Hi, my name is Rakesh Popat.
I'm a hematologist at University College Hospital in London in the UK.
My pleasure to be here at ASH and tell you about my abstract that I'll be presenting on Cartitude-4.

Cartitude-4 was an open label phase 3 randomized clinical trial for patients who had relapsed myeloma, and the patients that were entered were those who had between 1 and 3 previous lines of treatments and had been exposed to lenalidomide and had stopped responding to that.

They were randomized in a 50:50 chance to either receive CAR-T cells, which is cilta-cel, or standard of care. And there's two standard of care options that were available: daratumumab, pomalidomide, and dexamethasone or pomalidomide, velcade, and dexamethasone.

Now, the preliminary results have already been presented for Cartitude-4, which demonstrated that the CAR T-cell, which is cilta-cel, demonstrated a significant improvement in progression free survival as of the time up until you relapse. And indeed an early signal in terms of overall survival.

So how long that you would live for patients who received cilta-cel compared to standard of care. And that's very exciting results.

So what we're now diving into is the minimal residual disease results. So this is looking at the small amounts of measurable myeloma that we would find on a bone marrow biopsy.

And the reason why that's really important is because there's been a lot of work that has correlated minimal residual disease and overall survival. So we really want to understand how the CAR T-cells affect patients for that.

Our patients were very generous. They gave bone marrow biopsy throughout the study. And we were able to look at minimal residual disease. Both had a ten to the minus five level and a very deep level at ten to the minus six.

What we demonstrate is that overall, patients were more likely to achieve MRD negativity with the cilta-cel compared to standard of care.

And what was super interesting was that if you look at the high sensitivity levels at ten to the minus six, most patients are achieving MRD at that level with CAR-T, but they weren't achieving that with standard of care.

So the take home message is that you're more likely to have a very deep and MRD negative response with CAR-T compared to the standard of care.

The last thing we looked at was something called sustained MRD negativity, which is if you are able to maintain that level of MRD negativity for 12 months or more, and that has previously been correlated with a better survival outcome.

And sure enough, we found that patients with cilta-cel had longer levels of MRD negativity that was sustained compared to those that didn't. And we also demonstrated that those patients had better fitness of their T-cells and also had a better disease response and a better CAR-T expansion than others.

So overall, I think all this correlative data really does support the use of cilta-cel, which is a BCMA targeted CAR-T for patients that early as second relapse better than standard of care.