If I am not eligible for transplant what treatment options should I consider? How effective are these treatments compared to transplant?

If I am not eligible for transplant, what treatment options should I consider?

How effective are these treatments compared to transplant?

A common question we get in the clinic is whether someone is eligible for transplant.

And it's a question that sometimes creates disappointment because I'm not going to be able to go through the transplant.

And varied in that question is an assumption that transplant is the only or it's necessarily the best treatment.

And the short answer to that is no.

I do believe transplant is one of the options, but it's not the only path to move forward with a treatment for myeloma.

And the reason we talk so much about this eligibility or not is that there's no question in my mind that as we go on life, transplant can become a much bigger burden in individuals who are older.

Nowadays, we see most patients in their 65, should consider going through a transplant.

Most patients over the age of 75 probably, should avoid transplant.

And then somewhere between 65 and 75, there's some adaptation based on the fitness and the strength of the person.

But if I were to tell someone, you're not going to be eligible for transplant, what are some of the treatment options?

The short answer is they're actually very good treatment options.

In particular, I think of all the options we have, there's a clinical trial that was called the MAIA clinical trial that looked at the combination of daratumumab lenalidomide, REVLIMID, and dexamethasone.

That trial gave us to what we would describe with superlative terms, great results, because the durability of the control of the disease is quite long with that.

It has been estimated to be over five years.

Since the recording of this video, updated results show that the overall survival was still not reached, with estimated 60 months overall survival rates at 66.6%.

Now, five years is the median. That doesn't mean that someone puts a clock and you get five years. That means that if you take 100 patients at the end of five years, half of those patients would have required a change of treatment, something new.

The other half are still doing very good.

So we like that treatment. It’s simple, as I tell patients, always easier said if you're sitting in the doctor chair but is very well tolerated. It is probably one of the most best already treatments we have and we have seen that it can result in significant prolongation of survival.

We did a study just recently using this big databases, what we call the simulation, where we asked ourselves the questions, if you start with a treatment like this, and then you were to assume that someone who was not transplant eligible worked to get a second treatment with either carfilzomib or pomalidomide estimated that for a patient like that, we would have a median survival that would exceed nine years.

So with that in mind, when I see patients now, if you over 75, I usually will avoid transplant, but I'm even questioning whether we should be doing transplants between 70 and 75.

And I'm a sitting in front of that person. I think if this was my mother and my father, how strong would I be in pushing forward with the transplant and knowing what I know about that study we did? I would say less so.

I think it's reasonable to consider not going to transplant for that patient population.

So hopefully, this provides an explanation of why not necessarily being transplant eligible. It's a terrible thing. It's just a reflective, stance of where we are in life.

Of course, we all want to live to 120, but most of us won't. And that means that if you're 75, let's say, and you start with one of those new treatments, your life expectancy, it's going to be pretty close to normal life expectancy.

So we have good options for those patients.

How is transplant eligibility determined?

As far as the eligibility for transplant, I probably varies by country and program.

And for example, in Europe, there may be age cutoff at age 65 or similar, whereas in the U.S. we don't typically have a specific age cutoff.

I think Medicare may require patients to not be over 80.

Typically, it's very common to have patients that are eligible for stem cell transplant up until 75.

But and when they're between 75 and 80, it's on a case by case basis, depending on their physiologic function and how fit they are.

And if they're not having any frailty issues.

And certainly it's still an option for those patients.

And typically it's going to be if they have organ dysfunction, if they have cardiac dysfunction or lung dysfunction, those patients may be ineligible.

Or if they're more frail, we may not want to do a toxic potentially more toxic stem cell transplant for those patients.

But never fear. We do have excellent options for patients that either don't qualify or don't want to do a stem cell transplant.

We are typically doing anti CD38 monoclonal antibody based front line induction therapy for myeloma these days, whether it's pretransplant or for the non-transplant patients.

If were being aggressive in the patients younger and fit and really definitely wants to go to transplant, we're often doing quadruplets therapy with daratumumab, lenalidomide, bortezomib and dexamethasone prior to transplant and those that are not going to transplant. We will still use daratumumab and combined with lenalidomide and dex triplet therapy.

And those patients, according to the Maia study, have very good outcomes. And about five years into treatment, more than half of them are still in remission even without a stem cell transplant.

The reason that we still do the stem cell transplant when able is that partly because of the determination study recently showed that if we compare patients that had novel therapies for induction and then either go to transplant in first remission or don't do the transplant, the ones that did the transplant and first remission had on average of about 22 months longer remission compared to the ones that did not so close to two years longer, progression free survival or remission, as we call it.

And so, certainly in the patients that can tolerate it, we typically still try to do that.

However, that study did not use daratumumab in the front line setting. And so we don't really have a direct comparison daratumumab based induction therapy with or without stem cell transplant.

And so, those patients in the MAIA study without a transplant are having, five or six years of remission without a transplant.

And the determination with about five or six years of remission.

So they may still have pretty comparable outcomes even without a transplant.

And also those that achieve a molecular or really deep remission after their induction therapy, we might also just collect and store those patients’ stem cells and hold off on the transplant, especially if they're not very excited about going into the transplant as well.

If I am not eligible for ASCT, will that make me ineligible for CAR-T cell therapy?

If you're not eligible for transplant, does that mean you won't be eligible for CAR-T?

And the answer is resoundingly no.

We actually are doing CAR-T on patients who we would traditionally not think of them as being candidates for stem cell transplant patients into their eighties.

In addition to the CAR-T, we have the option of the Bispecifics.

Now, the Bispecifics are very interesting because they provide us a little bit more of a controlled situation.

So as an example, I have patients who have serious medical health issues for other reasons.

An example I can think of as a patient with severe heart disease, coronary disease with heart failure.

And we felt that person was not eligible for transplant, but also we felt that CAR-T may have be tricky because once you do the CAR-T, you're committed for the duration of what the CAR-Ts are.

So in that circumstance, we elected to go first Bispecific because we can't control the situation better.

And I'm happy to report that patient is doing very well.

To learn more about the treatment options discussed in this lesson, go to HealthTree University's course entitled Know Your Therapy and then select the treatment you want to learn more about.