EHA 2023 | Key myeloma highlights from EHA 2023

We are here in the EHA 23 in Frankfurt. And I want to ask you Jesus about the, I think the most relevant recent data we have on myeloma, which is the data on the CARTITUDE-4 with cilta-cel in early relapses. Okay, I think, I think this is an important trial because there is an unmet medical need in those patients that relapse early on and are refractory to lenalidomide. And in these patients the medium progression-free survival is relatively short and probably is going to be even worse if they are also refractory to daratumumab. Therefore, we need something special for them. And what has been done in this clinical trial was to compare cilta-cel versus standard of care. And at that time, we were talking about 2022 there were only two possibilities abilities dara-PD or PVD. And based on this comparison in more than 400 patients randomized one or the other, what we have seen is a 74 reduction in progression or death in the experimental arm. And also I think in this study, what we have seen is that we are confirming the efficacy of cilta-cel in the CARTITUDE-1 that was for the latest stage of treatment and here is superior because is used in early lines of therapy. But also the safety profile is probably a bit better when you open using in early lines. And Enrique, let me let me ask you also regarding this clinical trial because I think it’s going to be approved this CAR T, cilta-cel, in late lines of therapy. But we are facing more and more commonly patients that relapse after frontline refractory to dara and len, then do you think is really a need for the near future.

Absolutely. I think that now we are facing us to say more double and particularly triple-class refractory; patients refractory to PI, IMiDs and anti-CD38 monoclonal antibodies after one or two prior lines of therapy because we are using all these lines of these therapies very early in the disease. So we need novel agents for them. And definitely, I think all these novel immunotherapies with CAR-Ts and bispecifics are really something that is a breakthrough for these patients. I think we need to move them earlier. We don’t have to wait for 3-4 lines of therapy as soon as possible. We have to have these agents for them. And definitely CAR-Ts are perfect.

Probably I can add something in line with what Enrique has mentioned is that in this study, if we look to the progression free survival in the control arm, it was 11.8 months. But now we have in this in the experimental arm is 76% progression free. And if we concentrate in those patient that actually received the CAR T is 84% 85% therefore this means that the majority of the patients are progression free at one year and I expected that is going to be probably a plateau in those that achieve MRD negative status. I mean, it’s very early think that, but let’s look for the near future. And I don’t know if you have there is data on the trial on quality of life of the patients probably there is not yet. But I really think that also having the CAR T with this one shot and then being out of treatment for, I would say, even say, I was going to say forever, but it’s until progression. But this for a long time, it’s also really something completely new for these patients.

Yeah, I mean, it will go back to the CARTITUDE-1, it was reported at the last ASCO, a median progression free survival of three years. Then if you multiply this and without any treatment for this period of time, I think we are now opening a new paradigm for myeloma patients. I want also because I briefly mentioned Enrique about the minimal residual disease. If again, if we look to the CARTITUDE-1, but it’s the same here in, in CARTITUDE-4, the patients that achieve an MRD negative status. Do you think, are we going to cure some patients?

Well, I think, I really, if the question is, if I think that I really believe we are curing patients. So I think these trials are really something completely different. We have so many patients in MRD negativity in late lines of the disease that of course, if we move to the first relapses and even now we are using them in newly diagnosed, the rate of MRD negativity is very deep, MRD negativity is really high. I definitely think we are curing patients. Now, I have to say my nurses, my resident physicians that when we see these type of patients that are MRD negative after several lines of therapy, I have to say this is not, this was not normal three years ago, this is something absolutely revolutionary having these patients so well with these deep responses lasting for so long. I really think enrique, this is going to be a bit dangerous, not, not for me, because if we are curing myeloma, probably I’m not going to have any problem in the near future with my myeloma dedication. But for people like you similar to what happened in the past with the CML, you will need to reinvent yourself.

I don’t know, but maybe we will have, I think you still have my, we are now in the middle of the revolution of this (inaudible). Still we need to how to best use them if we have to use some immune some maintenance approach is if we can do these agents in combination. So I still have, we still have a lot of, a lot to know. But yes, maybe in 5, 10 years, we’ll have to move to another disease to try to find something new.

This will be in fact, this will be marvelous because I mean, we are working for patients and this morning we have the IMS and EHA combined meeting. The first talk was about minimal residual disease. And now it’s clear that minimal residual disease can help physicians in many ways to adapt treatment when you have early refractory disease to try to stop treatment during maintenance for those patients that may not need. And you will avoid refractoriness You can also evaluate the efficacy of the different treatment arms in clinical trial. Therefore, I think this is a new tool that is going to be in the clinic.

Absolutely. So I think sometimes some years ago, we have the MRD only as a prognostic but only it’s very important. It’s a prognostic information. But now more and more we are using MRD as a guide to the take decisions, to take clinical decisions and to know how best to treat our patients. And this is for me is also something very probably we will need to stop at some time because you know, Enrique and me, we have been working now for many years together and we can continue talking and for the audience I think is now time, yes to stop and to say, thank you very much to all of you.

Okay, thank you. And we go into the meeting.