CD38

So tell us about this drug Sarclisa and what does the FDA approval of the new variety of this called Sarclisa Acena add for patients and healthcare providers?

So, Dr. Seichert, sarclisa or esotuximab belongs to an important class of drugs in myeloma, which is called CD38 monoclonal antibodies.

There is one other drug available called dartumumab or Darzalex, and sarclisa or esotuximab is another agent available here.

These are very important drugs.

And then we have like a very severe case of like chronic fatigue people and autoimmune disease where they have SASP, senescent associated secretory phenotype.

So what the heck does that mean? That means the senescent cell produces an inflammatory cytokine, well, multiple ones, but mainly interleukin-6, which then upregulates CD38.

That's the hungry, hungry hippo to your NAD, meaning it's going to overly consume your NAD.

It will also increase NNMT levels.

You just gotta take care of the inflammatory senescent cell situation first.

Then you can utilize NAD because some people, here is the ironic paradox or whatever, some people of severe diseases need NAD to heal, but you have to regulate the enzymes.

You have to regulate NNMT and CD38, and you have to reduce the inflammation.

before you can bring in NAD for yourself to heal.

It's a consumption issue.

As we accumulate those senescent zombie cells we talked about earlier, the resulting chronic inflammation upregulates an enzyme called CD38.

And what does CD38 do?

it aggressively consumes NAD plus battery.

It eats it up.

Well, it's a combination of decreased synthesis and increased consumption.

But the sources point to a massive aggressive driver of this decline.

The upregulation of an enzyme called CD38.

And it just chews up NAD.

So CD38 levels going up means your NAD levels are going down.

So it does make sense to also address the CD38s eating up NAD because you don't want too much of this enzyme in your system.

Well, let me ask you a question.

So why does that enzyme increase production? Is there a reason if that is what's eating? I'm thinking of it as, for instance, like the difference between free testosterone and uh, actual testosterone production, right? Is because you're, you're looking at like a, like a, a sex hormone binding globulin, right? Like, so I'm talking now about SHBG and how levels of SHBG are actually eating up testosterone.

But it's coming out from somewhere else.

But the more... holes that you have, the more energy goes into fixing the problem, kind of what we were talking about, like the sick care, like, you know, the leakier gut you have, the more energy goes into fighting the inflammation, and now starts the vicious cycle, that more of your energy goes into fighting the bacteria, the bad guys, instead of, like, you know, recovering or sending the energy somewhere else.

So CD38, that enzyme I mentioned, is part of it.

So again, PARPs run off of NAD plus, so we need the NAD plus to have this DNA damage repair crew operate and do what it's going to do.

And then we have CD38 basically that sits on immune cells.

It destroys NAD plus and its precursors.

And again, the CD38 is going to climb steadily with age.

And also the more inflamed we are, the more it's going to express and then ultimately chew up the NAD plus.

So again, in addition to it doing the things it's going to do in the body, it also kind of serves as a fuel source, as an enzyme for these other things that consume NAD plus.

It's not forgetting how to make it.

So it's just running out of the ability to make it and it's burning through it faster.

He was here.

We talked all about the NMN, um, the CD38-

Yeah

... part of the conversation, which is, like, this NAD shredder, and it goes up as you age, so having different resveratrol polyphenols to bring down CD38 and then introduce the precursor, the NMN, to turn into NAD.

The CAP's accreditation program hits a milestone.

A webinar on how to advocate for pathology and a new proficiency testing program on anti-CD38 interference.

These stories and more coming up next.

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We've been telling you about the CAP's new proficiency testing programs now available for order for 2027 delivery.

Today, we focus on the anti-CD38 interference antibody screen.

Anti-CD38 drugs are used to treat blood cancers but can cause interference with some laboratory tests.

But at the end of the day, quad therapy still remains the current standard of care in frontline setting.

And then we continue on with our anti-CD38 and len-based maintenance.

Though for standard risk, after the endurance trial, two years of len maintenance is rather sufficient.

Ajay, to get us started, what data do we have for upfront quad therapy, and what can patients expect with this treatment in frontline settings?

So I...

When I speak to patients about dara, I explain it's a monoclonal antibody that targets CD38.

It's relatively well-tolerated, any of the anti-CD38, dara or isa.

They're well-tolerated.