per kilogram.

You want to talk a little bit about that?

So let's talk about the other major development and what seems to be a new era in ITP management, the BTK inhibitor rilzabrutinib and new data presented at the ASH meeting on the Luna 3 study of this agent.

Rilzabrutinib is a later generation, some would say third generation, BTK inhibitor.

It is very targeted for the BTK with fewer off-target kinases impacted significantly than earlier agents like abrutinib, rilzabrutinib, zanubrutinib.

And the main purpose of rilzabrutinib development is actually in autoimmune disease.

And so it was first developed in ITP.

It's currently being evaluated in warm autoimmune hemolytic anemia.

Why is it beneficial for it to be more targeted? Well, we recognize right with many of the earlier BTK inhibitors that they inhibit platelet function and they cause bleeding.

So let's hear some more about rilzabrutinib and the data that was presented at ASH in the LUNA3 trial.

Any recommendations for a 65-year-old woman with ITP who suffered an MI? with a platelet count of 14,000, had stents placed, and cardiology wants to put the patient on DAPT if feasible.

Yeah, yeah.

All right, so first we'll talk about splenectomy, and I will challenge your question about unfair malignment.

I think that, by and large, I like spleens.

I want to keep spleens in bodies as much as I can.

There is a place for splenectomy and ITP.

I think that is true.

Let's talk about the data.