CD19 molecule

This is the time to think about other more definite options which have higher efficacy and higher duration of response.

So what comes to mind would be CD19 CAR T-cell therapy, would be CD20 bispecific T-cell engages, clinical trials wherever there is going to be value there if patient is eligible.

Pertobrutinib, non-covalent BTK inhibitors.

But I think in 2026, the landscape has really moved further because now we also have BCL-2 inhibitor, syndrotoclax.

So usually what I do for my patients who are progressing on BTK inhibition with mantle cell lymphoma, I usually start them on a, if a clinical trial is not available, I start them on Pertoclutinib.

In my high-risk subset, I know that that may not be working for too long.

So I'm planning the next steps like getting them to CD19 CAR T-cell therapy or a clinical trial.

In Waldenstrom's marginal zone follicular lymphoma, I think the next treatment on progression really depends on the duration of prior benefit, the deceased tempo, refractoriness to prior treatment, or is it just intolerance, patient frailty, and then available clinical trials.

I would say we can think about Kite as maybe a nice example of how a company in this space is iterating on the current standard of care.

In the CD19, the large cell lymphoma space, AxiCell was, I think, one of the first, if not the first, CD19 CAR to come to market in large B-cell lymphoma.

The co-stimulatory domain is CD28, so it has rapid in vivo expansion.

At the peak of expansion, we see high rates of CRS and neurotoxicity.

Their second generation that's now in clinical trials, it's a different construct.

It has the CD28 for CD19, but it has a 401BB construct for the CD20 arm of it.

What they've seen so far is a significant improvement in the toxicity profile of that drug, and the responses, at least in the very early data, look at least as good as the the prior iteration.

With that, they have a little bit different, they've adjusted their manufacturing, so they've shortened the amount of time that the cells are, it's a more naive T cell population, so the cells are, the manufacturing time is reduced by a few days, and Kite already has some of the best, in my opinion anyway, the best manufacturing efficiency of anyone in the industry.

Bristol didn't use that language.

No, Bristol paused enrollment in the autoimmune trials of Zolacel, its CD19-targeted CAR-T, and called the events transient and reversible.

Out of an abundance of caution, it had already reported one case of the same syndrome in a Phase I study back in February.

TradePress counted three deaths in CAR-T trials.

The other big news this week was...

the announcement that both Novartis and BMS stopped their CD19 CAR T-cell therapy trials temporarily.

The Novartis trial was put on hold because of concerns on three deaths with their CAR T cell called RAP cell.

They had three deaths related to basically a hemophagocytic syndrome related phenomenon.

BMS is a different story.

They had no deaths.

They had actually suspended their trials a little while ago, but it just got announced at the same time as these folks because they had noted the occurrence of what they call transient and reversible inflammatory events with their CD19 CAR T-cell therapy called ZolaCell, BMS 986353.

Through an abundance of caution, they're doing analysis.

In your discussion in your paper, you bring up a really interesting point and topic based off the data in your manuscript.

I'm going to quote you, in the interest of navigating the landscape of MG treatment, finding of comparable treatment effects is encouraging given the substantially lower treatment burden associated with CD19 B-cell depletion.

How does this change clinical practice? We think of FCRNs as potentially second-line or some people consider first-line.

Should CD19 be the second-line therapy after standard treatment? Or how should we start thinking about all the different options that we have?

line or second line because I feel in myasthenia, the treatment landscape is rapidly changing.

And what we used to have as the traditional therapeutic approach for myasthenia is probably not going to remain the same, maybe even in just next two to three years, right? So instead of going first line and second line, it is important to consider that these medications are efficacious and each of them can have individual merit.

One merit you just mentioned, the CD19 depletion, has ease of administration, meaning you require less frequent administration.

On the other hand, for FCRN inhibitors, you may require more frequent administration.