When are tandem or allogeneic transplants considered?

When people talk about induction therapy, they're usually referring to the most commonly used treatment approaches. But there are other less frequently used options that may come up in certain situations. In this video, we'll take a closer look at tandem transplants and allogeneic transplants, two approaches that aren't typically part of standard induction therapy, but may be considered for select patients.

What are tandem transplants? And are they used as part of induction therapy?

Tandem transplant is actually when you have two autologous stem cells transplants back to back. And it's typically done in a planned fashion. So, a patient will undergo an initial autologous stem cell transplant. And then once recovered from that first transplant goes into a second transplant.

The idea here is that if Melphalan or high dose chemotherapy is good at knocking down myeloma, that two transplants is even better.

And so, prior to the era of our modern myeloma medications, it's something that was done not, infrequently. I think that now that we have drugs that are very effective, like the immunomodulatory drugs like lenalidomide or the proteasome inhibitors, and now Cd38 monoclonal antibodies, the question is, do we need to do it as much?

And I think the data kind of we'll see different types of data. For instance the European data suggests that for patients who are treated that have high risk cytogenetics, like 4;14 translocation or 17P deletion, that they benefit from tandem transplant. But we have to remember that their initial therapy was vmp VELCADE Melphalan prednisone or something like that.

And so, when we try to look at U.S. data where patients are receiving RVD, more standard initial therapy and then having tandem transplants, initially there was also a thought that there was benefit.

However, this was followed by lenalidomide maintenance.

In the stamina study, researchers looked at whether doing one stem cell transplant, two stem cell transplants back to back, or one transplant followed by extra treatment led to better outcomes for people with multiple myeloma. When they analyzed everyone as originally assigned to treatment, this is called an intent to treat analysis, there was no meaningful difference in how long people lived without the disease getting worse or an overall survival.

No matter which approach was used. This was true for the overall group of patients, including those with standard risk and high risk myeloma. However, among patients with high risk myeloma, often defined by certain chromosome changes, those who received two stem cell transplants appeared to stay in remission longer. About 44 out of 100 high risk patients who had a tandem transplant were still in remission six years later, compared with about 32 out of 100 patients who did not.

So we don't treat high risk patients like that exactly anymore. Right. We treat them with quadruplets in the upfront setting and auto transplant followed by combination maintenance at least lenalidomide.

And now we're using more len plus dara. And in high risk patients lenalidomide plus proteasome inhibitors.

And so I just saw retrospective data published by the Canadian Registry suggesting that in this era of effective maintenance therapy that tandem transplants don't offer that same progression free survival or overall survival benefit that we saw in prior data using older drug regimens in the upfront setting.

For patients with high risk disease, a discussion with the treating physician about the potential risks and benefits of tandem transplantation remains advisable, as some centers continue to use this approach in selected cases.

How should response to the initial transplant inform decisions about a second transplant?

Now, if somebody had an initial transplant and didn't go into a deep response, I would be surprised if they went into deep response with a second transplant.

And so sometimes if I think about a tandem transplant, I think if somebody had a great response to the first transplant, but not deep enough, that might be where you might have historically thought about doing a second transplant.

Now we might just reach for a different treatment option, like different myeloma medications, to try to deepen the response.

There might be a scenario where somebody has an initial transplant, still has stem cells in reserve, and might have a second transplant down the road.

These, are being done, I think, less and less frequently for the same reasons of newer, more effective anti myeloma therapies.

But it's certainly an option, especially if someone had a long duration of response with the first transplant, maybe 3 to 5 years or something like that, then that might be someone who benefits from a second one down the road.

But I would say that that's becoming less and less frequent now.

Who should consider a tandem transplant?

I think the ones that come to mind are our high risk patients. Like everything.

Anything we could do to prolong their disease control, I think, is on the table.

Should younger patients consider a tandem transplant?

I think certainly the younger patients are going to be the ones that tolerate it the best. However, the other kind of competing thing that comes into mind when I think about that much Alkylator chemotherapy in a young patient is the risk for secondary cancers down the road.

So, any time somebody is exposed to Alkylator chemotherapy, there's a higher risk for developing leukemia or bone marrow failure or some other malignancy that's secondary to that.

And we think that risk is increased with a second transplant. So for our younger patients that is something that we consider in the, you know, in our decision making.

What is an allogeneic transplant and when is it considered as part of induction therapy?

Just to start out with what an allo transplant is. So when we're talking about an allogeneic stem cell transplant, this is when we actually don't take stem cells from our own cells. But we find a donor. Usually it's a sibling or, maybe someone from the marrow registry that matches, certain markers so that your body doesn't reject it and, develop reactions to the donated stem cells the way that it differs from autologous stem cell transplant is autologous stem cell transplant is a way for us to safely deliver high dose chemotherapy.

So the purpose of auto transplant is high dose chemotherapy against the myeloma. Allo transplant’s totally different. So the purpose of an allo transplant is to use somebody else's immune system to attack your cancer cells.

What is the graft versus myeloma effect?

The benefit is not in the chemotherapy that you get to suppress your immune system. The benefit is getting those donor, transplanted cells, stem cells. It's actually effective in myeloma.

So it's almost like taking on an additional, problem or additional disease in addition to the cancer itself.

What are symptoms of graft versus host disease?

So I would say commonly these symptoms are really mild and manageable. For instance, they might affect the eyes. And you have to use steroid eye drops or maybe mouth where you have to use steroid mouthwashes. Frequently, it can affect the GI tract causing things like diarrhea or elevated liver enzymes, but long term can lead to things like joint aches or pains, prolonged increased risk for infection.

In the era of like current myeloma therapies, most patients that have active or chronic graft versus host disease, there's a lot of caution when it comes to using our newer therapies, like Car-T cell bispecific antibodies, for fear that we might make things worse.

And so, I would say prior to, Car-T cells, when we, you know, we're really limited to proteasome inhibitors, IMiDs, and cd38 antibodies.

We were reaching for allogeneic transplant more frequently now that we have Car-T cells and bispecific and so many newer medications coming down the, pipeline. Allogeneic transplant is not really a common treatment option for myeloma patients.

Is there an increased risk of mortality with allogeneic transplant?

Allogeneic transplant does come with an increased risk for mortality compared to auto transplant.

For auto transplant, the mortality rates are less than 1%, generally.

For allogeneic transplant, that number is higher. I want to say like ten, 20%, again, because of the risk for infection and other transplant related toxicities.