Is there a role for transplant if not used upfront or a second transplant at first relapse?

Is there a role for transplant if not used upfront, or a second transplant at first relapse.

In terms of the use of transplant in the non upfront setting, we are using transplant more often these days. Traditionally when we do the initial stem cell collection, we try to get more than enough for one transplant. And typically what we'll discuss with patients is that because myeloma for the vast majority of people with their initial therapy is not cured.

You want to maintain as many treatment options as possible. And in the future, another transplant might be relevant. And because of that, we try to collect sufficient cells for more than one transplant, optimally up to 2 to 3 depending on a patient's age. Now, there have been questions over the years about the use of the stem cells that are stored and how often they're actually used.

previously there have been reports saying that stem cells are actually underutilized. And I think one of the reasons for that is people don't actually think about doing transplant in the relapse setting. now, in the more recent era with all the newer therapies, and understandably, because a lot of these require less time, commitment and are given as an outpatient.

What we've seen more recently, however, is that as patients go through various therapies, if their myeloma continues to come back, we have actually been using transplant for two different reasons. One is it's used to, control the myeloma and hopefully get a good response. But we understand that, especially if it's used in the relapse setting, that the duration of the response might not be as long as with an upfront transplant.

And so because of that, our strategy generally has been to use an auto transplant as a bridge to next therapy. And oftentimes when people have disease, that's, come back many times. That becomes a key issue in that, we're trying to maximize the time of response. But how we can do that best can change from case to case.

And so the strategy for us has been do the transplant, try to get good control of the myeloma. And as soon as they have recovered from the transplant to come in with the next line of treatment to maintain a good response. the other thing is that patients who have myeloma that's come back many times, if they've gone through many treatments, their bone marrow can become a little bit beat up, and that can affect their blood counts.

And patients who have persistently low blood count sometimes cannot get their treatments on the scheduled basis that we would like to try to get the best response possible. So the other utility of doing a transplant in the setting of relapse, especially if someone has poor blood counts, is that we can improve blood counts after the transplant and then that would also allow for more consistent treatment after that.

How many stem cells are needed for a transplant?

Well, I think that if one is having a comprehensive discussion with their transplant doctor, the key question is how many cells? Well, the basic question is how many cells do I need to be able to do one transplant. And the the general guidelines across the world basically is that you need at least a minimum of 2 million stem cells based on your body weight.

and then anything beyond that is considered extra. But again, getting back to the idea that, when we do transplant, we do like to have extra cells for the future. We at Memorial, we typically aim to get anywhere between 6 to 10 million stem cells. And then again, that the reason for doing that is that you would have stem cells for more than one transplant.

And then the other issue is that although 2 million is the minimum number, optimally, if we can, we do like to give a higher dose of stem cells with the transplant, because then that translates usually into a quicker recovery of a person's blood counts.

Is there a downside to collecting too many stem cells?

The only potential downside would be if someone is having a difficult time in terms of side effects from the medications that are used to get the stem cells to come out of the bone marrow and into the circulating blood. So we typically we use two, two different, medications that are both injections. One is called neupogen The other is called the mozobil.

And they work in slightly different ways to help release the stem cells from the bone marrow into the into the blood. one of the more common side effects from that process is having bone discomfort or pain. So you can imagine if someone is having a lot of achiness or overt pain, then that can make the process more difficult.

And you wouldn't want to necessarily keep going to try to get more stem cells in that in that case. So it really depends on the side effects that someone is experiencing as they go through the collection process. Sometimes people have no side effects and they're able to sail through. the other thing is that when an individual is collecting stem cells, how how many we can get and how quickly we can get them varies from person to person.

So sometimes people will finish their collection and we'll get more than 10 million cells in one session. in contrast, sometimes people require up to four days of consecutive collections and still just barely get to 2 million. So that can also take a toll on someone, because as each day passes, when you're undergoing collection, that does tend to increase fatigue and some other side effects that are associated with the collection process.

So certainly, I think the data suggests that early transplant versus late transplants approximately the same. And so for some patients, you can actually say, all right, if you don't want to be transplanted. And the field's actually changing quite a bit. also at the same time that you can wait and get transplanted later. Now let me back up and say that the way that I think about transplant is not the transplant part.

The way that I think about transplant is its ability to give a whole lot of chemotherapy to somebody. So this is high dose chemotherapy. And it just happens that you need a transplant to actually make it through that high dose chemotherapy. So what we're really looking at is what is the role of high dose chemotherapy in the management of a patient.

And certainly that there is some evidence that, you know that you can you can actually do high dose chemotherapy after somebody begins to relapse. And so you can wait on transplant. There's certainly evidence. And it may be that in you know, there's certainly evidence that if you do that high dose chemotherapy as part of the original treatment, you may get better outcomes.

so and I think it depends on the kind of patient. So for us, we tend to do the transplant as part of the first round of therapy or the first sequence of therapies in younger people. because what we're trying to do is actually not have them ever relapse. And then for older patients that may have other medical problems.

It makes sense to sort of delay the transplant. You might not need it. or those patients may go eight years on their current therapy, and you may never need the transplant and expose them to the high, you know, the risk of the high dose chemotherapy where we use second, transplants really are people that did really well with their first transplant.

So if somebody got a high dose chemotherapy and they went four years or eight years without relapsing and then they relapsed. It makes us think, maybe we can go ahead and try that high dose chemotherapy transplant again, get good responses out of that. On the other hand, if somebody gets high dose chemotherapy and a transplant and then relapses within six months or 12 months, we say, that didn't work.

I mean, that is I'll be showing that the myeloma is resistant to that high dose of chemotherapy. So treating that patient again with another block of high dose chemotherapy is probably not going to be effective.

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