Is upfront ASCT always preferred or should it be done at first relapse?

Is upfront ASCT always preferred or can ASCT be done at first relapse?

Stem cell transplant still has a role. And when you compare it to no transplant, you obviously have great advantage both in terms of response, in terms of duration of remission, in terms of overall survival, life expectancy. But the question about upfront versus delayed transplant. And there one can come up with the argument that, well, even if I delay the transplant and studies have been done that are two large a randomized trial. One early on in 1998, had a French group and the second one in 2017. But the other French group. But by incorporating all the newer treatment and they both more or less showed similar results that with upfront stem cell transplant versus delayed transplant, more patients achieved complete remission. So depth of response is there with upfront transplant versus delayed transplant. Number two, progression free survival is longer with upfront transplant, but overall survival was about the same. But then, especially in the more recent trial, given the effective treatment for myeloma, we may want to wait a little longer before we say that overall survival is about the same. But one can make an argument for a delayed transplant that while I would rather delay treatment to later, but my counterargument to that would be that if your intent is to achieve the deepest and the most durable remission. Then this upfront is the time, because we know that with modern treatments based on some of the recent trials, the first remission can last on average between five and a half to six years. And it could be much longer in patients who have deeper remission or who do not have high risk chromosomal abnormalities. So you achieve a deep and durable remission, post-transplant, sure, patients do need treatment, but in this day and age, that treatment is quite manageable. And clinical trials have shown that patients have taken revlimid or lenalidomide for an extended period of time or even high risk patients have taken a proteasome inhibitor, whether it is bortazomib. And now of course more data coming out with ixazomib. So you can do upfront transplant and you can stay on maintenance treatment, maintaining a fairly decent quality of life. And this was shown in actually the French study that was found in the nineties. Some of the other arguments in favor of upfront transplant that I make to my patients also include that you want to get a more intense treatment when you are younger and in better health. Again with time, no one gets younger. And with time of course we can develop other diseases. So later on you may not be eligible for high dose therapy either because of age, because of some other comorbidities that someone develop. Sometimes it's a disease that has become more resistant and you get much less out of that transplant than you would get upfront. So again, it's more of a philosophical argument, but as a transplant and looking at the overall data, I try to convince patients with upfront transplant, but I fully respect someone's decision when they decide to delay it to a later time. The upfront transplant so I always tell patient, it's the one that works the best because the myeloma is a strange cancer as you know is a strange blood cancer because unfortunately even if you go in the in deep commission in complete remission you will eventually come back because the myeloma hides. And and that's the reason why the chemotherapy works, because there is a better penetration. So what's happening when myeloma comes back and I always tell my patients when you relapse post-transplant, you're not going to die of myeloma because we have so many new therapies. Over the last couple of years, many new drugs approved Selinexor, Isatuximab, veliparib, but the CAR-T cell few weeks ago. But you have to start over. And every time, if you look at the durability of response is the first one is the longest, and then you become shorter and shorter until you are not going in remission anymore. So I always back all my money on upfront. I want my patient to achieve the maximum response with good induction. The transplant and that stay there. And I followed them with minimal residual disease sequentially and tried to keep them there in the negativity. So that we know that the transplant, the average is five years. But we do have a lot of patients five, ten years. Sierra Duke started in 99 and I have patients, so they are at the transplant many years ago. So when you do the transplant after, later, it doesn't last as long because now your myeloma is more resistant, is more refractory. So you can use this second transplant. So if your first lasted ten years. You can do the cycle and say, okay, I'm going to make a last little bit last but still a long time, right? Because the rule used to be half of the time and now we can structure with a maintenance. But if your transplant last only a couple of years, the second is not going to last much long. And if you do a transplant the after you fail many lines of therapy is not going to last as long. So it's almost becoming a bridge where you can decrease the myeloma burden, put the patient to get a little bit better and then maybe put in additional therapy in other clinical trial and other therapy. So the approval for a transplant is for, at diagnosis as a consolidation type of therapy to get the disease and as deep as level of remission, whether that be a complete remission or minimal residual disease, negative state, do we commonly do it at first relapse or as a salvage type of treatment in the later lines. We have done it, but preferentially doing it that first time or as a first consolidation will really get you the most benefit. In the era of novel immunotherapy such as CAR-T. We certainly haven't had a study that looks at or we have some now that are upcoming looking at CAR-T and transplant or CAR-T post-transplant. But, we can't say at this point that CAR-T will take the place of a transplant. We don't have enough data for that. If you're leaning towards a transplant, get the transplant done sooner rather than later. If you have issues and everybody has sort of life related issues, have that discussion, have those stem cells in the bank and certainly waiting on the transplant and getting it right at a time which is convenient is perfectly reasonable. But make sure you have those stem cells in the bank for you. Looking at the progression free survival. One would say that most people will want to do it. We've moved away, though, from three drugs now and be using quadruplets already. So in the context of quadruplets, what we've actually assumed is that transplant should be done in everybody. And we've actually incorporated transplant in all of the clinical trials. In the real world setting when we're seeing such deep responses with quadruplets, a lot of people are deferring their transplant, and there's nothing wrong with that as long as you follow patients closely. So monitoring patients is critical. I think keeping that option as an option to access as and when you need it. And having that conversation with your oncologist is critically important. And then, making that decision on whether you want you're the kind of person who wants it upfront or you're willing to wait on it a little bit is really that's the kind of discussion which needs to be had when we do not see an overall survival advantage.