Granulocyte colony-stimulating factor

So sometimes you have to give some

fertilizer, like some GCSF stimulating the white cells to come in.

Blood, platelets you might need a little bit, right? Some maintenance therapy on the back end.

We

In aphoresis collection, which is peripheral blood, you get, a lot of women tend to get central lines put in because our veins just aren't as large as nice, healthy adult males.

But you can also do it peripheral IV without a central line.

That requires shots of GCSF for about four days.

And then

Most of this happens in the first two or three cycles.

So when that happens, hold the drug, give G-CSF.

It settles down over time, but that's something to be aware of.

Infection signal is also there with both upper respiratory and lower respiratory tract infections, including severe infections being common, something to be aware of.

That speaks to how we think about folks who might be suitable for these types of agents.

We have to think very carefully about mitigation strategies, for example, GCSF to support neutrophils or use of a thrombopoietin memetic in order to support platelets if needed, and just being very vigilant for our patients.

Right now, these drugs are being studied in the trial setting where it's as homogenous a patient population as we can get.

Typically, on the healthier end, they're selected to have certain criteria for their blood counts or their functional status, etc.

You're right.

As we look at these pretreated patients, their bone marrow flexibility or tolerance to these kinds of medications is likely to be limited.

And we do need to be more careful and ready to jump in, as you mentioned, with GCSF for thrombopoietin agonists.

I think that's a really important point.

We see more gastrointestinal toxicity, diarrhea, nausea.

We see again in this trial more neutropenia, but, but this trial didn't, uh, consider everyone for prophylactic G-CSF, which is something we can possibly discuss later on when we go through, through those cases.

cases.So Melinda, kind of we seem like we're in a similar situation with ER-positive, HER2-negative disease where we have two Trop2 ADCs with s- similar data.

So here's a kind of a scenario they're putting out to you, and basically a patient who's HER2 low but PD-1 negative, BRCA wild type, metastatic disease.

She initiates, um, SG standard dosing, ten milligrams per kilogram IV on days one and eight of a twenty-one-day schedule.

You see her for cycle one, day eight, and her labs come back with a grade three neutropenia, ANC is seven hundred.

So you have to hold her, initiate G-CSF.

She has really prompt improvement, able to move forward with delayed day eight.

I may see them the following week to make sure that that's being effective, that I'm able to head off that neutropenia.

I'm not routinely adding IVIG unless they've had significant infectious complications in spite of GCSF administration.

Thanks.

Also, this population that was tested for dara exposed, how are you doing any management with regards to dara refractory, or they just were on dara and not completely refractory?

So this is not necessarily something that can be solved with IVIG.

It requires GCSF use as well as those holds and also infection prophylaxis.

So that's a quick summary of cell mods, trying to explain it as simply as possible, as well as explaining some of the side effects that are related to cell mods.

That's what I have for this week.