Who is eligible to receive CAR-T therapy?

Who is eligible for CAR-T cell therapy

CAR-T cells, are have been approved in, multiple, settings, for patients with relapsed myeloma.

And initially those products, the two products that are currently available, cilta-cel and ide-cel were available for patients with heavily relapsed myeloma, based on some other trials comparing cilta-cel or ide-cel to some standard regimens that that we would typically use after one or 2 or 3 prior types of myeloma treatment.

Those products were seen to be better than some of the standard treatments we had available and now have been become FDA approved in earlier lines of therapy. So after, one line of therapy, cilta-cel, is has been available and after two or more lines of therapy, ide-cel has become available, for patients generally as a standard of care approach.

So there are efforts to look at, CAR-T cells in earlier, you know, settings, potentially considering some use of CAR-T cells in patients who had completed their initial therapy for myeloma. And an autologous transplant, they'd had an insufficient response, to that whole treatment program.

I know of at least one trial where they are enrolling some patients to consider CAR-Ts after that, but I do see in the future that there will likely be more trials that are including CAR-T cells as part of front line therapy.

But I think we're probably some years away from knowing, how soon patients might be, you know, considering getting access to CAR-T, earlier than their current, FDA approved indications. besides the label indication. FDA eligibility criteria. What other things should be considered before going forward with CAR-T therapy?

CAR-T, is a, type of treatment that can be complex. Can require, lead time for manufacturing requires, close contact with the clinic.

It requires patients to have good fitness.

They should be able to, handle some of the side effects that may come up from, delivery of CAR-T cells, including cytokine release syndrome and the possible, although less common, risk of some neurologic issues with CAR-T.

In general, I think many patients are good candidates for CAR-T. The... we want to make sure they're fit. Their heart, lung, and kidney function are good, that they have a preferably as good an option, to get them with to the CAR-T under good disease control, and that they have, the right support systems in place, after CAR-T to get them through the early post CAR-T period, when they might be more risk of having certain side effects.

So having a caregiver support, and, process in place, being able to get to and from the center is important, at least in our center.

And I know at others, for patients who come from a great distance, they might need to, temporarily relocate to be within a certain radius of, of the center so that if some issue comes out there, they have the ability to get care from the team at the center that has experience with managing the CAR-T related side effects, all of these, you know, really important and complicated factors play a role.

But there are there are many patients who are, good candidates. And I think that, as we get, more experience with CAR-T, and expand our ability to deliver to more patients, I think it's going to be good for, a wider group of people.

So CAR-T cell therapy has been a fantastic addition to our armamentarium against myeloma. But right now, I don't think everyone can get CAR-T cells because of the toxicity piece.

And usually it's patients that have to have a ECOG performance that is 0 to 1. These are patients that are, you know, otherwise doing really well and healthy. I will say that when it standard of care, we have some patients that maybe aren't and that ECOG 0 to 1, maybe two. And again patients whose kidney functions and liver function and heart function are relatively okay.

Because again, it's the toxicity piece.

And hopefully as we learn more and more, we'll be able to get more patients on our clinical trials. There's a, you know, a hard stop in terms of have to have, ECoG and 0 to 1, your platelets have to be greater than 50 to 100. Neutrophil count has to be greater than one.

Your platelets have to be greater than 50. Your, hemoglobin has to be greater than eight. So there's a lot more in terms of eligibility criteria trials, they're a lot more strict.

So both Ide-cel and cilta-cel have multiple, trials that they're looking at different time points. So we're excited about one that's going to come out in Europe, that they're going to look against transplant versus CAR-T for cilta-cel. That'll be really exciting. And then in the US we have trials looking at CAR-T maybe right after transplant.

And so a lot of data hopefully the next couple of years that we'll learn a lot more from.

Besides FDA eligibility criteria, what other factors should be considered when discussing CAR-T treatment?

But in terms of the other, eligibility criteria of how the patient is, whether you think that patient would be eligible for CAR-T or not is based on the patient factors, the disease factors and the treatment related factors.

What I meant to say is that the somebody how old is the patient? How how is the performance status of the patient. You know, what are the other comorbidities the patient has? What kind of disease burden the patient has? Is the disease relapsing very fast or the disease relapsing slowly. And what are the other treatment related issues the patient has or the prior toxicities.

The patient has it the patient has baseline kidney dysfunction and the patient has baseline neurological dysfunction. So these are the that things needs to be factored into account in addition to the eligibility. And what is the label has been mentioned. And that is how we decide the eligibility of the patient for the CAR-T.

Are there any age restrictions that may exclude an individual from CAR-T therapy?

These are by far lower doses of chemotherapy than what we use in transplant conditioning, which also allows us to address the average age group that these diseases are common in.

So we routinely treat with CAR-T cells people older than 70. And we've created a number of patients older than age 80. And the registry data in the United States at least shows that patients up to age 91 have been treated with CAR-T cells. We have no concern in doing this in older individuals, and we do not use age as a barrier or as a parameter for eligibility, or whether it's appropriate to use CAR-T cells

While a patient may be eligible and a good candidate for second line CAR-T, Is it always the right choice for them at that time?

I think this is a really important, you know, cutting edge question of kind of where we are today in the myeloma field. And it's a challenging question.

Certainly, we've seen from, at least in the second line setting, the trial that led to the approval of cilta-cel, CARTITUDE-4 trial showed some great benefits for some of our patients who get CAR-T over the standard available therapies, including, you know, potential.

We know that it, extends the amount of time until the patient needs a different type of mild treatment greatly. And recently, I think the trial had also showed some survival benefits for those patients who got CAR-T. However, CAR-T has some issues with it. There are some, complex side effects and complications that can come from CAR-T that one needs to consider in the risk benefit analysis that each patient and provider must go through to decide whether or not it's the right fit for a patient at that point in time.

Some common issues that can come up with CAR-T, you know, the side effects that happen during the process, like cytokine release syndrome or immune cell associated neurotoxicity syndrome or Neurotoxicity can happen. Those are really short term and likely temporary issues.

However, we've also seen some, more uncommon complications of CAR-T that, are worrisome, including, there's been some rare cases of, more permanent neurologic dysfunction, nerve injury, some rarer cases of, parkinsonism, additionally, second cancers, I think is another major concern that as a more commonly seen issue, I wouldn't say it's common, but I'd say that it's a bigger problem than some of the neurologic concerns although the neurologic concerns are certainly scary.

Myelodysplastic syndrome has been a problem that's been seen in, both using, you know, both of our available CAR-T products likely related to patients prior treatment exposure history to certain types of chemotherapy, as well as potentially some of the chemotherapy that's used for the lympho-depletion to make room in the body for the CAR-T cells.

really the possibility of second cancers, I think as a risk, that is a known problem with CAR-T. And I think that that is something that we need to take into account when deciding whether or not someone should go to CAR-T next. There are other quite rare entities like T-cell cancers that have been seen, but those are really, I think, much rarer entities.

And I think I would say that's probably not a reason not to do it, but, to kind of summarize,

I think, the there's a great promise and there's a lot of positive results that we've seen from use of CAR-T and having more treatment options available to get to CAR-T under better disease control is more easily done in the second line setting.

Then after that, however, the risks of second cancers, the complexity of CAR-T, the need for, you know, hospital admission, taking time out of your life to go through the process,

I don't always think they should, certainly, my patients who have, high risk disease, those patients who, who may have some already have some worrisome signs of an either aggressive type of myeloma, potentially those patients who might have, history of plasmacytomas for example. Those patients worry me.

And those are the people and who are more likely to lean towards doing it earlier rather than later.

But, you know, for those patients who have had, you know, let's say an excellent, you know, response to the initial therapy, what appears to be not a rapidly growing, aggressive, high risk type of myeloma. There are a number of great options for use in second and line therapy that are not CAR-T.

And I think those are still viable choices.

I always just like to try to think a few moves ahead and, to think about where I might be with a particular patient that we're making this decision with. Where are we going to be in the third line setting? What are we going to have available to us?

And that's always an important calculation we need to make to determine, you know, whether it's time to do CAR-T now or whether we should do something else that isn't CAR-T, and consider returning to CAR-T later. And, you know, always, always hard to try to predict the future, but you always want to think about how can I maximize the amount of treatment options that my patient has, to try to, you know, help them get the best outcome possible.

We want to maximize their options. So, in scenarios where I think I might have CAR-T is an option now, but for some patient related reason or some other reason, I might not have access to it later. That might also be a reason why I might think about doing it now. But this is a complicated discussion. I think that we really need to do as best a job as we can to educate the patients about the risks and the benefits of CAR-T, because there are great risks and potential great benefits, both.

But, you know, I think it is a really valuable treatment approach deciding when to do it and when to do it later or not to do it as a complex decision that, it requires, important conversations with our patients that, need to help us get to that conclusion.